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Anoikis, a form of programmed cell death induced by loss of cell contact, is closely associated with tumor invasion and metastasis, making it highly significant in lung cancer research. We examined the expression patterns and prognostic relevance of Anoikis-related genes (ARGs) in lung adenocarcinoma (LUAD) using the TCGA-LUAD database. This study identified molecular subtypes associated with Anoikis in LUAD and conducted functional enrichment analyses. We constructed an ARG risk score using univariate least absolute shrinkage and selection operator (LASSO) Cox regression, validated externally with GEO datasets and clinical samples. The clinical applicability of the prognostic model was evaluated using nomograms, calibration curves, decision curve analysis (DCA), and time-dependent AUC assessments. We identified four prognostically significant genes (PLK1, SLC2A1, CDKN3, PHLDA2) and two ARG-related molecular subtypes. ARGs were generally upregulated in LUAD and correlated with multiple pathways including the cell cycle and DNA replication. The prognostic model indicated that the low-risk group had better outcomes and significant correlations with clinicopathological features, tumor microenvironment, immune therapy responses, drug sensitivity, and pan-RNA epigenetic modification-related genes. Patients with low-risk LUAD were potential beneficiaries of immune checkpoint inhibitor (ICI) therapy. Prognostic ARGs' distribution and expression across various immune cell types were further analyzed using single-cell RNA sequencing. The pivotal role of CDKN3 in LUAD was confirmed through qRT-PCR and gene knockout experiments, demonstrating that CDKN3 knockdown inhibits tumor cell proliferation, migration, and invasion. Additionally, we constructed a ceRNA network involving CDKN3/hsa-miR-26a-5p/SNHG6, LINC00665, DUXAP8, and SLC2A1/hsa-miR-218-5p/RNASEH1-AS1, providing new insights for personalized and immune therapy decisions in LUAD patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Radiation pneumonia is a common adverse reaction during radiotherapy in lung cancer patients, which negatively impacts the quality of life and survival of patients. Recent studies have shown that compound Kushen injection (CKI), a traditional Chinese medicine (TCM), has great anti-inflammatory and anticancer potential, but the mechanism is still unclear. We used CiteSpace, the R package "bibliometrix," and VOSviewers to perform a bibliometrics analysis of 162 articles included from the Web of Science core collection. A network pharmacology-based approach was used to screen effective compounds, screen and predict target genes, analyze biological functions and pathways, and construct regulatory networks and protein interaction networks. Molecular docking experiments were used to identify the affinity of key compounds and core target. The literature metrology analysis revealed that over 90% of the CKI-related studies were conducted by Chinese scholars and institutions, with a predominant focus on tumors, while research on radiation pneumonia remained limited. Our investigation identified 60 active ingredients of CKI, 292 genes associated with radiation pneumonia, 533 genes linked to lung cancer, and 37 common targets of CKI in the treatment of both radiation pneumonia and lung cancer. These core potential targets were found to be significantly associated with the OS of lung cancer patients, and the key compounds exhibited a good docking affinity with these targets. Additionally, GO and KEGG enrichment analysis highlighted that the bioinformatics annotation of these common genes mainly involved ubiquitin protein ligase binding, cytokine receptor binding, and the PI3K/Akt signaling pathway. Our study revealed that the main active components of CKI, primarily quercetin, luteolin, and naringin, might act on major core targets, including AKT1, PTGS2, and PPARG, and further regulated key signaling pathways such as the PI3K/Akt pathway, thereby playing a crucial role in the treatment of radiation pneumonia and lung cancer. Moreover, this study had a certain promotional effect on further clinical application and provided a theoretical basis for subsequent experimental research., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Competing interests: The authors declare no competing interests. Consent for publication: All the authors declare their consent to publication., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Non-small-cell lung cancer (NSCLC) is the most prevalent type of lung cancer, and there is an urgent need for developing novel therapies. Sonodynamic therapy exhibits exceptional tissue penetration and minimal harm to healthy tissue, making it extremely promising for cancer treatment. The efficacy of SDT is limited by the intricate immunological microenvironment and the resistance to tumor treatment. This study developed targeted nanoparticles that use ultrasound to concentrate on treating NSCLC. The hybrid targeted nanoparticles utilize gold nanoparticles as their fundamental component, with the outside modified with engineered macrophage exosomes and the aptamer S11e to specifically target NSCLC. Ultrasound could effectively eliminate tumors in NSCLC cells by destroying lysosomes via targeted nanoparticles. Simultaneously, fragmented tumor antigens could effectively activate dendritic cell cells to recruit T cells. This method has significant efficacy in suppressing the development of NSCLC and exhibits potential for therapeutic application.

Introduction: Blood samples were collected to explore potential serum biomarkers associated with neurocognitive function in small-cell lung cancer (SCLC) patients who received prophylactic cranial irradiation (PCI)., Methods: This pre-specified study included patients with blood samples available, who participated in a phase III trial (NCT01780675). Blood samples were collected before PCI and 3-days post-initiating PCI. Neurocognitive decline was defined as a decrease of ≥ 5 points on total recall in the Hopkins Verbal Learning Test-Revised (HVLT-R) assessed from pre-PCI to 4-months post-PCI. Biomarkers were screened using univariate logistic regression analysis. P < .1 was considered statistically significant., Results: Forty-eight enrolled patients who had blood samples at baseline were included and 27 were available for analysis as the other 21 did not assess neurocognitive function at 4-months. Lower levels of Tie-2 (OR = 0.999, 90% CI 0.998-1.000, P = .062), and higher levels of MIP-1b (OR = 1.022, 90% CI 1.000-1.044, P = .093), CCL-17 (OR = 1.004, 90% CI 1.001-1.006, P = .029), and IL-1α (OR = 1.597, 90% CI 1.077-2.367, P = .05) before PCI were correlated with neurocognitive decline at 4-months. Decrease of VEGF-C (OR = 0.972, 90% CI 0.949-0.996, P = .055), CCL-17 (OR = 0.993, 90% CI 0.988-0.999, P = .036), IL-1α (OR = 0.788, 90% CI 0.635-0.979, P = .071), and VEGF (OR = 0.981, 90% CI 0.965-0.997, P = .051) 3-days post-initiating PCI were also associated with neurocognitive decline at 4-months., Conclusions: Biomarker levels before PCI and changes in their levels 3-days post-initiating PCI may be linked to subsequent neurocognitive decline at 4-months. If validated, these biomarkers could be used to predict the risk of neurocognitive decline and act as a decision aid for personalized PCI in SCLC., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Immune checkpoint inhibitors (ICIs), including anti-programmed cell death protein 1 and its ligand (PD-1/PD-L1) as well as anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4), have been widely used for treating solid tumors. Myocarditis is a potentially lethal immune-related adverse events (irAEs) caused by ICIs therapy. The treatment of steroid-refractory myocarditis is challenging. We reported two non-small-cell lung cancer patients with steroid-refractory myocarditis induced by ICI. The symptoms were not resolved after pulse corticosteroid therapy and subsequent treatment including intravenous immunoglobulin and mycophenolate mofetil. Considering the level of serum interleukin (IL)-6 decreased by > 50% and level of serum tumor necrosis factor-α (TNF-α) increased during the course of the disease, infliximab was used. Myocarditis gradually alleviated after infliximab treatment. The cases revealed that specific cytokine inhibitors have promising roles in the treatment of steroid-refractory myocarditis. Infliximab could be considered for patients with low level of IL-6 and elevated level of TNF-α., (© 2024. The Author(s).)

Background: The recommended first-line treatment for advanced epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) patients is EGFR-tyrosine kinase inhibitors (EGFR-TKIs). BRAF alterations have been identified as resistance mechanisms. We aimed to identify features of and subsequent treatment strategies for such patients., Patients and Methods: We conducted a systematic literature review of NSCLC patients harboring acquired BRAF alterations. Additionally, BRAF-altered NSCLC patients who progressed from EGFR-TKIs at West China Hospital of Sichuan University were screened. Patient characteristics, treatment options, and outcomes were analyzed., Results: A total of 104 patients were included, 2 of whom came from our center. Seventy-five patients (72.1%) harbored BRAF mutations (57 class I mutations, 7 class II mutations, 9 class III mutations, and 2 non-class I-III mutations), and 29 (27.9%) harbored BRAF fusions. Eighteen patients received triple-targeted therapy, including prior EGFR-TKIs plus dabrafenib and trametinib, and 23 patients received other treatments. The median progression-free survival was significantly longer in patients receiving triple-targeted therapy than in those receiving other treatments (8.0 versus 2.5 months, P < 0.001). Similar findings were observed in patients with BRAF mutations (9.0 versus 2.8 months, P = 0.004), particularly in those with BRAF class I mutations (9.0 versus 2.5 months, P < 0.001). A potential benefit was also observed among patients with BRAF fusions (5.0 versus 2.0 months, P = 0.230). Twenty patients (48.8%) experienced adverse events. Dose reduction of RAF or MEK inhibitor was required in five patients (12.2%). Five patients (12.2%) permanently discontinued treatment (three on triple-targeted therapy; one on prior EGFR-TKI plus vemurafenib; one on prior EGFR-TKI plus trametinib)., Conclusions: BRAF alterations, specifically BRAF mutations and BRAF fusions, facilitate resistance to EGFR-TKIs. Triple-targeted therapy is effective and safe for patients with EGFR-mutant NSCLC with acquired BRAF alterations, mainly among patients with BRAF class I mutations and potentially in patients with BRAF fusions., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The presence of distant metastasis at the time of initial diagnosis is a prevalent issue in non-small cell lung cancer (NSCLC), affecting around 30-40 % of the patients. Acidic tumor microenvironment (TME) provides favorable conditions that increase the invasiveness and aggressiveness of NSCLC. The activity of the glycolytic enzyme lactate dehydrogenase (LDHA) increases intracellular lactate accumulation, which creates an acidic TME. However, it is not yet known whether LDHA is involved in enhancing the metastatic potential of NSCLC and if LDHA is a druggable therapeutic target for NSCLC., Purpose: We aimed to investigate the molecular mechanisms underlying the enhanced NSCLC metastasis in acidic TME, and to explore whether sulforaphane (SFN), an active compound in Raphani Semen, can serve as a LDHA inhibitor to inhibit NSCLC metastasis in the acidic TME., Methods: To mimic the acidic TME, NSCLC cells were cultured in acidic medium (pH 6.6), normal medium (pH 7.4) served as control. Western blotting, bioinformatic analysis, luciferase assay and rescue experiments were used to explore the mechanism and investigate the anti-metastatic effect of SFN both in vitro and in vivo., Results: Acidic environment increases the expression of LDHA which in turn increases the production of lactic acid that contributes to the acidity of TME. Interestingly, elevated LDHA expression results from increased c-Myc expression, which transactivates LDHA. c-Myc expression is directly regulated by miR-7-5p. In vitro study shows that overexpression of miR-7-5p reverses the acidic pH-enhanced c-Myc and LDHA expressions and also abolishes the enhanced NSCLC cell migration. More importantly, SFN significantly inhibits NSCLC growth and metastasis by reducing lactate production via the miR-7-5p/c-Myc/LDHA axis. Besides, it also regulates the expressions of monocarboxylate transporter 1 (MCT1) and MCT4 that transport lactate across cell membrane., Conclusions: The miR-7-5p/c-Myc/LDHA axis is involved in the enhanced NSCLC metastasis in the acidic TME. SFN, a novel LDHA inhibitor, reduces lactate production by targeting the miR-7-5p/c-Myc/LDHA axis, and hence inhibits NSCLC metastasis. Our findings not only delineate a novel mechanism, but also support the clinical translation of SFN as a novel therapeutic agent for treating metastatic NSCLC., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier GmbH.)

Background: The prognostic analysis of lung invasive mucinous adenocarcinoma (IMA) is deficient due to the lack of a universally recommended histological grading system, leading to unregulated treatment approaches., Objective: We aimed to examine the clinical trajectory of IMA and assess the viability of utilizing the existing grading system for lung invasive non-mucinous adenocarcinoma in the context of IMA., Methods: We retrospectively collected clinicopathological data from 265 IMA patients. Each case re-evaluated the tumor grade using the following three classification systems: the 4th Edition of the World Health Organization classification system, the International Association for the Study of Lung Cancer (IASLC) grading system, and a two-tier grading system. We performed a comparative analysis of these grading systems and identified the most effective grading system for IMA., Results: The study comprised a total of 214 patients with pure IMA and 51 patients with mixed IMA. The 5-year overall survival (OS) rates for pure IMA and mixed IMA were 86.7% and 57.8%, respectively. All three grading systems proved to be effective prognostic classifiers for IMA. The value of area under the curve at 1-, 3-, and 5-year OS was highest for the IASLC grading system compared with the other grade systems and the clinical stage. The IASLC classification system was an independent prognostic predictor (p = 0.009, hazard ratio 2.243, 95% confidence interval 1.219-4.127)., Conclusion: Mixed IMA is more aggressive than pure IMA, with an OS rate on par with that of high-grade pure IMA. The IASLC grading system can better indicate prognosis and is recommended for lung IMA., (© 2024. Society of Surgical Oncology.)

Lung adenocarcinoma (LUAD) is the most common subtypes of NSCLC. However, the therapeutic effects for LUAD are unsatisfactory at current stage, so it is important to find new molecular targets and therapeutic strategies. circRNAs can regulate the expression of target genes by binding to microRNAs (miRNAs) to form competitive endogenous RNAs (ceRNAs). Therefore, we investigated the functions of circR-4225 in the tumor progression of LUAD and its molecular mechanism in this paper. circR-4225 is up-regulated in LUAD tissues. EIF4A3, a member of the eukaryotic translation initiation factor 4A (EIF4A) family, promotes the expression of circR-4225. circR-4225 acts as a molecular sponge to down-regulate miR-507, which promotes the up-regulation of the expression of its target gene-tumor necrosis factor superfamily member 11 (TNFSF11). Knockdown of circR-4225 in the LUAD cell lines can inhibit cell proliferation and viability, and promote apoptosis of the LUAD cell lines, which can be reverted by inhibiting miR-507 or overexpressing TNFSF11. To sum it up, this study demonstrated that circR-4225 was significantly up-regulated in LUAD tissues, and circR-4225 promoted LUAD progression by sponging miR-507 and up-regulating TNFSF11. This study can provide new molecular targets for early diagnosis and treatment of LUAD., (© 2024. The Author(s).)

Background: Lung adenocarcinoma (LUAD) is a fatal disease with metabolic abnormalities. The dysregulation of S100 calcium-binding protein A2 (S100A2), a member of the S100 protein family, is connected to the development of various cancers. The impact of S100A2 on the LUAD occurrence and metastasis, however, has not yet been reported. The functional mechanism of S100A2 on LUAD cell metastasis was examined in this article., Methods: The expression of TFAP2A and S100A2 in LUAD tissues and cells was analyzed by bioinformatics and qRT-PCR, respectively. The enrichment pathway analysis was performed on S100A2. Bioinformatics analysis determined the binding relationship between TFAP2A and S100A2, and their interaction was validated through dual-luciferase and chromatin immunoprecipitation experiments. Cell viability was determined using cell counting kit-8 (CCK-8). A transwell assay was performed to analyze the invasion and migration of cells. Immunofluorescence was conducted to obtain vimentin and E-cadherin expression, and a western blot was used to detect the expression of MMP-2, MMP-9, GLS, and GLUD1. The kits measured the NADPH/NADP ratio, glutathione (GSH)/glutathione disulfide (GSSG) levels, and the contents of glutamine, α-KG, and glutamate., Results: S100A2 was upregulated in LUAD tissues and cells, and S100A2 mediated glutamine metabolism to induce LUAD metastasis. Additionally, the transcriptional regulator TFAP2A was discovered upstream of S100A2, and TFAP2A expression was upregulated in LUAD, which indicated that TFAP2A promoted the S100A2 expression. The rescue experiment found that upregulation of S100A2 could reverse the inhibitory effects of silencing TFAP2A on glutamine metabolism and cell metastasis., Conclusion: In conclusion, by regulating glutamine metabolism, the TFAP2A/S100A2 axis facilitated LUAD metastasis. This suggested that targeting S100A2 could be beneficial for LUAD treatment., (© 2024 The Author(s). The Clinical Respiratory Journal published by John Wiley & Sons Ltd.)

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths and represents a substantial disease burden worldwide. Immune checkpoint inhibitors combined with chemotherapy are the standard first-line therapy for advanced NSCLC without driver mutations. Programmed death-ligand 1 (PD-L1) is currently the only approved immunotherapy marker. PD-L1 detection methods are diverse and have developed rapidly in recent years, such as improved immunohistochemical detection methods, the application of liquid biopsy in PD-L1 detection, genetic testing, radionuclide imaging, and the use of machine learning methods to construct PD-L1 prediction models. This review focuses on the detection methods and challenges of PD-L1 from different sources, and discusses the influencing factors of PD-L1 detection and the value of combined biomarkers. Provide support for clinical screening of immunotherapy-advantage groups and formulation of personalized treatment decisions., (© 2024. The Author(s).)

Objectives: The expression of serum free light chain (FLC) is abnormal in various diseases, but its role in lung cancer remains unclear. This study aims to investigate the expression and diagnostic value of serum FLC in lung cancer., Methods: A total of 80 lung cancer patients treated at Xiangdong Hospital, Hunan Normal University from January to December 2021 were selected as the lung cancer group. Another 80 healthy individuals undergoing routine physical examinations during the same period were chosen as the control group. General information and serum κFLC and λFLC levels were collected for all subjects. Clinical indicators such as serum carcinoembryonic antigen (CEA), cytokeratin fragment antigen 21-1 (CYFRA21-1) levels, tumor diameter, histological type, TNM stage, and lymph node metastasis status were recorded for lung cancer patients. The expression levels of serum FLC [κFLC, λFLC, and FLC (κ+λ)] were compared between the lung cancer group and the control group. Lung cancer patients were grouped based on gender, age, smoking history, tumor diameter, TNM stage, histological type, and lymph node metastasis to compare differences in serum κFLC and λFLC levels. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic value of serum FLC alone and in combination with other indicators in lung cancer., Results: The expression levels of serum FLC (κ+λ) and κFLC were significantly higher in the lung cancer group than those in the control group (both P <0.001), while there was no significant difference in serum λFLC levels between the 2 groups ( P >0.05). There were no significant differences in serum κFLC levels among lung cancer patients with different tumor diameters, histological types, or TNM stages (all P >0.05); however, serum κFLC levels were higher in lung cancer patients with lymph node metastasis than in those without, with statistical significance ( P =0.033). There were no significant differences in serum λFLC levels based on tumor diameter or histological type (both P >0.05), but serum λFLC levels were higher in stage III+IV and lymph node metastatic lung cancer patients compared to stage I+II and non-metastatic patients, with statistical significance ( P =0.033 and P =0.019, respectively). The area under the curve (AUC) for κFLC and CEA in diagnosing lung cancer showed no significant difference ( P =0.333). The combination of κFLC+CYFRA21-1 had the highest diagnostic efficacy (AUC=0.875) and sensitivity (71.3%). The AUC for the combined diagnosis of κFLC+λFLC+CEA+CYFRA21-1 was 0.915 (95% CI 0.860 to 0.953, P <0.001)., Conclusions: Serum FLC is highly expressed in lung cancer and is associated with its invasion and metastasis. Serum FLC, particularly κFLC, has diagnostic value for lung cancer, and the combined detection of FLC, CEA, and CYFRA21-1 offers the best diagnostic efficacy.

Background: The aim of this study was to compare breast cancer patients with pulmonary oligometastases (POM) and primary lung cancer (PLC) and to assess whether there were differences in clinical features, CT features, and survival outcomes between the two groups., Methods: From January 2010 to December 2021, the clinical records of 437 with malignant pulmonary nodules who had breast cancer patients were reviewed. POM was identified in 45 patients and PLC in 43 patients after the initial detection of pulmonary nodules. The clinicopathological characteristics, CT appearance of pulmonary nodules, and survival of the two groups were compared., Results: Stage II to IV breast tumors (p < 0.001), high pathological grade of breast cancer (p = 0.001), low proportion of luminal-type breast cancer (p = 0.003), and the higher serum CYFRA 21-1 level (p = 0.046) were the clinical characteristics of pulmonary nodules suggestive of POM rather than PLC. The CT features of lung nodules indicative of PLC rather than POM were the subsolid component (p < 0.001), lobulation (p = 0.010), air bronchogram (p < 0.001) and pleural indentation (p = 0.004). Ten-year survival rate for PLC was 93.2%, which was higher compared with 57.8% in those with POM (p = 0.001)., Conclusions: Elevated serum CYFRA 21-1 levels and late-stage breast cancer may be beneficial for the diagnosis of POM. CT imaging appearances of the subsolid component, lobulation, air bronchogram, and pleural indentation increase the likelihood of PLC. Breast cancer patients with PLC presented better survival with attentive monitoring than those with POM., (© 2024 The Authors. Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

Background: Immune checkpoint inhibitors (ICI) combined with chemotherapy are efficacious for treating advanced non-small cell lung cancer (NSCLC); however, the effectiveness of this approach in the malignant pleural effusion (MPE) population is unclear. This study evaluated ICI plus chemotherapy in NSCLC patients with MPE., Methods: Patients from 3 centers in China with NSCLC and MPE who received ICI plus chemotherapy (ICI Plus Chemo) or chemotherapy alone (Chemo) between December 2014 and June 2023 were enrolled. Clinical outcomes and adverse events (AEs) were compared., Results: Of 155 eligible patients, the median age was 61.0 years old. Males and never-smokers accounted for 73.5% and 39.4%, respectively. Fifty-seven and 98 patients received ICI Plus Chemo or Chemo, respectively. With a median study follow-up of 10.8 months, progression-free survival (PFS) was significantly longer with ICI Plus Chemo than with Chemo (median PFS: 7.4 versus 5.7 months; HR = 0.594 [95% CI: 0.403-0.874], P = 0.008). Median overall survival (OS) did not differ between groups (ICI Plus Chemo: 34.2 versus Chemo: 28.3 months; HR = 0.746 [95% CI: 0.420-1.325], P = 0.317). The most common grade 3 or worse AEs included decreased neutrophil count (3 [5.3%] patients in the ICI Plus Chemo group vs. 5 [5.1%] patients in the Chemo group) and decreased hemoglobin (3 [5.3%] versus 10 [10.2%])., Conclusions: In patients with untreated NSCLC with MPE, ICI plus chemotherapy resulted in significantly longer PFS than chemotherapy and had a manageable tolerability profile, but the effect on OS may be limited., (© 2024. The Author(s).)

Objective: The National Central Cancer Registry estimates the number of new cancer cases and deaths in China in 2022, using incidence and mortality data collected by the National Cancer Center. Methods: According to the data of 700 cancer registries in 2018 and the data of 106 cancer registries from 2010 to 2018, the age-period-cohort model was used to estimate the incidence rate and mortality rate of all cancers and 23 types of cancer in 2022, stratified by gender and urban and rural areas. We estimated the number of new cancer cases and deaths in China in 2022 based on the estimated rate and population data in 2022. Results: The estimated results showed that in 2022, there were approximately 4 824 700 new cancer cases in China (2 533 900 in males and 2 290 800 in females), with an age-standardized incidence rate of Chinese population (ASIR) of 208.58 per 100 000 (212.67 per 100 000 for males and 208.08 per 100 000 for females). Approximately 2 903 900 new cancer cases occurred in urban areas, with an ASIR of 212.95 per 100 000. It was estimated about 1 920 800 new cancer cases in rural areas, and the ASIR was 199.65 per 100 000. The top five cancers (lung cancer 1 060 600, colorectal cancer 517 100, thyroid cancer 466 100, liver cancer 367 700 and female breast cancer 357 200) accounted for 57.4% of all new cases. The estimated number of deaths from cancer in China in 2022 was 2 574 200 (1 629 300 in males and 944 900 in females), with an age-standardized mortality rate of Chinese population (ASMR) of 97.08 per 100 000 (127.70 per 100 000 in males and 68.67 per 100 000 in females). The number of deaths from cancer in urban and rural areas was about 1 400 600 and 1 173 400, with the ASMR of 92.37 and 103.97 per 100 000 in urban and rural areas, respectively. The top five leading cause of cancers death (lung cancer 733 300, liver cancer 316 500, gastric cancer 260 400, colorectal cancer 240 000 and esophageal cancer 187 500) accounted for 67.5% of all cancer deaths. Lung cancer ranked first in the incidence and mortality in men and women. The incidence rate in urban areas was higher than that in rural areas, while the mortality rate was lower than that in rural areas. Conclusions: The burden of cancer in China is still relatively heavy, with significant differences in cancer patterns in gender, urban-rural, and regional. The burden of cancer presents a coexistence of developed and developing countries, and the situation of cancer prevention and control is still serious in China.

Non-small cell lung cancer (NSCLC) is one of the malignant tumors with high morbidity and mortality worldwide. Ferroptosis is a new type of programmed cell death caused by abnormal accumulation of iron-dependent reactive oxygen species (ROS) leading to lipid peroxidation. It involves the balance between iron metabolism, lipid metabolism, oxygen free radical reaction and lipid peroxidation. Recent studies have found that ferroptosis is closely related to the occurrence and development of NSCLC. Due to the emergence of chemotherapy resistance and radiotherapy resistance in the treatment of NSCLC, there is an urgent need to develop new effective drugs and treatment strategies. Traditional Chinese medicine has unique advantages in the prevention and treatment of NSCLC due to its multi-targets and minimal side effects. In this review, we summarize the mechanism of ferroptosis in NSCLC, and discuss the research status of active ingredients of traditional Chinese medicine, single-herb traditional Chinese medicine and Chinese herbal compounds in the intervention of NSCLC through ferroptosis, in order to provide a new theoretical basis for the research of ferroptosis pathway and the prevention and treatment of NSCLC by targeted ferroptosis of traditional Chinese medicine.
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Background: Several studies have indicated that intrapleural infusion of bevacizumab is an effective treatment for non-small cell lung cancer (NSCLC) with malignant pleural effusion (MPE). However, the impact of bevacizumab administered through an indwelling pleural catheter (IPC) on the prognosis of these patients is unknown., Methods: Consecutive advanced NSCLC patients with symptomatic MPE receiving an IPC alone or bevacizumab through an IPC were identified in a tertiary hospital. The patient characteristics and clinical outcomes were collected., Results: A total of 149 patients were included, and the median age was 60.3 years. Males and nonsmokers accounted for 48.3% and 65.8%, respectively. A total of 69.8% (104/149) of patients harbored actionable mutations, including 92 EGFR-activating mutations, 11 ALK fusions, and 1 ROS1 fusion. A total of 81.9% (122/149) of patients received IPC alone, and 18.1% (27/149) received bevacizumab through an IPC. The incidence of spontaneous pleurodesis during the first 6 months was greater in the bevacizumab-treated group than in the IPC-treated group in the subgroup with actionable mutations (64.3% vs. 46.9%, P = 0.28). The median overall survival (OS) in patients with actionable mutations treated with bevacizumab through an IPC was 42.2 months, which was significantly longer than the 26.7 months in patients who received an IPC alone (P = 0.045). However, the median OS did not differ between the two arms in the subgroup without actionable mutations (10.8 vs. 41.0 months, P = 0.24). No significant difference between the bevacizumab through an IPC group and the IPC group was detected in the number of participants who had adverse events, either in patients with actionable mutations (14.3% vs. 8.4%; P = 0.42) or in patients without actionable mutations (16.7% vs. 12.8%; P = 1.00)., Conclusions: Bevacizumab through an IPC resulted in a significantly improved prognosis for NSCLC patients with MPE and actionable mutations. However, patients without actionable mutations do not benefit from bevacizumab through IPC., (© 2024. The Author(s).)

Background: Many clinical trials have shown that postoperative adjuvant chemotherapy can provide a survival benefit for patients with stage IB non-small cell lung cancer. However, whether adjuvant chemotherapy should be routinely given after surgery remains controversial. Therefore, we performed a meta-analysis to investigate the efficacy of adjuvant chemotherapy versus surgery alone for stage IB non-small cell lung cancer (NSCLC)., Methods: Relevant retrospective studies or randomized controlled trial comparing the efficacy of postoperative adjuvant chemotherapy versus observation on the survival outcomes of NSCLC patients up to October 30, 2023 were searched in PubMed, Web of Science, EMBASE, Cochrane Library, VIP database, Wanfang database, and China National Knowledge Internet database. Patient survival data, population characteristics, and other relevant information were extracted, and data were analyzed using Review Manager 5.4. The primary endpoints included overall survival, disease-free survival, and recurrence-free survival., Results: A total of 13 randomized controlled trials or cohort studies including 19,442 patients were included. The results of the meta-analysis showed that postoperative adjuvant chemotherapy in patients with stage IB NSCLC had better overall survival (odds ratio [OR] = 1.25, 95% confidence interval [CI] 1.19-1.31, P < .00001) and disease-free survival or recurrence-free survival (OR = 1.57, 95% CI 1.3-1.9, P < .00001) compared with observation; and the 4-year survival rate of patients who received postoperative adjuvant chemotherapy was better than the observation group (OR = 1.52, 95% CI 1.05-2.18, P = .03); and the 8-year survival rate of patients receiving postoperative adjuvant chemotherapy (OR = 1.5, 95% CI 0.94-2.4, P = .09) was comparable to the observation group., Conclusion: Receiving postoperative adjuvant chemotherapy improved people's survival and prolonged disease-free survival and recurrence-free survival in patients with stage IB non-small cell lung cancer compared with surgery alone., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors, and lung adenocarcinoma (LUAD) accounts for up to 40% of NSCLC. Ring finger protein 213(RNF213) has been demonstrated to suppress several cancers, including glioblastoma and breast cancer. Nonetheless, the role of RNF213 in LUAD has not been investigated. The expression of RNF213 in LUAD tissues was analyzed by western blotting, The Cancer Genome Atlas, Genotype Tissue Expression Project, and Gene Expression Omnibus databases. Prognostic value analysis was performed through the Kaplan-Meier Plotter database. We determined the role of RNF213 in LUAD cells through cell counting kit‑8 assay, migration, and invasion assay. The clinical roles of RNF213 were evaluated by immunohistochemical staining assay (IHC) and Kaplan-Meier survival analysis. RNF213 expression was reduced in LUAD, thus affecting the prognosis of LUAD. And RNF213 could suppress the migration and invasion of LUAD cells to prevent tumor development. the expression of RNF213 is positively correlated with the overall survival, providing a novel marker in the prognosis of LUAD patients.

Tumor-initiating cells (TICs) reprogram their metabolic features to meet their bioenergetic, biosynthetic, and redox demands. Our previous study established a role for wild-type isocitrate dehydrogenase 1 (IDH1 WT ) as a potential diagnostic and prognostic biomarker for non-small cell lung cancer (NSCLC), but how IDH1 WT modulates NSCLC progression remains elusive. Here, we report that IDH1 WT activates serine biosynthesis by enhancing the expression of phosphoglycerate dehydrogenase (PHGDH) and phosphoserine aminotransferase 1 (PSAT1), the first and second enzymes of de novo serine synthetic pathway. Augmented serine synthesis leads to GSH/ROS imbalance and supports pyrimidine biosynthesis, maintaining tumor initiation capacity and enhancing gemcitabine chemoresistance. Mechanistically, we identify that IDH1 WT interacts with and stabilizes PHGDH and fragile X-related protein-1 (FXR1) by impeding their association with the E3 ubiquitin ligase parkin by coimmunoprecipitation assay and proximity ligation assay. Subsequently, stabilized FXR1 supports PSAT1 mRNA stability and translation, as determined by actinomycin D chase experiment and in vitro translation assay. Disrupting IDH1 WT -PHGDH and IDH1 WT -FXR1 interactions synergistically reduces NSCLC stemness and sensitizes NSCLC cells to gemcitabine and serine/glycine-depleted diet therapy in lung cancer xenograft models. Collectively, our findings offer insights into the role of IDH1 WT in serine metabolism, highlighting IDH1 WT as a potential therapeutic target for eradicating TICs and overcoming gemcitabine chemoresistance in NSCLC.

Raman enhancement techniques are essential for gas analysis to increase the detection sensitivity of a Raman spectroscopy system. We have developed an efficient Raman enhancement technique called the collision-enhanced Raman scattering (CERS), where the active Raman gas as the analyte is mixed with a buffer gas inside the hollow-core photonic-crystal fiber (HCPCF) of a fiber-enhanced Raman spectroscopy (FERS) system. This results in an enhanced Raman signal from the analyte gas. In this study, we first showed that the intensity of the 587 cm -1 stimulated Raman scattering (SRS) peak of H 2 confined in an HCPCF is enhanced by as much as five orders of magnitude by mixing with a buffer gas such as helium or N 2 . Secondly, we showed that the magnitudes of Raman enhancement depend on the type of buffer gas, with helium being more efficient compared to N 2 . This makes helium a favorable buffer gas for CERS. Thirdly, we applied CERS for Raman measurements of propene, a metabolically interesting volatile organic compound (VOC) with an association to lung cancer. CERS resulted in a substantial enhancement of propene Raman peaks. In conclusion, the CERS we developed is a simple and efficient Raman-enhancing mechanism for improving gas analysis. It has great potential for application in breath analysis for lung cancer detection.

Purpose: To explore the impact of intrathecal pemetrexed (IP) on the survival of lung adenocarcinoma (LUAC) patients with leptomeningeal metastasis (LM)., Methods: We analyzed patients with LUAC and LM who received systemic therapy after LM diagnosis at the Fujian Cancer Hospital between July 2018 and March 2022. Patients who underwent IP were assigned to the IP group; those without IP treatment were designated as the non-IP group. Propensity score matching (PSM) was performed between the two groups., Results: 165 patients were enrolled: 83 and 82 in the IP and non-IP groups, respectively. After 1:1 PSM, we included 114 patients in the matched cohort. Median overall survival (OS) was 13.2 months (95% CI 10.8-15.6 months) in the IP group versus 10.1 months (95% CI 5.3-14.9 months) in the non-IP group (P = 0.488). Only Eastern Cooperative Oncology Group Performance Status (ECOG PS) was confirmed as an independent predictor for OS in the matched cohort (hazard ratio (HR) 2.03; P = 0.023). Multivariate competing-risks analysis showed that IP significantly correlated with central nervous system-related death (HR 0.31; P = 0.046). When stratified by ECOG PS, IP improved survival in patients with poor ECOG PS (PS = 2) (14.3 months vs. 1.6 months; P = 0.003)., Conclusions: Intrathecal pemetrexed did not enhance OS for the entire LUAC patient with LM compared to non-intrathecal chemotherapy. However, it exhibited the potential to reduce the risk of central nervous system-related mortality and improve survival in patients with poor ECOG PS., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: This study aimed to establish a nomogram for predicting risk of recurrence and provide a model for decision-making between lobectomy and sublobar resection in patients with stage IA lung adenocarcinoma., Methods: Patients diagnosed with stage IA lung adenocarcinoma (LUAD) between December 2010 and October 2018 from Cancer Hospital Chinese Academy of Medical Sciences were included. Patients were randomly assigned to training and validation cohorts, accounting for 70% and 30% of the total cases, respectively. We collected laboratory variables before surgery. Univariate and multivariate analyses were performed in the training cohort to identify variables significantly associated with recurrence-free survival (RFS) which were subsequently used to construct a nomogram. Validation was conducted in both cohorts. A receiver operating characteristic curve was used to determine the optional cutoff values of the scores calculated from the nomogram. Patients were then divided into low- and high-risk groups. Survival was performed to determine if the nomogram could guide the operation method., Results: A total of 543 patients were included in this study. Gender, albumin level, carcinoembryonic antigen level and cytokeratin-19-fragment level were included in the nomogram. In both cohorts, the nomogram stratified the patients into high- and low-risk groups in terms of RFS. In particular, there was a significant difference in RFS between lobectomy and sublobar resection in the high-risk group., Conclusions: Gender, albumin level, carcinoembryonic antigen level and cytokeratin-19-fragment level are valuable markers in predicting recurrence and can guide surgical practice in patients with stage IA LUAD., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: Patients with malignant pleural effusion (MPE) typically have poor prognoses, and predicting survival is challenging. The present study aimed to identify prognostic factors of overall survival (OS) in non-small cell lung cancer (NSCLC) patients with MPE in the time of immunotherapy and targeted therapy., Methods: Data of 344 consecutive NSCLC patients with MPE on clinical, radiological, and molecular characteristics and treatment options were collected. The risk factors in the training cohort were assessed using univariate and multivariate proportional hazards analyses. A clinical prognostic score was established and validated., Results: According to the results of the multivariable survival analysis, the Eastern Cooperative Oncology Group (ECOG) performance score (PS), antiangiogenic therapy, immunotherapy, and lactic dehydrogenase (LDH) in pleural fluid (CAIL) prognostic score was developed (n = 275) and subsequently validated (n = 69). Patients who underwent risk stratification into low-, moderate-, and high-risk groups had median OS of 46.1, 23.1, and 9.6 months, respectively (P < 0.0001). The area under the curve (AUC) analysis showed the CAIL score to be superior at predicting survival compared with the LENT score at 6 (0.84 vs. 0.77, P < 0.01), 12 (0.87 vs. 0.82, P < 0.01), and 36 months (0.80 vs. 0.77, P < 0.01)., Conclusions: For NSCLC patients with MPE, the validated CAIL prognostic score integrates clinical characteristics and therapeutic modalities to predict survival., (© 2023 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd.)

Background: Despite the growing interest in the impact of the gut microbiome on cancer, the relationship between the lung microbiome and lung cancer has received limited investigation. Additionally, the composition of the oral microbiome was found to differ from that of individuals with lung cancer, indicating that these microorganisms may serve as potential biomarkers for the detection of lung cancer., Methods: Forty-three Chinese lung cancer patients were enrolled in the current retrospective study and 16 S rRNA sequencing was performed on saliva, cancerous tissue (CT) and paracancerous tissue (PT) samples., Results: Diversity and species richness were significantly different between the oral and lung microbiota. Lung microbiota were largely composed of the phyla Proteobacteria, Firmicutes, Bacteroidetes and Actinobacteria. The relative abundance of Promicromonosporacea and Chloroflexi increased in CT, while Enterococcaceae and Enterococcus were enriched in PT (p<0.05). A cancer-related microbiota model was constructed and produced an area under the curve of 0.74 in the training set, indicating discrimination between subjects with and without cancer., Conclusions: Characterization of microbiota in saliva, CT and PT from Chinese lung cancer patients revealed little difference between CT and PT, indicating that the tumor and its microenvironment might influence the local microbiome. A model to distinguish between CT and PT was constructed, which has the potential to enhance our comprehension of the involvement of microbiota in the pathogenesis of lung cancer and identify novel therapeutic targets., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: To investigate the diagnostic value of loop-mediated thermostatic amplification (LAMP) in detecting pathogenic bacteria from bronchoalveolar lavage fluid (BALF) of patients with pulmonary disorders combined with lower respiratory tract infections (LRTI)., Methodology: This cross-sectional study included patients with pulmonary disorders combined with LRTI, including chronic obstructive pulmonary disease (COPD), bronchiectasis, or lung cancer, hospitalized in Meizhou People's Hospital between January 2020 and October 2021. BALF was collected using local bronchoalveolar lavage and electronic bronchoscopy. The presence of the pathogens was confirmed using the LAMP method and the bacterial culture method., Results: In total, 249 patients were included (135 with COPD, 73 with bronchiectasis, and 41 with lung cancer). The proportions of Methicillin-resistant Staphylococcus aureus (4.8% vs 0.4%, p = 0.02) and Haemophilus influenzae (6.8% vs 0.4%, p < 0.001) detected by the LAMP method was higher, while the proportion of Pseudomonas aeruginosa was lower compared with that of the culture method (6.8% vs 12.4%, p = 0.034). The bacterial species with the highest agreement coefficient was Stenotrophomonas maltophilia (Kappa = 0.798, p < 0.001). Furthermore, 9 COPD patients exhibited mixed infections as determined by the LAMP method, whereas the culture method detected only 2 of these cases (1.48%) (p < 0.05)., Conclusions: LAMP can detect more pathogenic bacteria, notably Haemophilus influenza, Methicillin-resistant Staphylococcus aureus, and atypical pathogens in patients with clinically common pulmonary disorders combined with LRTI. LAMP may provide etiological evidence to guide the clinical use of antibiotics in primary hospitals., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2023 Ya Wen, Juan Huang, Yanjia Du, Zishuang Zhong, Hanhua Zeng, Weiqiang Zhang.)

High tumour programmed cell death-ligand 1 (PD-L1) expression is associated with poor progression-free survival (PFS) after tyrosine kinase inhibitor (TKI) therapy in ALK -rearranged non-small cell lung cancer (NSCLC). However, the characteristics of the tumour microenvironment (TME) and their prognostic values in ALK -rearranged NSCLC are unknown. Here, we collected tumour tissues from pretreated ALK -rearranged NSCLC patients, immunohistochemical staining was used to assess PD-L1 expression, and tumour-infiltrating immune cells were determined via multiplex immunofluorescence staining (mIF). Our data showed that the median values of PFS for the high PD-L1 group and low PD-L1 group who received ALK-TKI treatment were 4.4 and 16.4 months, respectively ( p = 0.008). The median overall survival (OS) of the two groups was 24.0 months and not reached, respectively ( p = 0.021). Via univariate and multivariate analyses, a high PD-L1 expression and a worse ECOG PS were determined to be independent prognostic factors of OS (HR = 3.35, 95% CI: 1.23-9.11, p = 0.018; HR = 6.42, 95% CI: 1.45-28.44, p = 0.014, respectively). In addition, the high PD-L1 group had increased Tregs and exhausted CD8+ T cells in both the tumour and stroma (all p < 0.05). High PD-L1 expression was an adverse predictive and prognostic biomarker for ALK -rearranged NSCLC. The characteristics of the TME in patients with high PD-L1 expression were shown to have an immunosuppressive status.

Aim: To identify risk factors for self-reported cognitive impairment in radically treated stage III non-small cell lung cancer (NSCLC)., Methods: Cognitive functioning was assessed using the EORTC-QLQ-C30 at seven pre-specified time points in the phase III NVALT-11 trial (observation versus prophylactic cranial irradiation [PCI] in stage III NSCLC treated with chemo-radiotherapy ± surgery). Cognition was analyzed as binary (impairment or not) and continuous outcome, respectively, using generalized estimating equation (GEE) before and after multiple imputation. A score < 75 was defined as cognitive impairment. A mean difference by < 10, 10-<20, ≥ 20 points was regarded as of no, moderate, and large clinical effect, respectively. We categorized the cognitive impairment into four types based on changes over time: sustained, reversible, recurring, and alternating., Results: In the no-PCI arm, 43/84 [51.2%] reported cognitive impairment at least once, of which 31.4% were sustained, 25.7% reversible, 28.6% recurring, and 14.3% alternating. Results were similar in the PCI arm. Cognitive functioning at baseline was comparable in two arms and a score < 75 was a significant risk factor with large effect for subsequent cognitive impairment (no-PCI: β = -23.30, p < 0.001; PCI arm: β = -22.34, p < 0.001; All: β = -23.47, p < 0.001). Younger age (≤60y), squamous histology, and PCI were risk factors without clinical relevance (β > -10, p < 0.05). Cognitive functioning declined over time (β = -0.26, p = 0.001) except for patients with cognitive impairment at baseline (β = 0.141, p = 0.33)., Conclusion: Cognitive impairment is dynamic over time with four types. Baseline cognitive impairment (score < 75) is the most important risk factor for subsequent cognitive impairment in stage III NSCLC. Note: This work has been partly reported as an oral presentation at the ESTRO 2021 meeting (OC-0176)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Pulmonary epithelioid hemangioendothelioma (PEH) is a rare vascular tumor with no established treatment protocol. The authors report the case of a young woman diagnosed with PEH. DNA and RNA analysis by next-generation sequencing was performed on the tumor tissue. A novel germline PALB2 mutation and classical  WWTR1-CAMTA1 fusion were identified. She experienced a poor response to sintilimab (a PD-1 inhibitor) plus platinum-based chemotherapy as the first-line treatment. PEH patients harboring a germline PALB2 mutation and WWTR1-CAMTA1 gene fusion may respond poorly to treatment with PD-1 inhibitors plus chemotherapy.

Immunotherapy has significantly improved clinical outcomes of non-small cell lung cancer (NSCLC), however, along with the popularization of immunotherapy, immune resistance has become an unavoidable problem. Immunotherapy can induce extensive cellular and molecular alterations in the tumor microenvironment. Considering the mechanisms of immune resistance are not yet fully understood and the efficacy of standard chemotherapy regimens is limited, more effective coping strategies based on resistance mechanisms are urgently needed. In this review, we intend to summarize the known mechanisms of immune resistance and feasible strategies, so as to provide a foundation for clinicians to develop more individualized and precise regimens and finally improve patients' prognosis.
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We reported the manifestations, auxiliary examination, and treatment courses of a case of scimitar syndrome with pulmonary sequestration containing carcinoma. The clinical characteristics of scimitar syndrome with pulmonary sequestration, pulmonary sequestration containing carcinoma were summarized based on the data of this case and the related literatures before January 2022. Scimitar syndrome can coexist with ipsilateral pulmonary sequestration. Because sequestered lung tissue has a risk of malignant transformation, a cancer screening test is useful for early diagnosis and timely treatment.

Small cell lung cancer (SCLC) is the most devastating subtype of lung cancer with no clinically available prognostic biomarkers. N 6 -methyladenosine (m 6 A) and noncoding RNAs play critical roles in cancer development and treatment response. However, little is known about m 6 A-related long noncoding RNAs (lncRNAs) in SCLC. We used 206 limited-stage SCLC (LS-SCLC) samples from two cohorts to undertake the first and most comprehensive exploration of the m 6 A-related lncRNA profile in SCLC and constructed a relevant prognostic signature. In total, 289 m 6 A-related lncRNAs were screened out. We then built a seven-lncRNA-based signature in the training cohort with 48 RNA sequencing data using univariate and multivariate Cox regression models. The signature was well validated in an independent cohort containing 158 cases with quantitative PCR data. In both cohorts, the signature divided patients into high- and low-risk groups with significantly different survival rates (both p < 0.001). Our signature predicted chemotherapy survival benefit in patients with LS-SCLC. Receiver operating characteristic and C-index analyses indicated that the signature was better at predicting prognosis and chemotherapy benefit than other clinicopathologic features. Moreover, the signature was identified as an independent predictor of prognosis and chemotherapy response in different cohorts. Furthermore, functional analysis showed that multiple activated immune-related pathways were enriched in the low-risk group. Additionally, the signature was also closely related to various immune checkpoints and inflammatory responses. We generated the first clinically available m 6 A-related lncRNA signature to predict prognosis and chemotherapy benefit in patients with LS-SCLC. Our findings could help optimize the clinical management of patients with LS-SCLC and inform future therapeutic targets for SCLC., (© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Objectives: To investigate the outcome difference of whole brain radiotherapy (WBRT) and involved-field radiotherapy (IFRT) in limited-stage small-cell lung cancer (LS-SCLC) patients with recurrent brain metastases (BMs) after prophylactic cranial irradiation (PCI)., Methods: A retrospective analysis was carried out in 68 LS-SCLC patients who underwent WBRT or IFRT owing to the occurrence of recurrent BMs after PCI from 2009 to 2020., Results: The median overall survival (OS) of all patients was 11.43 months [95% confidence interval (CI) 9.39-13.48 months]. In the paired comparison of OS, the IFRT group had a significantly longer survival time than the WBRT group in all patients [17.80 months vs. 8.47 months; hazard ratio (HR), 0.393, 95% CI, 0.213-0.728; P = 0.002] and 46 matched patients (18.23 months vs. 8.73 months; HR, 0.411, 95% CI, 0.195-0.865; P = 0.019). In terms of the intra-cranial progression-free survival (iPFS), there was no significant difference between the WBRT group and IFRT group before matching (5.93 months vs. 7.30 months; HR, 0.644, 95% CI, 0.373-1.112; P = 0.111); similarly, no statistical difference was detected between the WBRT group and IFRT group after matching (5.33 months vs. 8.10 months; HR, 0.623, 95% CI, 0.323-1.199; P = 0.152). Meanwhile, of the 41 patients with symptoms, 27 cases (65.9%) had symptom relief, showing tolerable toxicity without unexpected toxicity during the observation., Conclusions: Compared with WBRT, IFRT exhibits better survival benefits for LS-SCLC patients with recurrent BMs after PCI. Re-irradiation for BMs exhibits advantages of symptom relief and tolerable side effects., Competing Interests: None

Evidences propound tumor growth may be impeded by blocking angiogenesis. Before we showed that sulfated glucan or arabinogalactan might bind to BMP2 or its receptors to inhibit angiogenesis. Whether sulfated galactoglucan can target both BMPRIA and BMPRII to impede angiogenesis and tumor cells growth is still vague. Here, we prepare galactoglucan and its sulfated derivatives Sul-CDA-0.05. The sulfate groups substituted are at the C-6 of 1, 4-linked α-Glcp and 1, 4-linked α-Galp backbone and at the C-6 of branch chain T-linked α-Glcp. Sul-CDA-0.05 can inhibit angiogenesis in vitro and in vivo. Indeed, Sul-CDA-0.05 impedes xenografted A549 lung tumor cells growth. Mechanism study demonstrates that this polysaccharide may target both BMPRIA and BMPRII to block BMP/Smad/Id1 signaling and attenuate VEGF and its transcription factor. Our evidences suggest that Sul-CDA-0.05 may be a new drug candidate for anti-lung cancer therapy by targeting both BMPRIA and BMPRII., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: To investigate the effect of spread through air spaces (STAS) on the postoperative prognosis of patients with stage pT1N0M0 lung adenocarcinoma according to different tumor sizes. Methods: The clinicopathological and follow-up data of 511 patients with pT1N0M0 lung adenocarcinoma treated surgically in the Department of Thoracic Surgery, Cancer Hospital, Chinese Academy of Medical Sciences from January 2014 to June 2018 were retrospectively analyzed. There were 285 males and 226 females, aged 60 (53, 66) years. Those patients were divided into two groups according to STAS status, including STAS (-) group (342 cases) and STAS (+) group (169 cases). And the stratified analysis was performed according to the American Cancer Consortium (AJCC) 8th edition postoperative pathological tumor size T-stage (pT) of lung cancer, which was divided into pT1a (pT≤1 cm, 93 cases), pT1b (1 cm0.05]. Before and after IPTW adjustment, statistically significant differences were found in RFS between STAS (+) group and STAS (-) group [(72.50±2.23) vs (85.12±0.72) months, (77.74±1.12) vs (84.59±0.64) months, all P <0.001]. In addition, the risks of both local and distant recurrence were higher in STAS (+) group compared to STAS (-) group (6.7% vs 1.2% and 8.2% vs 3.6%, respectively; both P< 0.05). Conclusion: For lung adenocarcinoma patients with pT1bN0M0 and pT1cN0M0, those patients with STAS (+) had a higher incidence of both local and distant recurrence and with poor RFS.

Background: Early diagnosis of lung cancer is a key intervention for the treatment of lung cancer in which computer-aided diagnosis (CAD) can play a crucial role. Most published CAD methods perform lung cancer diagnosis by classifying each lung nodule in isolation. However, this does not reflect clinical practice, where clinicians diagnose a patient based on a set of images of nodules, instead of looking at one nodule at a time. Besides, the low interpretability of the output provided by these methods presents an important barrier for their adoption., Method: In this article, we treat lung cancer diagnosis as a multiple instance learning (MIL) problem, which better reflects the diagnosis process in the clinical setting and provides higher interpretability of the output. We selected radiomics as the source of input features and deep attention-based MIL as the classification algorithm. The attention mechanism provides higher interpretability by estimating the importance of each instance in the set for the final diagnosis. To improve the model's performance in a small imbalanced dataset, we propose a new bag simulation method for MIL., Results and Conclusion: The results show that our method can achieve a mean accuracy of 0.807 with a standard error of the mean (SEM) of 0.069, a recall of 0.870 (SEM 0.061), a positive predictive value of 0.928 (SEM 0.078), a negative predictive value of 0.591 $0.591$ (SEM 0.155), and an area under the curve (AUC) of 0.842 (SEM 0.074), outperforming other MIL methods. Additional experiments show that the proposed oversampling strategy significantly improves the model's performance. In addition, experiments show that our method provides a good indication of the importance of each nodule in determining the diagnosis, which combined with the well-defined radiomic features, to make the results more interpretable and acceptable for doctors and patients., (© 2022 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

The cellular origin of hepatocellular carcinomas (HCC) and the role of Notch1 signalling in HCC initiation are controversial. Herein, we establish Notch1 as a regulator of HCC development and progression. Clinically, high Notch1 expression correlates with enhanced cancer progression, elevated lung metastasis, increased cancer stem cell (CSC)-like cells' gene signature expression, and poor overall survival in HCC patients. Notch1 intracellular domain (N1ICD) overexpression spontaneously transforms rat liver progenitor cells (LPC) into CSC-like cells (WB N1ICD C5) under a selective growth environment, while orthotopic injection of these cells generates liver tumors and spontaneous pulmonary metastasis in an isogenic rat model. Mechanistically, the elevated Notch1 activity increases c-myc expression, which then transcriptionally upregulates VCAM1 expression to activate macrophage dependent HCC transendothelial migration. In vivo, silencing c-myc prohibits the tumorigenicity of WB N1ICD C5 cells, while depletion of VCAM1 reduces spontaneous lung metastasis without affecting primary WB N1ICD C5 orthotopic liver tumor growth. Importantly, depletion of macrophage or blockade of macrophage VCAM1 binding receptor α4β1-integrin reduces the number of WB N1ICD C5 lung nodules in an experimental metastasis model. Overall, our work discovers that the Notch1-c-myc-VCAM1 signaling axis initiates LPC-driven hepatocarcinogenesis and metastasis, providing a preclinical model for HCC study and therapeutic targets for an improved HCC treatment., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: To investigate the value of endobronchial ultrasound (EBUS) and virtual bronchoscopic navigation (VBN) combined with rapid on-site evaluation (ROSE) in diagnosing peripheral pulmonary lesions (PPLs)., Methods: Between January 1st 2019 to September 1st 2021, EBUS and VBN examination were performed in expected consecutive patients with PPLs who were admitted to Zhangzhou Affiliated Hospital of Fujian Medical University (Fujian, China). Finally, based on the calculation of expected diagnostic yield of R-EBUS biopsy and drop out, 198 eligible patients were randomly divided into ROSE group (100 cases) and non-ROSE group (98 cases). The diagnostic yield of brushing and biopsy, the complications, the procedure time, the diagnosis time and expense during diagnosis were analyzed., Results: In the ROSE group, the positive rate of EBUS brushing and biopsy were 68%, 84%, respectively. The average procedure time and diagnosis time were 18.6 ± 6.8 min, 3.84 ± 4.28 days, respectively, and the average expense was 643.44 ± 706.56 US.$ (4093.15 ± 4494.67 yuan ¥). In the controls, the positive rate of brushing and biopsy were 44%, 74%, respectively. The average procedure time and diagnosis time were 15.4 ± 5.7 min, 6.46 ± 3.66 days, respectively. And the average expense during diagnosis was 1009.27 ± 713.89 US.$ (6420.28 ± 4541.33 yuan ¥). There was significant difference in the positive rate of EBUS brushing and biopsy, diagnosis time and expense during diagnosis between both groups. And no significant difference was observed in the complications and the procedure time. Additionally, the impact of ROSE on diagnostic yield in right upper lobe and the size of lesion ≤ 2 cm in diameter was significant., Conclusion: In combination with ROSE, EBUS could significantly improve the positive rate of diagnosing PPLs, shorten diagnosis time and reduce expense during diagnosis. ROSE will be of great importance in the diagnosis of PPLs and medical resource., (© 2022. The Author(s).)

Background: The early-stage lung adenocarcinoma (LUAD) incidence has increased with heightened public awareness and lung cancer screening implementation. Lipid metabolism abnormalities are associated with lung cancer initiation and progression. However, the comprehensive features and clinical significance of the immunometabolism landscape and lipid metabolism-related genes (LMRGs) in cancer recurrence for early-stage LUAD remain obscure., Methods: LMRGs were extracted from Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Samples from The Cancer Genome Atlas (TCGA) were used as training cohort, and samples from four Gene Expression Omnibus (GEO) datasets were used as validation cohorts. The LUAD recurrence-associated LMRG molecular pattern and signature was constructed through unsupervised consensus clustering, time-dependent receiver operating characteristic (ROC), and least absolute shrinkage and selection operator (LASSO) analyses. Kaplan-Meier, ROC, and multivariate Cox regression analyses and prognostic meta-analysis were used to test the suitability and stability of the signature. We used Gene Ontology (GO), KEGG pathway, immune cell infiltration, chemotherapy response analyses, gene set variation analysis (GSVA), and GSEA to explore molecular mechanisms and immune landscapes related to the signature and the potential of the signature to predict immunotherapy or chemotherapy response., Results: First, two LMRG molecular patterns were established, which showed diverse prognoses and immune infiltration statuses. Then, a 12-gene signature was identified, and a risk model was built. The signature remained an independent prognostic parameter in multivariate Cox regression and prognostic meta-analysis. In addition, this signature stratified patients into high- and low-risk groups with significantly different recurrence rates and was well validated in different clinical subgroups and several independent validation cohorts. The results of GO and KEGG analyses and GSEA showed that there were differences in multiple lipid metabolism, immune response, and drug metabolism pathways between the high- and low-risk groups. Further analyses revealed that the signature-based risk model was related to distinct immune cell proportions, immune checkpoint parameters, and immunotherapy and chemotherapy response, consistent with the GO, KEGG, and GSEA results., Conclusions: This is the first lipid metabolism-based signature for predicting recurrence, and it could provide vital guidance to achieve optimized antitumor for immunotherapy or chemotherapy for early-stage LUAD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhu, Zeng, Fan, Lei, Wang, Zheng, Wang, Zeng, Tan, Sun, Xue and He.)

Background: To date, immunotherapy has improved the 5-year survival rate of patients with advanced non-small cell lung cancer (NSCLC) from 4% to 15%. However, only 30%-50% of the NSCLC patients respond to immune checkpoint inhibitors (ICIs) immunotherapy. Therefore, screening patients for potential benefit with precise biomarkers may be of great value., Methods: First, an immunotherapy NSCLC cohort was analyzed to identify the gene mutations associated with the prognosis of ICI treatment. Further analyses were conducted using NSCLC cohort in The Cancer Genome Atlas (TCGA) project to validate the correlations between the specific gene mutations and tumor immunogenicity, antitumor immunity, and alterations in the tumor-related pathways using Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) and Gene set enrichment analysis (GSEA)., Results: In the immunotherapy NSCLC cohort (n = 266), significantly longer overall survival (OS) rates were observed in the PAK7 -mutant type (PAK7-MT) group (n = 13) than the PAK7 -wild type (PAK7-WT) group (n = 253) ( P = 0.049, HR = 0.43, 95%CI = 0.23-0.79). In the TCGA cohort, PAK7 mutations were correlated with the higher tumor mutation burden (TMB) (14.18 vs. 7.13, P < 0.001), increased neoantigen load (NAL) (7.52 vs. 4.30, P < 0.001), lower copy number variation (CNV), and higher mutation rate in the DNA damage response (DDR)-related pathways. In addition, PAK7 mutations were also positively correlated with immune-related genes expressions and infiltrating CD8+ T cells (0.079 vs. 0.054, P = 0.005). GSEA results showed that several tumor-related pathways varied in the PAK7-MT group, suggesting the potential mechanisms that regulate the tumor immune-microenvironment., Conclusions: This study suggested that the PAK7 mutations might be a potential biomarker to predict the efficacy of immunotherapy for NSCLC patients. Considering the heterogeneity among the patients and other confounding factors, a prospective clinical trial is proposed to further validate the impact of PAK7 mutation on the immunotherapy outcomes in NSCLC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zeng, Tong, Bin, Peng, Gao, Xia, Yi and Dong.)

Adenosine-to-inosine (A-to-I) RNA editing is a widespread posttranscriptional modification that has been shown to play an important role in tumorigenesis. Here, we evaluated a total of 19,316 RNA editing sites in the tissues of 80 lung adenocarcinoma (LUAD) patients from our Nanjing Lung Cancer Cohort (NJLCC) and 486 LUAD patients from the TCGA database. The global RNA editing level was significantly increased in tumor tissues and was highly heterogeneous across patients. The high RNA editing level in tumors was attributed to both RNA (ADAR1 expression) and DNA alterations (mutation load). Consensus clustering on RNA editing sites revealed a new molecular subtype (EC3) that was associated with the poorest prognosis of LUAD patients. Importantly, the new classification was independent of classic molecular subtypes based on gene expression or DNA methylation. We further proposed a simplified model including eight RNA editing sites to accurately distinguish the EC3 subtype in our patients. The model was further validated in the TCGA dataset and had an area under the curve (AUC) of the receiver operating characteristic curve of 0.93 (95%CI: 0.91-0.95). In addition, we found that LUAD cell lines with the EC3 subtype were sensitive to four chemotherapy drugs. These findings highlighted the importance of RNA editing events in the tumorigenesis of LUAD and provided insight into the application of RNA editing in the molecular subtyping and clinical treatment of cancer., (© 2021. Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. Although dysbiosis of the lung and gut microbiota have been associated with NSCLC, their relative contributions are unclear; in addition, their roles in distant metastasis (DM) are still illusive. We recruited in total 121 participants, including 87 newly diagnosed treatment-naive NSCLC patients of various stages and 34 healthy volunteers, and surveyed their fecal and sputum microbiota. We compared the microbial profiles between groups, identified microbial biomarkers, and generated machine learning models for distinguishing healthy individuals from patients with NSCLC and patients of various stages. We found significant perturbations of gut and sputum microbiota in patients with NSCLC and DM. A machine learning model combining both microbiota (combined model) performed better than an individual data set in patient stratification, with the highest area under the curve (AUC) value of 0.896. Sputum and gut microbiota both contributed to the combined model; in most cases, sputum-only models performed similar to the combined models. Several microbial biomarkers were shared by both microbiotas, indicating their similar roles at distinct body sites. Microbial biomarkers of distinct disease stages were mostly shared, suggesting biomarkers for DM could be acquired early. Furthermore, Pseudomonas aeruginosa, a species previously associated with wound infections, was significantly more abundant in brain metastasis, indicating that distinct types of DMs could have different microbes. Our results indicate that alterations of the sputum microbiota have stronger relationships with NSCLC and DM than the gut and strongly support the feasibility of metagenome-based noninvasive disease diagnosis and risk evaluation. (This study has been registered at ClinicalTrials.gov under registration no. NCT03454685). IMPORTANCE Our survey on gut and sputum microbiota revealed that both were significantly disturbed in non-small cell lung cancer (NSCLC) and associated with distant metastasis (DM) while only the sputum microbiota was associated with non-DM NSCLC. The lung microbiota could therefore have a stronger association with (and thus may contribute more to) disease development than the gut microbiota. Mathematic models using both microbiotas performed better in patient stratification than using individual microbiota. Sputum models, however, performed similar to the combined models, suggesting a convenient, noninvasive diagnostic for NSCLC. Microbial biomarkers of distinct disease stages were mostly shared, suggesting that the same set of microbes were underlying disease progression, and the signals for distant metastasis could be acquired at early stages of the disease. Our results strongly support the feasibility of noninvasive diagnosis of NSCLC, including distant metastasis, are of clinical importance, and should warrant further research on the underlying molecular mechanisms.

Telomere is a specialized DNA-protein complex that plays an important role in maintaining chromosomal integrity. Shelterin is a protein complex formed by six different proteins, with telomeric repeat factors 1 (TRF1) and 2 (TRF2) binding to double-strand telomeric DNA. Telomeric DNA consists of complementary G-rich and C-rich repeats, which could form G-quadruplex and intercalated motif (i-motif), respectively, during cell cycle. Its G-rich transcription product, telomeric repeat-containing RNA (TERRA), is essential for telomere stability and heterochromatin formation. After extensive screening, we found that acridine derivative 2c and acridine dimer DI26 could selectively interact with TRF1 and telomeric i-motif, respectively. Compound 2c blocked the binding of TRF1 with telomeric duplex DNA, resulting in up-regulation of TERRA. Accumulated TERRA could bind with TRF1 at its allosteric site and further destabilize its binding with telomeric DNA. In contrast, DI26 could destabilize telomeric i-motif, resulting in down-regulation of TERRA. Both compounds exhibited anti-tumour activity for A549 cells, but induced different DNA damage pathways. Compound 2c significantly suppressed tumour growth in A549 xenograft mouse model. The function of telomeric i-motif structure was first studied with a selective binding ligand, which could play an important role in regulating TERRA transcription. Our results showed that appropriate level of TERRA transcript could be important for stability of telomere, and acridine derivatives could be further developed as anti-cancer agents targeting telomere. This research increased understanding for biological roles of telomeric i-motif, TRF1 and TERRA, as potential anti-cancer drug targets.

Background: Stage information is crucial for cancer care and essential to improve polices for cancer control. However, the distribution of stage at diagnosis for common cancers in China is not well known. We aimed to identify the distribution and factors associated with stage at diagnosis for five major cancers in China., Methods: In this multicentre, hospital-based, observational study, we included 23 hospitals in 12 provinces from China. We focused on cancers of the lung, stomach, oesophagus, colorectum, and female breast, and using electronic medical records at the individual level from the local hospitals, and cancer registration records from population-based cancer registries, identified diagnoses made between Jan 1, 2016, and Dec 31, 2017. We collected information on sociodemographic characteristics, lifestyle factors, insurance types, and stage at diagnosis. We analysed the prevalence of late-stage (stages III-IV) cancer cases overall, by sex, and by geographical region. We used logistic regression to identify the factors that were associated with late stage at diagnosis. We further compared these estimates with data from the USA using the Surveillance, Epidemiology, and End Results database., Findings: We included 52 103 eligible patients. Among 41 671 patients with known stage at diagnosis, 22 009 (52·8%) were diagnosed with late-stage cancer. The proportion of late-stage cases was higher in men and boys than in women and girls (14 084 [64·1%] of 21 973 vs 7925 [40·2%] of 19 698 patients; diagnosed at stages III-IV; adjusted odds ratio [OR] 1·3, 95% CI 1·2-1·5). There is a persistent diagnostic disparity between rural and urban areas (adjusted OR 1·2, 1·1-1·4). Patients with the new rural cooperative medical scheme insurance had a significantly higher risk of late-stage diagnosis compared with patients with urban insurance (adjusted OR 1·4, 1·1-1·9). By specific cancer type, sex and rural-urban disparities were the largest in lung cancer. Compared with the USA, our study patients had a higher percentage of stage II-IV breast cancer (72·4% in China vs 48·8% in the USA), lung cancer (82·7% in China vs 74·7% in the USA), and colorectal cancer (84·8% in China vs 75·9% in the USA)., Interpretation: The disparities of cancer diagnosis within China, and between China and the USA, indicate an urgent need for early detection of cancer in China., Funding: National Key R&D Programme of China, Major State Basic Innovation Programme of the Chinese Academy of Medical Sciences, and National Natural Science Fund., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Small cell lung cancer (SCLC) is lethal and possesses limited therapeutic options. Platinum-based chemotherapy-with or without immune checkpoint inhibitors (anti-PDs)-is the current first-line therapy for SCLCs; however, its associated outcomes are heterogeneous. N 6 -methyladenosine (m 6 A) is a novel and decisive factor in tumour progression, chemotherapy resistance, and immunotherapy response. However, m 6 A modification in SCLC remains poorly understood., Methods: We systematically explored the molecular features and clinical significance of m 6 A regulators in SCLC. We then constructed an m 6 A regulator-based prognostic signature (m 6 A score) based on our examination of 256 cases with limited-stage SCLC (LS-SCLC) from three different cohorts-including an independent cohort that contained 150 cases with qPCR data. We additionally evaluated the relationships between the m 6 A score and adjuvant chemotherapy (ACT) benefits and the patients' responses to anti-PD-1 treatment. Immunohistochemical (IHC) staining and the HALO digital pathological platform were used to calculate CD8+ T cell density., Results: We observed abnormal somatic mutations and expressions of m 6 A regulators. Using the LASSO Cox model, a five-regulator-based (G3BP1, METTL5, ALKBH5, IGF2BP3, and RBM15B) m 6 A score was generated from the significant regulators to classify patients into high- and low-score groups. In the training cohort, patients with high scores had shorter overall survival (HR, 5.19; 2.75-9.77; P < 0.001). The prognostic accuracy of the m 6 A score was well validated in two independent cohorts (HR 4.6, P = 0.006 and HR 3.07, P < 0.001). Time-dependent ROC and C-index analyses found the m 6 A score to possess superior predictive power than other clinicopathological parameters. A multicentre multivariate analysis revealed the m 6 A score to be an independent prognostic indicator. Additionally, patients with low scores received a greater survival benefit from ACT, exhibited more CD8+ T cell infiltration, and were more responsive to cancer immunotherapy., Conclusions: Our results, for the first time, affirm the significance of m 6 A regulators in LS-SCLC. Our multicentre analysis found that the m 6 A score was a reliable prognostic tool for guiding chemotherapy and immunotherapy selections for patients with SCLC., (© 2021. The Author(s).)

Background: The genomic mutation and immune feature landscape of ERBB2 exon 20 insertion (ERBB2-ex20ins)-driven non-small cell lung cancer and the features associated with the response to chemoimmunotherapy are currently unknown., Methods: The genomic landscape of ERBB2-ex20ins lung adenocarcinoma (LUAD) patients was characterized by next-generation sequencing (NGS) of 1021 cancer genes. The clinical outcomes of chemoimmunotherapy were evaluated among 13 patients with stage IV ERBB2-ex20ins LUAD, and potential biomarkers of the response to chemoimmunotherapy were explored using NGS and T cell receptor sequencing., Results: Among 8247 LUAD patients, 207 (2.5%) had ERBB2-ex20ins, of whom 181 (87.4%) harbored more than one comutation. The most common comutations were in TP53. Patients with ERBB2-ex20ins had a low tumor mutational burden (TMB; median, 4.2 mutations/Mb), and most (66.7%) were PD-L1 negative. Thirteen of the 207 patients received chemoimmunotherapy, for whom the objective response rate, disease control rate, and median progression-free survival were 31%, 77%, and 8.0 months, respectively. Responders exhibited a higher TMB and a trend toward lower clonality in tumors compared with nonresponders (p = 0.0067 and p = 0.085, respectively). A high TMB combined with mutations in DNA damage repair pathways and SWI/SNF chromatin remodeling complexes was associated with a benefit from chemoimmunotherapy., Conclusions: The efficacy and outcome of chemoimmunotherapy were encouraging among ERBB2-ex20ins LUAD patients, who were characterized by low TMB and negative PD-L1 expression. The combination of TMB and comutations is a potential biomarker to identify patients who will benefit from chemoimmunotherapy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Lung cancer is the malignancy with the highest mortality rate worldwide. Malignant pleural effusion (MPE) caused by advanced lung cancer severely affects the quality of life and prognosis of patients. Tumor-associated genetic testing is the basis for making precise treatment decisions. There are some risks of tissue biopsy, and it is difficult to sample repeatedly. Due to its non-invasive and can reflect the full profile of tumor gene characteristics, liquid biopsy is increasingly used in the diagnosis and treatment of lung cancer. Because of the extremely low DNA level of circulating tumor, the sensitivity and specificity of liquid biopsy based on blood samples are limited. Tumor cells is enriched in MPE. The detection of cell-free DNA, extracellular vesicles and microRNA in MPE will be helpful to the diagnose, treatment and assess prognosis of patients with lung cancer. This review aims to discuss the research progress of liquid biopsy based on MPE in the diagnosis and treatment of lung cancer patients.
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