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Lung cancer is the top reason for cancer-related deaths worldwide. The 5-year overall survival rate of lung cancer is approximately 20 % due to the delayed diagnosis and low response rate to regular treatments. Microbiota, both host-microbiota and alien pathogenic microbiota, have been investigated to be involved in a complicated and contradictory relationship with lung cancer initiation, treatments, and prognosis. Disorders of certain host-microbiota and pathogen infection are associated with the risk of lung cancers based on epidemiological evidence, and antibiotics (ATBs) could dramatically impair anti-cancer treatment efficacy, including chemotherapy and immunotherapy. Moreover, probiotics and microbe-mediated drugs are potential approaches to enhance regular anti-tumor treatments. Therefore, the knowledge of the complex dual effect of microbes on lung cancer is beneficial to take their essence and remove their dross. This review offers insight into the current trends and advancements in microbiota or microbial components related to lung cancer.

BACKGROUND: Interventional bronchoscopy exhibits substantial effects for patients with malignant airway obstruction (MAO), while little information is available regarding the potential prognostic factors for these patients. METHODS: Between October 31, 2016, and July 31, 2019, a total of 150 patients undergoing interventional bronchoscopy and histologically-confirmed MAO were collected, in which 112 eligible participants formed the cohort for survival study. External validation cohort from another independent institution comprised 33 MAO patients with therapeutic bronchoscopy. The least absolute shrinkage and selection operator regression (LASSO) was applied to the model development dataset for selecting features correlated with MAO survival for inclusion in the Cox regression from which we elaborated the risk score system. A nomogram algorithm was also utilized. RESULTS: In our study, we observed a significant decline of stenosis rate after interventional bronchoscopy from 71.7%±2.1% to 36.6%±2.7% (P

Objective This review was conducted to systematically summarize the progress made by artificial intelligence technology in early screening based medical imaging, pathological diagnosis, genomics inspection, prognostic evaluation, and individual treatment of lung cancer. Background Lung cancer has a high mortality rate in China, which is closely related to the fact that most lung cancer patients are not diagnosed until the malignancy is advanced. Challenges remain in the early detection, accurate diagnosis, monitoring and individual treatment of lung cancers. Artificial intelligence has developed to process large amounts of data, from clinical presentations to physiological images, which is essential for solving the complex issues with clinical medicine. Increasing evidence has suggested that artificial intelligence technology provides novel, promising strategies for the diagnosis and treatment of lung cancer. Methods A review of literature was conducted in PubMed, EMBASE and Cochrane to identify the latest research on artificial intelligence and lung cancer, and ultimately to generate a narrative review. Conclusions Artificial intelligence plays an important role in the imaging inspection, histopathology examination and genomics inspection of lung cancer. In addition, artificial intelligence has the ability to detect a small number of biomarkers, which is conducive to lung cancer monitoring. Moreover, the intelligent treatment of lung cancer has gradually become the trend of future development, whether in internal medicine or surgical treatment. It is believed that artificial intelligence could improve the early diagnosis of lung cancer and assist doctors in treating lung cancer patients individually.

To elucidate the clinicopathological characteristics and oncological outcomes of clinical T1aN0M0 (c-T1N0M0) lung cancer based on the newest 8th TNM classification. A total of 257 patients with c-T1aN0M0 lung cancer were retrospectively included in this study. According to the solid component size manifesting on the high-resolution computed tomography (HRCT), all lesions were classified as the pure ground-glass nodule (pure-GGN) with a diameter > 3 cm (n = 19), part-solid (n = 174), and pure-solid (n = 64) groups. We evaluated the prognostic impact of clinicopathologic variables including radiological presentations by establishing Cox proportional hazards model. When we evaluated the prognostic impact based on the radiological subtypes, the 5-year recurrence-free survival (RFS) and overall survival (OS) were significantly different among pure-GGN, part-solid, and pure-solid groups (RFS: 100% versus 95.4% versus 76.6%, p < 0.0001; OS: 100% versus 98.9% versus 87.5%, p < 0.0001). Cox regression analysis revealed the preoperative carcinoembryonic antigen (CEA) level and consolidation tumor ratio (CTR) were independently significant prognosticators related to RFS and OS. Furthermore, a receiver operating characteristic (ROC) verified the CTR (area under ROC [AUC] 0.784, 95%CI 0.697–0.869) was equipped with good performance to predict the postoperative recurrence with a cutoff point at 0.5. Lung cancer with higher CTR tended to be associated with lower survival in the c-T1aN0M0 stage. For the c-T1aN0M0 lung cancer, pulmonary nodules manifested as the pure-GGN and part-solid subtypes had an excellent prognosis and may be considered as the “early-stage” cancer, whereas those with pure-solid appearance were associated with the high risk of recurrence despite the sub-centimeter size. • Radiological subtypes could further stratify the risk of lung cancer in cT1a. • Sub-solid nodule has a favorable survival in c-T1a lung cancer, whereas pure-solid nodule is not always “early-stage” lung cancer and is relatively prone to postoperative recurrence despite the sub-centimeter size. • The preoperative CEA level and CTR are valuable prognosticators to predict the recurrence in c-T1a lung cancer.

Background Bone metastasis (BoM) is common in patients with advanced non‐small cell lung cancer (NSCLC) and considered as one of the negative prognostic factors. However, the impact of BoM on clinical outcomes of patients with advanced NSCLC treated with immune checkpoint inhibitors (ICIs) remains unclear. Methods A total of 103 patients treated with ICI monotherapy and 101 patients treated with ICIs combined with chemotherapy or antiangiogenesis therapy were retrospectively analyzed. The differences in progression‐free survival (PFS), overall survival (OS) and objective response rate (ORR) between BoM+ and BoM− were investigated. Results Of those 101 patients who received combination therapy, no significant difference between BoM− and BoM+ in terms of both median PFS and median OS (median PFS, 10.1 vs. 12.1 months, P = 0.6; median OS, NR vs. 24.6 months, P = 0.713) was determined. In contrast, of the 103 patients who received ICI monotherapy, BoM+ patients had an inferior PFS (4.2 vs. 6.7 months, P = 0.0484) and OS (12.5 vs. 23.9 months, P = 0.0036) compared with BoM− patients. The univariate and multivariate analysis in the ICI monotherapy group also identified BoM as an independent factor attenuating the efficacy of ICI monotherapy. Of all BoM+ patients who received ICI monotherapy, neither palliative radiotherapy nor bisphosphonate drugs improved OS (palliative radiotherapy: 12.5 vs. 16.7 months, P = 0.487; bisphosphonate drugs: 12.5 vs. 9.7 months, P = 0.568). Conclusions BoM attenuated the efficacy of ICI monotherapy in patients with advanced NSCLC. Of BoM+ patients who received ICI monotherapy, neither palliative radiotherapy nor bisphosphonate drugs improved OS. Other therapeutic strategies are needed for patients with BoM., Bone metastasis is common in patients with advanced non‐small cell lung and considered as one of the negative prognostic factors, but the impact of bone metastases on clinical outcomes of immune checkpoint inhibitors remains unclear. Our study demonstrated that bone metastases attenuated the efficacy of ICIs monotherapy in patients with advanced NSCLC. Of patients with bone metastases who received ICIs monotherapy, neither palliative radiotherapy nor bisphosphonate drugs improved OS.

DNA damage response and repair (DDR) gene alterations increase tumor-infiltrating lymphocytes, genomic instability, and tumor mutational burden (TMB). Whether DDR-related alterations relate to therapeutic response and prognosis in lung cancer lacking oncogenic drivers remains unknown. Pretherapeutic cancer samples of 122 patients [86 non-small cell lung cancer and 36 small cell lung cancer (SCLC)] harboring no EGFR/ALK alterations were collected. Through whole-exome sequencing, we outlined DDR mutational landscape and determined relationships between DDR gene alterations and TMB or intratumoral heterogeneity. Then, we evaluated the impacts of DDR gene alterations on therapeutic response and prognosis and established a DDR-based model for prognosis prediction. In addition, we investigated somatic interactions of DDR genes and immunomodulatory genes, immune expression patterns, immune microenvironment, and immune infiltration characteristics between DDR-deficient and DDR-proficient samples. Samples from cBioportal datasets were utilized for verification. We found that deleterious DDR gene alterations were closely associated with higher TMB than proficient-types (p < 0.001). DDR mechanisms attach great importance to the determination of patients’ prognosis after chemotherapy, and alterations of base excision repair pathway in adenocarcinoma, nucleotide excision repair in squamous carcinoma, and homologous recombination pathway in SCLC tend to associate with worse progression-free survival to first-line chemotherapy (all p < 0.05). A predictive nomogram model was constructed incorporating DDR-related alterations, clinical stage, and smoking status, with the area under curve values of 0.692–0.789 for 1- and 2-year receiver operating characteristic curves in training and testing cohorts. Furthermore, DDR-altered tumors contained enhanced frequencies of alterations in various genes of human leukocyte antigen (HLA) class I pathway including TAP1 and TAP2 than DDR-proficient samples. DDR-deficient types had lower expressions of STING1 (p = 0.01), CD28 (p = 0.020), HLA-DRB6 (p = 0.014) in adenocarcinoma, lower TNFRSF4 (p = 0.017), and TGFB1 expressions (p = 0.033) in squamous carcinoma, and higher CD40 (p = 0.012) and TNFRSF14 expressions (p = 0.022) in SCLC. DDR alteration enhanced activated mast cells in adenocarcinoma (p = 0.044) and M2 macrophage in squamous carcinoma (p = 0.004) than DDR-proficient types. Collectively, DDR gene alterations in lung cancer without oncogenic drivers are positively associated with high TMB. Specific DDR gene alterations tend to associate with worse progression-free survival to initial chemotherapy.

BACKGROUND: Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare clinical subtype of lung cancer which has a poor prognosis for patients. This study aimed to explore the relationship between blood-based inflammatory markers, namely neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), and the prognosis for pulmonary LCNEC. METHODS: Peripheral leukocyte and platelet counts of 106 LCNEC patients were measured within the week leading up to their surgery. Serum neuron specific enolase (NSE) was detected by ELISA. Overall survival (OS) was analyzed by Kaplan-Meier method and compared by log-rank test. RESULTS: The NLR and PLR cut-off values based on survival receiver operating characteristic curve (ROC) were 2.52 and 133.6, respectively. A correlation was found between dichotomized NLR and tumor size (P=0.006), and PLR and NLR were significantly correlated with each other (P

Lung cancer is a highly heterogeneous disease. Cancer cells and cells within the tumor microenvironment together determine disease progression, as well as response to or escape from treatment. To map the cell type-specific transcriptome landscape of cancer cells and their tumor microenvironment in advanced non-small cell lung cancer (NSCLC), we analyze 42 tissue biopsy samples from stage III/IV NSCLC patients by single cell RNA sequencing and present the large scale, single cell resolution profiles of advanced NSCLCs. In addition to cell types described in previous single cell studies of early stage lung cancer, we are able to identify rare cell types in tumors such as follicular dendritic cells and T helper 17 cells. Tumors from different patients display large heterogeneity in cellular composition, chromosomal structure, developmental trajectory, intercellular signaling network and phenotype dominance. Our study also reveals a correlation of tumor heterogeneity with tumor associated neutrophils, which might help to shed light on their function in NSCLC., Comprehensive profiles of tumour and microenvironment are critical to understand heterogeneity in non-small cell lung cancer (NSCLC). Here, the authors profile 42 late-stage NSCLC patients with single-cell RNA-seq, revealing immune landscapes that are associated with cancer subtype or heterogeneity.

BackgroundImmunotherapies may prolong the survival of patients with small-cell lung cancer (SCLC) to some extent. The role of forkhead box protein P3 (FOXP3) in tumor microenvironment (TME) remains controversial. We aimed to examine FOXP3-related expression characteristics and prognostic values and to develop a clinically relevant predictive system for SCLC.MethodsWe enrolled 102 patients with histologically confirmed SCLC at stages I–III. Through immunohistochemistry, we determined the expression pattern of FOXP3 and its association with other immune biomarkers. By machine learning and statistical analysis, we constructed effective immune risk score models. Furthermore, we examined FOXP3-related enrichment pathways and TME traits in distinct cohorts.ResultsIn SCLC, FOXP3 level was significantly associated with status of programmed death-ligand 1 (PD-L1), programmed cell death protein 1 (PD-1), CD4, CD8, and CD3 (p=0.002, p=0.001, p=0.002, p=0.030, and pCD28, basic excision repair genes MUTYH, POLD1, POLD2, and oxidative phosphorylation related gene cytochrome c oxidase subunit 8A with FOXP3 expression were revealed. Moreover, we found low-immune risk score group had statistically higher activated CD4+ memory T cells (p=0.014) and plasma cells (p=0.049) than the high-risk group. The heterogeneity of tumor-infiltrating immune cells might represent a promising feature for risk prediction in SCLC.ConclusionFOXP3 interacts closely with immune biomarkers on tumor-infiltrating cells in TME. This study highlighted the crucial prognostic value and promising clinical applications of FOXP3 in SCLC.

Background Recent studies have suggested obesity could contribute to improved outcomes of immune checkpoint inhibitor (ICI)-based treatment. Non-alcoholic fatty liver disease (NAFLD), the most common form of chronic liver disease, is also obesity-related, but its association with the efficacy of ICI-based treatment has not yet been reported. Methods We retrospectively reviewed the medical records of advanced non-small cell lung cancer (NSCLC) patients treated at Shanghai Pulmonary Hospital between June 2015 and June 2019. NAFLD was confirmed by ultrasound examination of the abdomen. The efficacy of ICI-based treatment was evaluated based on Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). Univariate analysis to compare progression-free survival (PFS) was conducted using the log-rank test. Multivariate analysis was performed using the Cox proportional hazards model. Results A total of 223 patients with advanced NSCLC who received ICI-based treatment were included in the study, of whom 26.9% (n=60) were confirmed to have NAFLD. Patients with NAFLD were more inclined to to have non-squamous carcinoma and higher body mass index (BMI) compared with those without NAFLD. The median PFS of the entire cohort of patients was 6.6 months. Nno significant difference was found in response [objective response rate (ORR) 43.3% vs. 35.6%, P=0.289, disease control rate (DCR) 83.3% vs. 75.5%, P=0.211], nor in PFS (7.0 vs. 6.6 months, P=0.769) between the patients with (n=60) and without NAFLD (n=163). Surprisingly, in the subgroup of patients with liver metastases (LMs), there were dramatically significant differences in ORR (71.4% vs. 9.1%, P=0.013), DCR (85.7% vs. 18.2%, P=0.013), and median PFS [5.1 vs. 2.1 months, P=0.014, hazard ratio (HR): 0.244] between patients with (n=7) and without (n=11) NAFLD. Multivariate analysis revealed NAFLD to have a significant impact on PFS (P=0.017) in patients with LMs. In addition, the DCR of LMs was significantly higher in patients with NAFLD compared to those who did not have NAFLD (DCR: 42.9% vs. 0.0%, P=0.038). Conclusions In conclusion, NAFLD holds no clinical benefit for advanced NSCLC patients who undergo ICI-based treatment, but it is associated with improved outcomes in patients with LMs.