Search

In recent decades, multiple primary lung cancer (MPLC) has been increasingly prevalent in clinical practice. However, many details about MPLC have not been completely settled, such as understanding the driving force, clinical management, pathological mechanisms, and genomic architectures of this disease. From the perspective of diagnosis and treatment, distinguishing MPLC from lung cancer intrapulmonary metastasis (IPM) has been a clinical hotpot for years. Besides, compared to patients with single lung lesion, the treatment for MPLC patients is more individualized, and non-operative therapies, such as ablation and stereotactic ablative radiotherapy (SABR), are prevailing. The emergence of next-generation sequencing has fueled a wave of research about the molecular features of MPLC and advanced the NCCN guidelines. In this review, we generalized the latest updates on MPLC from definition, etiology and epidemiology, clinical management, and genomic updates. We summarized the different perspectives and aimed to offer novel insights into the management of MPLC.

The role and mechanism of transmembrane proteins (TMEMs) in tumorigenesis remain unclear. Based on 4 independent cohorts containing 1,208 cases, we identified 3 TMEMs (TMEM273, TMEM164, and TMEM125), which were used to construct a risk model to predict the prognosis of LUAD. The two patterns based on the risk score exhibited a high degree of consistency with the characteristics of immune cell infiltration and epigenetic distribution. Patients with a low-risk score, characterized by an increased activation of immunity, H3K4me3 modification, tumor cell apoptosis, chemokine secretion, and TMB, had better disease-free survival (DFS) and overall survival (OS). Obvious immunosuppression, increased epithelial–mesenchymal transition, a low H3K4me3 level, shortened cell cycle, and accelerated cell division manifested in high-risk patients, with poorer DFS and OS. The model showed a better prognostic value than the tumor immune dysfunction and exclusion score. Correlation analysis told us that patients with high scores were suitable for treatment with CD276 inhibitors for their higher levels of CD276 expression. The risk score had a strong negative correlation with HAVCR2 and ICOS among patients with EGFR-WT, KRAS-WT, STK11-WT, or TP53-MUT, and patients with these mutation types with low scores were suitable for treatment with HAVCR2 or ICOS inhibitors. This work comprehensively analyzed the role and mechanism of TMEMs in LUAD and revealed the characteristics of histone methylation modification. The TMEM-based signature gave us deep insight into immune cell infiltration profiles and provided an individualized immunotherapy strategy.

Metabolic reprogramming is a hallmark of malignancy. Understanding the characteristics of metabolic reprogramming in esophageal squamous cell carcinoma (ESCC) helps uncover novel targets for cancer progression. In this study, 880 metabolism-related genes were identified from microarray data and then filtered to divide patients into two subgroups using consensus clustering, which exhibits significantly different overall survival. After a differential analysis between two subtypes, 3 genes were screened out to construct a two subtypes decision model on the training cohort (GSE53624), defined as high-risk and low-risk subtypes. These risk models were then verified in two public databases (GSE53622 and TCGA-ESCC), an independent cohort of 49 ESCC patients by RT-qPCR and an external cohort of 95 ESCC patients by immunohistochemistry analysis (IHC). Furthermore, the immune cell infiltration of regulatory T cells (Tregs) and plasma cells showed a significant difference between the high and low-risk subtypes in the IHC experiment with 119 ESCC patients. In conclusion, our study indicated that three metabolism-related prognostic genes could stratify patients into subgroups and were associated with immune infiltration, clinical features and clinical outcomes.

Bladder urothelial carcinoma (BC) is a fatal invasive malignancy and the most common malignancy of the urinary system. In the current study, we investigated the function and mechanisms of Neuropilin-1 (NRP1), the co-receptor for vascular endothelial growth factor, in BC pathogenesis and progression. The expression of NRP1 was evaluated using data extracted from GEO and HPA databases and examined in BC cell lines. The effect on proliferation, apoptosis, angiogenesis, migration, and invasion of BC cells were validated after NRP1 knockdown. After identifying differentially expressed genes (DEGs) induced by NRP1 silencing, GO/KEGG and IPA® bioinformatics analyses were performed and specific predicted pathways and targets were confirmed in vitro. Additionally, the co-expressed genes and ceRNA network were predicted using data downloaded from CCLE and TCGA databases, respectively. High expression of NRP1 was observed in BC tissues and cells. NRP1 knockdown promoted apoptosis and suppressed proliferation, angiogenesis, migration, and invasion of BC cells. Additionally, after NRP1 silencing the activity of MAPK signaling and molecular mechanisms of cancer pathways were predicted by KEGG and IPA® pathway analysis and validated using western blot in BC cells. NRP1 knockdown also affected various biological functions, including antiviral response, immune response, cell cycle, proliferation and migration of cells, and neovascularisation. Furthermore, the main upstream molecule of the DEGs induced by NRP1 knockdown may be NUPR1, and NRP1 was also the downstream target of NUPR1 and essential for regulation of FOXP3 expression to activate neovascularisation. DCBLD2 was positively regulated by NRP1, and PPAR signaling was significantly associated with low NRP1 expression. We also found that NRP1 was a predicted target of miR-204, miR-143, miR-145, and miR-195 in BC development. Our data provide evidence for the biological function and molecular aetiology of NRP1 in BC and for the first time demonstrated an association between NRP1 and NUPR1, FOXP3, and DCBLD2. Specifically, downregulation of NRP1 contributes to BC progression, which is associated with activation of MAPK signaling and molecular mechanisms involved in cancer pathways. Therefore, NRP1 may serve as a target for new therapeutic strategies to treat BC and other cancers.

As extracellular vesicles, exosomes are released from most cells to perform cell–cell communication. Recent studies have shown that exosomes could be released into tumor microenvironment and blood to promote tumor progression through packaging and transmitting various bioactive molecules, such as cholesterol, proteins, lipids, miRNAs, mRNAs, and long non-coding RNAs (lncRNAs) to distant cells. LncRNAs have emerged as a major class of non-coding transcripts. A lot of LncRNAs have been discovered during the past few years of research on genomics. They have been proven to participate in various biological functions and disease processes through multiple mechanisms. In this review, we analyzed the role of exosome-derived lncRNAs in lung carcinogenesis and metastasis. We also highlight opportunities for the clinical potential of exosomes with specific lncRNAs as biomarkers and therapeutic intervention in lung cancer.

Background: Lobectomy with mediastinal lymph node dissection has always been recognized as the standardized treatment for early-stage non-small-cell lung cancer. However, the feasibility of segmentectomy performed in stage IB non-small-cell lung cancer (NSCLC) patients remains controversial. The present study aims to investigate whether the outcome of stage IB NSCLC patients undergoing segmentectomy was comparable to those who underwent lobectomy.Method: We retrospectively collected data of 11,010 patients with primary stage IB non-small-cell lung cancer from the Surveillance, Epidemiology, and End Results database. Overall survival (OS) and lung cancer-specific survival (LCSS) were assessed among patients who were performed lobectomy or segmentectomy. To further assess the impact of the surgical procedures on patients with different tumor sizes, subgroups stratified by tumor size were analyzed.Results: A total of 11,010 patients who were pathologically confirmed to be stage IB were included, of whom 10,453 received lobectomy and 557 received segmentectomy. Both univariate and multivariate Cox regression analyses showed that the patients receiving lobectomy had better OS [hazards ratio (HR) = 1.197, 95% confidence interval (CI) (1.066, 1.343), P < 0.001] than those receiving segmentectomy. However, multivariate analysis showed that there was no significant difference in LCSS between lobectomy and segmentectomy [HR = 1.172, 95% CI (0.963, 1.427), P = 0.114]. Meanwhile, subgroup analyses showed that lobectomy rather than segmentectomy was associated with better OS [HR = 1.278, 95% CI (1.075, 1.520) P = 0.006] and LCSS [HR = 1.118, 95% CI (1.005, 1.280), P = 0.047] for patients with a tumor size (TS) of ≤ 40 and >30 mm, while for patients with a TS of ≤ 30 mm, lobectomy yielded similar OS [TS ≤ 20 mm: HR = 1.068, 95% CI (0.853, 1.336), P = 0.566; TS > 20 mm and ≤ 30 mm: HR = 1.195, 95% CI (0.961, 1.487), P = 0.109] and LCSS [TS ≤ 20 mm: HR = 1.029, 95% CI: (0.682, 1.552), P = 0.893; TS > 20 and ≤ 30 mm: HR = 1.144, 95% CI (0.795, 1.645), P = 0.469] to that of segmentectomy.Conclusion: Segmentectomy achieved equivalent OS and LCSS in stage IB NSCLC patients with TS ≤ 30 mm compared with lobectomy. Lobectomy showed better OS and LCSS than segmentectomy for patients with a TS of >30 and ≤ 40 mm. Segmentectomy may be acceptable in patients with an older age and a smaller TS.

The role and mechanism of transmembrane proteins (TMEMs) in tumorigenesis remain unclear. Based on 4 independent cohorts containing 1,208 cases, we identified 3 TMEMs (TMEM273, TMEM164, and TMEM125), which were used to construct a risk model to predict the prognosis of LUAD. The two patterns based on the risk score exhibited a high degree of consistency with the characteristics of immune cell infiltration and epigenetic distribution. Patients with a low-risk score, characterized by an increased activation of immunity, H3K4me3 modification, tumor cell apoptosis, chemokine secretion, and TMB, had better disease-free survival (DFS) and overall survival (OS). Obvious immunosuppression, increased epithelial–mesenchymal transition, a low H3K4me3 level, shortened cell cycle, and accelerated cell division manifested in high-risk patients, with poorer DFS and OS. The model showed a better prognostic value than the tumor immune dysfunction and exclusion score. Correlation analysis told us that patients with high scores were suitable for treatment with CD276 inhibitors for their higher levels of CD276 expression. The risk score had a strong negative correlation with HAVCR2 and ICOS among patients with EGFR-WT, KRAS-WT, STK11-WT, or TP53-MUT, and patients with these mutation types with low scores were suitable for treatment with HAVCR2 or ICOS inhibitors. This work comprehensively analyzed the role and mechanism of TMEMs in LUAD and revealed the characteristics of histone methylation modification. The TMEM-based signature gave us deep insight into immune cell infiltration profiles and provided an individualized immunotherapy strategy. [ABSTRACT FROM AUTHOR]

Metabolic reprogramming is a hallmark of malignancy. Understanding the characteristics of metabolic reprogramming in esophageal squamous cell carcinoma (ESCC) helps uncover novel targets for cancer progression. In this study, 880 metabolism-related genes were identified from microarray data and then filtered to divide patients into two subgroups using consensus clustering, which exhibits significantly different overall survival. After a differential analysis between two subtypes, 3 genes were screened out to construct a two subtypes decision model on the training cohort (GSE53624), defined as high-risk and low-risk subtypes. These risk models were then verified in two public databases (GSE53622 and TCGA-ESCC), an independent cohort of 49 ESCC patients by RT-qPCR and an external cohort of 95 ESCC patients by immunohistochemistry analysis (IHC). Furthermore, the immune cell infiltration of regulatory T cells (Tregs) and plasma cells showed a significant difference between the high and low-risk subtypes in the IHC experiment with 119 ESCC patients. In conclusion, our study indicated that three metabolism-related prognostic genes could stratify patients into subgroups and were associated with immune infiltration, clinical features and clinical outcomes. [ABSTRACT FROM AUTHOR]

Noncoding ribonucleic acids (ncRNAs) are closely associated with tumor initiation, growth, and progress in lung cancer. Long ncRNAs (lncRNAs), as one of the three subclasses of ncRNAs, play important roles in chromatin modification, transcription, and post-transcriptional processing. Various lncRNAs have recently been reported to be dysfunctional or dysregulated in cancers and have pro- or anti-tumor potential. Importantly, as a new class of cancer biomarkers, studies have demonstrated the plausibility of using certain subsets of lncRNAs as promising diagnostic, therapeutic, or prognostic strategies to manage cancers. This review focuses on lncRNAs associated with hallmarks of lung cancer, especially those discovered in the last five years. The expression levels of these lncRNAs in tumor samples are discussed, alongside their mechanisms of action, drug resistance, and potential as diagnostic and prognostic markers for lung cancer. [ABSTRACT FROM AUTHOR]

As extracellular vesicles, exosomes are released from most cells to perform cell–cell communication. Recent studies have shown that exosomes could be released into tumor microenvironment and blood to promote tumor progression through packaging and transmitting various bioactive molecules, such as cholesterol, proteins, lipids, miRNAs, mRNAs, and long non-coding RNAs (lncRNAs) to distant cells. LncRNAs have emerged as a major class of non-coding transcripts. A lot of LncRNAs have been discovered during the past few years of research on genomics. They have been proven to participate in various biological functions and disease processes through multiple mechanisms. In this review, we analyzed the role of exosome-derived lncRNAs in lung carcinogenesis and metastasis. We also highlight opportunities for the clinical potential of exosomes with specific lncRNAs as biomarkers and therapeutic intervention in lung cancer. [ABSTRACT FROM AUTHOR]

Background: Lobectomy with mediastinal lymph node dissection has always been recognized as the standardized treatment for early-stage non-small-cell lung cancer. However, the feasibility of segmentectomy performed in stage IB non-small-cell lung cancer (NSCLC) patients remains controversial. The present study aims to investigate whether the outcome of stage IB NSCLC patients undergoing segmentectomy was comparable to those who underwent lobectomy. Method: We retrospectively collected data of 11,010 patients with primary stage IB non-small-cell lung cancer from the Surveillance, Epidemiology, and End Results database. Overall survival (OS) and lung cancer-specific survival (LCSS) were assessed among patients who were performed lobectomy or segmentectomy. To further assess the impact of the surgical procedures on patients with different tumor sizes, subgroups stratified by tumor size were analyzed. Results: A total of 11,010 patients who were pathologically confirmed to be stage IB were included, of whom 10,453 received lobectomy and 557 received segmentectomy. Both univariate and multivariate Cox regression analyses showed that the patients receiving lobectomy had better OS [hazards ratio (HR) = 1.197, 95% confidence interval (CI) (1.066, 1.343), P < 0.001] than those receiving segmentectomy. However, multivariate analysis showed that there was no significant difference in LCSS between lobectomy and segmentectomy [HR = 1.172, 95% CI (0.963, 1.427), P = 0.114]. Meanwhile, subgroup analyses showed that lobectomy rather than segmentectomy was associated with better OS [HR = 1.278, 95% CI (1.075, 1.520) P = 0.006] and LCSS [HR = 1.118, 95% CI (1.005, 1.280), P = 0.047] for patients with a tumor size (TS) of ≤ 40 and >30 mm, while for patients with a TS of ≤ 30 mm, lobectomy yielded similar OS [TS ≤ 20 mm: HR = 1.068, 95% CI (0.853, 1.336), P = 0.566; TS > 20 mm and ≤ 30 mm: HR = 1.195, 95% CI (0.961, 1.487), P = 0.109] and LCSS [TS ≤ 20 mm: HR = 1.029, 95% CI: (0.682, 1.552), P = 0.893; TS > 20 and ≤ 30 mm: HR = 1.144, 95% CI (0.795, 1.645), P = 0.469] to that of segmentectomy. Conclusion: Segmentectomy achieved equivalent OS and LCSS in stage IB NSCLC patients with TS ≤ 30 mm compared with lobectomy. Lobectomy showed better OS and LCSS than segmentectomy for patients with a TS of >30 and ≤ 40 mm. Segmentectomy may be acceptable in patients with an older age and a smaller TS. [ABSTRACT FROM AUTHOR]