Small Cell Lung
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2021 ◽  
Ming Zhang ◽  
Hualiang Zhang ◽  
Linfeng Cao ◽  
Gouxin Hou ◽  
Chao Lu ◽  

Abstract Background As mRNA binding proteins, MEX3 (muscle excess 3) family highlights its unique characteristics and plays an emerging role in post-transcriptionally regulating programmed of biological processes, including tumor cell death and immunological relevance. These have been shown to be involved in various diseases, however, the role of MEX3 in non-small-cell lung cancer (NSCLC) has not been fully elucidated. Results In this study, we found that the sequence or copy number of MEX3 gene did not change significantly, which can explain the stability of malignant tumor development through the COSMIC database. Further, gene expression in NSCLC was examined using the Oncomine™ database, and the prognostic value of each gene was analyzed by Kaplan-Meier analysis. The results showed that overexpressed of MEX3A, MEX3B, MEX3C and MEX3D were associated with significantly lower OS in patients with NSCLC and LUAD, while overexpressed of MEX3D was associated with significantly poorer OS in patients with LUSC. We also applied the Tumor Immune Estimation Resource (TIMER) tool to assess the correlations between distinct MEX3 and the infiltrating immune cell landscape. Conclusion On this subject, we have learned about the complexity and heterogeneity of NSCLC through MEX3. We found that most of MEX3 is highly expressed in NSCLC. High expression indicates a poor prognosis and has a certain immune correlation. Therefore, these conclusions can lay a framework for the prognosis of NSCLC patients and the development of treatment strategies in the future.

2021 ◽  
Miyako Satouchi ◽  
Kaname Nosaki ◽  
Toshiaki Takahashi ◽  
Kazuhiko Nakagawa ◽  
Keisuke Aoe ◽  

Mehdi Amini ◽  
Mostafa Nazari ◽  
Isaac Shiri Lord ◽  
Ghasem Hajianfar ◽  
Mohammad reza Deevband ◽  

Acta Medica ◽  
2021 ◽  
pp. 1-8
Nese Unver

Objective: Non-Small Cell Lung Cancer has a high incidence and great clinical importance as the cancer subtype with the highest mortality. It is necessary to investigate cytokines associated with the Programmed death-ligand 1, one of the immunotherapeutic target molecules, in KRas mutant lung cancer cells. Materials and Methods: In this study, the expression of Programmed death-ligand 1 as well as pro-inflammatory interleukins was evaluated in 44 lung cancer cell lines harboring KRas mutations and RNAseq expression data of lung adenocarcinoma patients and correlation analyses were performed. Macrophages and dendritic cells, the major immune cells associated with Interleukin-1, Interleukin-6, Interleukin-12 and Interleukin-23, were also evaluated. Results: In KRas mutant lung cancer cells and lung adenocarcinoma tissues, expression of cytokines Interleukin-1A, Interleukin-6, Interleukin-12 and Interleukin-23 showed a positive correlation with Programmed death-ligand 1 expression (p≤0.05). The quantity of M1 macrophages and dendritic cells, both of which are cytokine-producing immune cells, is less in KRas mutant lung cancer tissues than non-mutants. Conclusion: Detailed studies in clinical samples, especially in blood, primary, and metastatic tissues, will help to create and validate cytokine panels that can be used in therapeutic targeting of KRas mutant subtype lung cancer with high Programmed death-ligand 1 expression.

2021 ◽  
Lihu Gu ◽  
Jiali Liang ◽  
Wei Dai ◽  
Jiayu Li ◽  
Yuexiu Si ◽  

Abstract Background: In spite of the wide use of immune-checkpoint inhibitors (ICIs) in advanced or metastatic non-small cell lung cancer (NSCLC), whether ICIs or conventional chemotherapy is more effective still remains controversial. This study was conducted to evaluate the efficacy of giving patients programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1), or cytotoxic T-lymphocyte protein 4 (CTLA-4) alone or in their combination (PD-1/L1 + CTLA-4) versus simply applying chemotherapy in patients with advanced or metastatic NSCLC.Methods: This meta-analysis was conducted from PubMed, Web of Science, Medline, Embase, and the Cochrane Library up to March 2021 to identify relevant randomized controlled trials (RCTs). Primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoint was adverse events (AEs). Results: The search process has identified 13 studies containing 7918 patients with advanced or metastatic NSCLC. The benefit of PD-1/L1 or CTLA-4 inhibitors alone or in combination compared with chemotherapy for advanced or metastatic NSCLC was elucidated in both overall survival (OS) [HR=0.75, 95%CI (0.70-0.80), P<0.001] and progression-free survival (PFS) [HR=0.83, 95%CI (0.73-0.95), P<0.001]. Sex is another vital factor that affects the efficacy of ICIs. Male [HR=0.71, 95%CI (0.63-0.81)] benefits more from ICIs than the female [HR 0.80, 95%CI (0.68-0.94)] in OS. Besides, ICIs were associated with fewer AEs compared to chemotherapy.Conclusion: PD-1/L1 or CTLA-4 inhibitors alone or in combination, with fewer AEs, was associated with significant improvements in terms of OS and PFS than chemotherapy in treatment of advanced or metastatic NSCLC.

2021 ◽  
Vol 12 ◽  
Yuanyuan Chang ◽  
Yin Wang ◽  
Boyi Li ◽  
Xingzhong Lu ◽  
Ruiru Wang ◽  

Circulating tumor cells (CTCs) have important applications in clinical practice on early tumor diagnosis, prognostic prediction, and treatment evaluation. Platinum-based chemotherapy is a fundamental treatment for non-small cell lung cancer (NSCLC) patients who are not suitable for targeted drug therapies. However, most patients progressed after a period of treatment. Therefore, revealing the genetic information contributing to drug resistance and tumor metastasis in CTCs is valuable for treatment adjustment. In this study, we enrolled nine NSCLC patients with platinum-based chemotherapy resistance. For each patient, 10 CTCs were isolated when progression occurred to perform single cell–level whole-exome sequencing (WES). Meanwhile the patients’ paired primary-diagnosed formalin-fixed and paraffin-embedded samples and progressive biopsy specimens were also selected to perform WES. Comparisons of distinct mutation profiles between primary and progressive specimens as well as CTCs reflected different evolutionary mechanisms between CTC and lymph node metastasis, embodied in a higher proportion of mutations in CTCs shared with paired progressive lung tumor and hydrothorax specimens (4.4–33.3%) than with progressive lymphatic node samples (0.6–11.8%). Functional annotation showed that CTCs not only harbored cancer-driver gene mutations, including frequent mutations of EGFR and TP53 shared with primary and/or progressive tumors, but also particularly harbored cell cycle–regulated or stem cell–related gene mutations, including SHKBP1, NUMA1, ZNF143, MUC16, ORC1, PON1, PELP1, etc., most of which derived from primary tumor samples and played crucial roles in chemo-drug resistance and metastasis for NSCLCs. Thus, detection of genetic information in CTCs is a feasible strategy for studying drug resistance and discovering new drug targets when progressive tumor specimens were unavailable.

2021 ◽  
pp. 20210776
Joanna Socha ◽  
Ewa Wasilewska-Teśluk ◽  
Rafal Stando ◽  
Lukasz Kuncman ◽  
Lucyna Kepka

Objectives: In our previous prospective trial on accelerated hypofractionated concomitant radiochemotherapy (AHRT-CHT) for non-small-cell lung cancer (NSCLC) the incidence of grade ≥3 acute esophageal toxicity (AET) was similar to that reported for conventionally fractionated concomitant radiochemotherapy (CFRT-CHT), but its duration was prolonged. Thus, we aimed to compare the duration of grade ≥3 AET between AHRT-CHT and CFRT-CHT. Methods: Clinical data of 76 NSCLC patients treated with CFRT-CHT (60–66 Gy/2 Gy) during 2015–2020 were retrospectively compared with the data of 92 patients treated with AHRT-CHT (58.8 Gy/2.8 Gy) in the prospective trial. The maximum grade of AET, incidence, and duration of grade ≥3 AET were the endpoints. Univariate and multivariate analyses were applied to correlate clinical and treatment variables with these endpoints. Results: Neither the maximum grade of AET (p = 0.71), nor the incidence of grade ≥3 AET (p = 0.87) differed between the two groups. The number of CHT cycles delivered (2 vs 1, p = 0.005) and higher esophagus mean BED (p = 0.009) were significant predictors for a higher maximum grade of AET; older age was a significant predictor for higher incidence of grade ≥3 AET (p = 0.03). The median duration of grade≥3 AET in AHRT-CHT and CFRT-CHT group was 30 days (range 5-150) vs 7 days (range 3-20), respectively, p = 0.0005. In multivariate analysis, only the AHRT-CHT schedule (p=0.003) was a significant predictor for a longer duration of grade≥3 AET. Conclusions Despite similar incidence of grade≥3 AET, its duration is significantly prolonged in NSCLC patients treated with AHRT-CHT compared to CFRT-CHT. Advances in knowledge Reporting only the rate of grade≥3 AET in clinical trials may underestimate the real extent of the esophageal toxicity; its duration should also be routinely reported.

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