scholarly journals Gene Characteristics and Prognostic Values of m6A RNA Methylation Regulators in Nonsmall Cell Lung Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Na Li ◽  
Xiaojuan Chen ◽  
Yanhong Liu ◽  
Tieming Zhou ◽  
Wei Li
Keyword(s):  
Lung Cancer ◽  
Mrna Expression ◽  
Cell Lung Cancer ◽  
Copy Number ◽  
Prognostic Significance ◽  
Nonsmall Cell Lung Cancer ◽  
Genetic Alterations ◽  
Regulatory Genes ◽  
Copy Number Loss ◽  
Nsclc Patients

Background. N6-methyladenosine (m6A) is the most common internal modification present in mRNAs and long noncoding RNAs (lncRNAs), associated with tumorigenesis and cancer progression. However, little is known about the roles of m6A and its regulatory genes in nonsmall cell lung cancer (NSCLC). Here, we systematically explored the roles and prognostic significance of m6A-associated regulatory genes in NSCLC. Methods. The copy number variation (CNV), mutation, mRNA expression data, and corresponding clinical pathology information of 1057 NSCLC patients were downloaded from the cancer genome atlas (TCGA) database. The gain and loss levels of CNVs were determined by utilizing segmentation analysis and GISTIC algorithm. The GSEA was conducted to explore the functions related to different levels of m6A regulatory genes. Logrank test was utilized to assess the prognostic significance of m6A-related gene’s CNV. Results. The genetic alterations of ten m6A-associated regulators were identified in 102 independent NSCLC samples and significantly related to advanced tumor stage. Deletions or shallow deletions corresponded to lower mRNA expression while copy number gains or amplifications were related to increased mRNA expression of m6A regulatory genes. Survival analysis showed the patients with copy number loss of FTO with worse disease-free survival (DFS) or overall survival (OS). Besides, copy number loss of YTHDC2 was also with poor OS for NSCLC patients. Moreover, high FTO expression was significantly associated with oxidative phosphorylation, translation, and metabolism of mRNA. Conclusion. Our findings provide novel insight for better understanding of the roles of m6A regulators and RNA epigenetic modification in the pathogenesis of NSCLC.

Prognostic significance of p53 andras p21 expression in nonsmall cell lung cancer

Cancer ◽  
1995 ◽  
Vol 76 (12) ◽  
pp. 2457-2463 ◽  
Author(s):  
Michihiro Fujino ◽  
Hirotoshi Dosaka-Akita ◽  
Masao Harada ◽  
Hiromitsu Hiroumi ◽  
Ichiro Kinoshita ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Lung Cancer ◽  
Prognostic Significance ◽  
Nonsmall Cell Lung Cancer

scholarly journals The Predictive Efficacy of Tumor Mutation Burden (TMB) on Nonsmall Cell Lung Cancer Treated by Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Zhang Nan ◽  
Wang Guoqing ◽  
Yu Xiaoxu ◽  
Mi Yin ◽  
He Xin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Systematic Review ◽  
Cell Lung Cancer ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Nonsmall Cell Lung Cancer ◽  
Tumor Mutation Burden ◽  
Mutation Burden ◽  
Nsclc Patients

Background. Nonsmall cell lung cancer (NSCLC) is the most common type of lung cancer, and the majority of NSCLC patients are diagnosed at the advanced stage. Chemotherapy is still the main treatment at present, and the overall prognosis is poor. In recent years, immunotherapy has developed rapidly. Immune checkpoint inhibitors (ICIs) as the representative have been extensively applied for treating various types of cancers. Tumor mutation burden (TMB) as a potential biomarker is used to screen appropriate patients for treatment of ICIs. To verify the predictive efficacy of TMB, a systematic review and meta-analysis were conducted to explore the association between TMB and ICIs. Method. PubMed, EMBASE, Cochrane Library, and son on were systematically searched from inception to April 2020. Objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were estimated. Results. A total of 11 studies consisting of 1525 nonsmall cell lung cancer (NSCLC) patients were included. Comparison of high and low TMB: pooled HRs for OS, 0.57 (95% CI 0.32 to 0.99; P = 0.046 ); PFS, 0.48 (95% CI 0.33 to 0.69; P < 0.001 ); ORR, 3.15 (95% CI 2.29 to 4.33; P < 0.001 ). Subgroup analysis values: pooled HRs for OS, 0.75 (95% CI 0.29 to 1.92, P = 0.548 ) for blood TMB (bTMB), 0.44 (95% CI 0.26 to 0.75, P = 0.003 ) for tissue TMB (tTMB); for PFS, 0.54 (95% CI 0.29 to 0.98, P = 0.044 ) and 0.43 (95% CI 0.26 to 0.71, P = 0.001 ), respectively. Conclusions. These findings imply that NSCLC patients with high TMB possess significant clinical benefits from ICIs compared to those with low TMB. As opposed to bTMB, tTMB was thought more appropriate for stratifying NSCLC patients for ICI treatment.

scholarly journals Circulating mRNA Expression of astrocyte-Elevated Gene-1 Associated with Treatment Response and Survival in Non-Small Cell Lung Cancer Patients Treated with Pemetrexed

2021 ◽  
Author(s):  
You-Lung Chang ◽  
Yen-Fu Chen ◽  
Ying-Yin Chen ◽  
Shih-Chieh Chang ◽  
Cheng-Yu Chang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Mrna Expression ◽  
Treatment Response ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cox Regression Analysis ◽  
Nsclc Patients

Abstract Backgrounds: Astrocyte-elevated gene-1 (AEG-1) functions as an oncogene and regulates angiogenesis in non-small cell lung cancer (NSCLC). In this prospective study, we assessed the values of plasma AEG-1 mRNA expression by liquid biopsy associated with tumor response and survival in NSCLC patients treated with pemetrexed. Methods: Patients diagnosed advanced NSCLC were enrolled to be treated with pemetrexed combined platinum as first-line chemotherapy. All patients underwent blood sampling before any cancer treatment (C0) and at first response evaluation after two cycles (C2) treatments. Response to chemotherapy and survival were assessed. Plasma mRNA was extracted from peripheral blood mononuclear cell (PBMC) and quantification of RNA was performed by real-time PCR.Results: A total of 50 patients with advanced NSCLC were included and 13 of 50 patients combined with bevacizumab. In patient groups of SD (n = 13) and PD (n = 10), the plasma mRNA of AEG-1, thymidylate synthase (TS) and CK19 were elevated significantly at C2 compared to patients in treatment response group (PR, n = 27) (PR v.s. SD or PD, AEG-1: 1.22 ± 0.80 v.s. 4.51 ± 15.45, p = 0.043). NSCLC patients had elevated AEG-1 (AEG-1 ≥ 2) after 2-cycle chemotherapy had shorter PFS and OS (high AEG-1 v.s. low AEG-1, median, PFS: 5.5 v.s. 11.9 months, p = 0.021; OS: 25.9 v.s. 40.8 months, p = 0.019, respectively). In Cox regression analysis, increased plasma mRNA expression of AEG-1indicated poor prognosis in survival.Conclusion: Circulating mRNA concentration of AEG-1 could be a predictive and prognostic biomarker in NSCLC patients treated with pemetrexed. Increased expression of AEG-1 contributed to the chemoresistance and caused lung cancer progression.

scholarly journals Role of Immunotherapy for Oncogene-Driven Non-Small Cell Lung Cancer

Cancers ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 245 ◽  
Author(s):  
Yosuke Miura ◽  
Noriaki Sunaga
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Checkpoint Inhibitors ◽  
Genetic Alterations ◽  
Small Cell ◽  
Small Cell Lung ◽  
Future Direction ◽  
Nsclc Patients

The clinical application of immune checkpoint inhibitors (ICIs) has led to dramatic changes in the treatment strategy for patients with advanced non-small cell lung cancer (NSCLC). Despite the observation of improved overall survival in NSCLC patients treated with ICIs, their efficacy varies greatly among different immune and molecular profiles in tumors. Particularly, the clinical significance of ICIs for oncogene-driven NSCLC has been controversial. In this review, we provide recent clinical and preclinical data focused on the relationship between oncogenic drivers and immunological characteristics and discuss the future direction of immunotherapy in NSCLC patients harboring such genetic alterations

scholarly journals Prognostic Significance of Stromal Periostin Expression in Non-Small Cell Lung Cancer

2020 ◽  
Vol 21 (19) ◽  
pp. 7025
Author(s):  
Katarzyna Ratajczak-Wielgomas ◽  
Alicja Kmiecik ◽  
Jedrzej Grzegrzołka ◽  
Aleksandra Piotrowska ◽  
Agnieszka Gomulkiewicz ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Prognostic Factor ◽  
Small Cell Lung Cancer ◽  
Mrna Expression ◽  
Cancer Cells ◽  
Cell Lung Cancer ◽  
Prognostic Significance ◽  
Immunohistochemical Analysis ◽  
Small Cell ◽  
Small Cell Lung

Background: The microenvironment of solid tumours is significant in cancer development and progression. The aim of this study was to determine periostin (POSTN) expression by cancer-associated fibroblasts (CAFs) in non-small-cell lung cancer (NSCLC), as well as to assess associations with clinicopathological factors and prognosis. Materials and Methods: Immunohistochemical analysis of POSTN expression was performed on NSCLC (N = 700) and non-malignant lung tissue (NMLT) (N = 110) using tissue microarrays. Laser capture microdissection (LCM) for isolation of stromal and cancer cells of NSCLC was employed, and subsequently, POSTN mRNA expression was detected by real-time PCR. Immunofluorescence reaction and colocalisation analysis were performed by confocal microscopy. Results: Expression of POSTN in CAFs was significantly higher in NSCLC and in the adenocarcinoma (AC) and squamous cell carcinoma (SCC) subtypes compared to NMLT. POSTN expression in CAFs increased with clinical cancer stage, grades (G) of malignancy, and lymph node involvement in NSCLC. Higher POSTN expression in CAFs was an independent prognostic factor for overall survival (OS). LCM confirmed significantly higher POSTN mRNA expression in the stromal cells (CAFs) compared to the lung cancer cells. Conclusions: POSTN produced by CAFs might be crucial for NSCLC progression and can be an independent negative prognostic factor in NSCLC.

A Meta Analysis on Prognostic Value of Patients with Non-Small Cell Lung Cancer

2018 ◽  
Vol 8 (9) ◽  
pp. 1875-1880
Author(s):  
Jiang Rui ◽  
Li Yingping ◽  
Lijun Gu ◽  
Zhiyan Wang ◽  
Jing Zuo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Meta Analysis ◽  
Prognostic Significance ◽  
Small Cell ◽  
Significant Heterogeneity ◽  
Small Cell Lung ◽  
Survival Prognosis ◽  
Nsclc Patients

Nuclear factor kappa B (NF-κB), a key nuclear transcription factor, is associated with prognosis in a variety of human cancers. However, the clinical value of NF-κB in non-small cell lung cancer (NSCLC) is still controversial. Therefore, the aim of this meta-analysis was to obtain an accurate evaluation of the relationship between NF-κB expression and survival prognosis of NSCLC patients based on published articles. PubMed, EMBASE and Web of Science databases were systematically searched for potential articles. A total of 1159 patients from 7 eligible studies comparing prognostic significance of NF-κB expression levels in NSCLC were included in our meta-analysis. I2 statistic and P value were performed to evaluate heterogeneity using Review Manager version 5.3. The results of analysis were presented as hazard ratio (HR) or odds ratios with 95% confidence interval (95% CI). Subgroup analysis based on ethnicity of NSCLC patients was conducted to illustrate the potential discrepancy. Significant heterogeneity was considered at I2 > 50% and P < 0.05, and random-effects model was used. The combined results indicated that higher NF-κB expression was associated with shorter overall survival of NSCLC patients (HR = 2.78, 95% CI = 1.51–5.12, P = 0.001). Moreover, NF-κB expression was closely associated with tumor stage (HR = 0.32, 95% CI = 0.18–0.57, P < 0.0001) and lymph node metastasis (HR = 0.56, 95% CI = 0.38–0.83, P = 0.004). We conclude that NF-κB expression may be a potential unfavorable prognostic marker for NSCLC patients.

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