Seven Autophagy-Related Genes are Associated with the Tumor Immune Microenvironment in Predicting Survival Risk of Non-Small Cell Lung Cancer

Abstract Background: Non-small cell lung cancer (NSCLC) ranks first among global cancer-related deaths. Despite the emergence of various immunological and targeted therapies, immune tolerance remains a barrier to treatment. Methods: It has been found that this obstacle can be overcome by targeting autophagy-related genes (ATGs). ATGs were screened by coexpression analysis and the genes related to the prognosis of lung cancer were screened using Kaplan–Meier (K-M) survival analysis, univariate Cox regression, and multivariate Cox regression. The prognostic risk model of ATGs was constructed and verified using K-M survival analysis and receiver operating characteristic (ROC) curve analysis. Results: The prognostic risk model of ATGs was constructed. Gene set enrichment analysis (GSEA) showed that the function and pathway of ATG enrichment were closely related to immune cell function. CIBERSORT, LM22 matrix, and Pearson correlation analysis showed that risk signals were significantly correlated with immune cell infiltration and immune checkpoint genes. Conclusions: We identified and independently verified the ATG (AL691432.2, MMP2-AS1, AC124067.2, CRNDE, ABALON, AL161431.1, NKILA) in NSCLC patients and found that immune regulation in the tumor microenvironment is closely related to this gene.

Download Full-text

The Prognostic Value of a Glycolysis -Related lncRNA Signature in Non-Small Cell Lung Cancer

10.21203/rs.3.rs-819919/v1 ◽

2021 ◽

Author(s):

Yongquan Dong ◽

Wenping Xia ◽

Hefei Zhu ◽

Feijie Lu ◽

Lijuan Wei ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Cox Regression ◽

Risk Group ◽

Small Cell ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Small Cell Lung ◽

Cox Regression Analysis

Abstract Backgroud: Long non-coding RNA(lncRNA) is a new modulatory factor for glycolysis, which affect the development and progression of varities of cancers. However, poor attention has been drawn to the role of glycolysis-related lncRNAs in Non-small cell lung cancer(NSCLC) . Methods: The RNA sequencing(RNA-seq) data of NSCLC patients was downloaded from The Cancer Genome Atlas(TCGA) database. Glycolysis-related genes were identified using Gene Set Enrichment Analysis(GSEA). Cox regression analysis was used to construct the glycolysis-related signature. GSEA analysis was used for function assessment. Results: Firstly, a signature consisting of 8 glycolysis-related lncRNAs(AC090559.1, AC099850.3,AL365181.3, AL049555.1, AC024075.3, LINC01843, ATP13A4-AS1 and LINC01133)were estimated. Moreover, on the basis of this signature, we found that overall survival(OS) in high-risk group was markedly lower than that in low-risk group, and the prognostic prediction accuracy was further verified by Multi-parameter ROC curve analysis. Lastly, the 8 glycolysis-related lncRNAs were found to be closely associated with many cancer-related pathways. Conclusion: The 8 glycolysis-related lncRNAs could be promising prognostic and potential therapeutic targets for NSCLC.

Download Full-text

Biomarkers and Gene Signatures to Predict Durable Response to Pembrolizumab in Non-Small Cell Lung Cancer

Cancers ◽

10.3390/cancers13153828 ◽

2021 ◽

Vol 13 (15) ◽

pp. 3828

Author(s):

Anello Marcello Poma ◽

Rossella Bruno ◽

Iacopo Pietrini ◽

Greta Alì ◽

Giulia Pasquini ◽

...

Keyword(s):

Lung Cancer ◽

T Cells ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Immune Cell ◽

Small Cell ◽

Small Cell Lung ◽

First Line ◽

Durable Response ◽

Nsclc Patients

Pembrolizumab has been approved as first-line treatment for advanced Non-small cell lung cancer (NSCLC) patients with tumors expressing PD-L1 and in the absence of other targetable alterations. However, not all patients that meet these criteria have a durable benefit. In this monocentric study, we aimed at refining the selection of patients based on the expression of immune genes. Forty-six consecutive advanced NSCLC patients treated with pembrolizumab in first-line setting were enrolled. The expression levels of 770 genes involved in the regulation of the immune system was analysed by the nanoString system. PD-L1 expression was evaluated by immunohistochemistry. Patients with durable clinical benefit had a greater infiltration of cytotoxic cells, exhausted CD8, B-cells, CD45, T-cells, CD8 T-cells and NK cells. Immune cell scores such as CD8 T-cell and NK cell were good predictors of durable response with an AUC of 0.82. Among the immune cell markers, XCL1/2 showed the better performance in predicting durable benefit to pembrolizumab, with an AUC of 0.85. Additionally, CD8A, CD8B and EOMES showed a high specificity (>0.86) in identifying patients with a good response to treatment. In the same series, PD-L1 expression levels had an AUC of 0.61. The characterization of tumor microenvironment, even with the use of single markers, can improve patients’ selection for pembrolizumab treatment.

Download Full-text

P1.04-03 Suppressive Immune Cell Profiling in Patients with Non-Small Cell Lung Cancer

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2018.08.718 ◽

2018 ◽

Vol 13 (10) ◽

pp. S526

Author(s):

J. Koh ◽

K.Y. Lee ◽

B. Kim ◽

M.S. Kim ◽

H.J. Cho ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Immune Cell ◽

Small Cell ◽

Small Cell Lung

Download Full-text

Overall Survival Analysis and Characterization of an EGFR Mutated Non-Small Cell Lung Cancer (NSCLC) Population

Archivos de Bronconeumología (English Edition) ◽

10.1016/j.arbr.2017.07.016 ◽

2018 ◽

Vol 54 (1) ◽

pp. 10-17

Author(s):

Filipa Aguiar ◽

Gabriela Fernandes ◽

Henrique Queiroga ◽

José Carlos Machado ◽

Luís Cirnes ◽

...

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Survival Analysis ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Small Cell Lung ◽

Egfr Mutated ◽

Overall Survival Analysis

Download Full-text

P14.25 Immune Cell Profiling of Hyperprogressive Disease in Patients with Non-Small Cell Lung Cancer Treated with Anti-PD-1/PD-L1 Antibodies

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2021.01.531 ◽

2021 ◽

Vol 16 (3) ◽

pp. S340

Author(s):

K.H. Kim ◽

J.Y. Hur ◽

B.M. Ku ◽

J. Koh ◽

M. Ahn ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Immune Cell ◽

Small Cell ◽

Small Cell Lung ◽

Hyperprogressive Disease

Download Full-text

Efficacy and toxicity hypofractionated radiotherapy for centrally located non-small cell lung cancer

Journal of Radiotherapy in Practice ◽

10.1017/s1460396921000376 ◽

2021 ◽

pp. 1-4

Author(s):

Tanzeel Janjua ◽

Fei Sun ◽

Katy Clarke ◽

Pete Dickinson ◽

Kevin Franks ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Cox Regression ◽

Early Stage ◽

Performance Status ◽

Small Cell ◽

Small Cell Lung ◽

Early Stage Lung Cancer ◽

Cox Regression Analysis

Abstract Aim: Centrally located early-stage non-small cell lung cancer in patients who are unfit for surgery are treated with fractionated radiotherapy. We present the outcomes of a moderately hypofractionated accelerated dose regimen of 50 Gy in 15 fractions from a single centre in the UK. Materials and methods: Electronic case notes and radiotherapy records of lung cancer patients treated between January 2014 and December 2016 were retrospectively reviewed. Adult Comorbidity Evaluation-27 score was used to evaluate comorbidities. Mean lung doses and percentage of lung receiving more than 20 Gy were calculated for all patients. Survival outcomes were estimated using Kaplan–Meier curves. Results: Fifty-three patients were included in the study; the median follow-up was 20.2 months. 87% of patients had stage I disease. There was no 30-day post-treatment mortality. Ninety-day mortality rate after radiotherapy was 3.8%. Grade 2 pneumonitis was seen in five patients while no grade 3 or 4 pneumonitis was observed. The median progression-free survival (PFS) and overall survival (OS) were 18.5 months and 28.2 months, respectively. The estimated 1 and 2 years PFS were 62.3% and 41.3%, respectively, and OS were 77.4% and 56.6%, respectively. Worsening performance status was associated with worse survival on cox regression analysis. Disease relapsed in 36% of patients. 7.5% of patients with relapsed disease had infield recurrence. Findings: 50 Gy in 15 fractions radiotherapy for central early-stage lung cancer is a feasible choice that requires further randomised trials.

Download Full-text

Prognostic factors for survival in advanced non-small-cell lung cancer: univariate and multivariate analyses including recursive partitioning and amalgamation algorithms in 1,052 patients. The European Lung Cancer Working Party.

Journal of Clinical Oncology ◽

10.1200/jco.1995.13.5.1221 ◽

1995 ◽

Vol 13 (5) ◽

pp. 1221-1230 ◽

Cited By ~ 268

Author(s):

M Paesmans ◽

J P Sculier ◽

P Libert ◽

G Bureau ◽

G Dabouis ◽

...

Keyword(s):

Lung Cancer ◽

Prognostic Factors ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Cox Regression ◽

Recursive Partitioning ◽

Working Party ◽

Small Cell ◽

Small Cell Lung

PURPOSE This study attempted to determine the prognostic value for survival of various pretreatment characteristics in patients with nonresectable non-small-cell lung cancer in the context of more than 10 years of experience of a European Cooperative Group. PATIENTS AND METHODS We included in the analysis all eligible patients (N = 1,052) with advanced non-small-cell lung cancer registered onto one of seven trials conducted by the European Lung Cancer Working Party (ELCWP) during one decade. The patients were treated by chemotherapy regimens based on platinum derivatives. We prospectively collected 23 variables and analyzed them by univariate and multivariate methods. RESULTS The global estimated median survival time was 29 weeks, with a 95% confidence interval of 27 to 30 weeks. After univariate analysis, we applied two multivariate statistical techniques. In a Cox regression model, the selected explanatory variables were disease extent, Karnofsky performance status, WBC and neutrophil counts, metastatic involvement of skin, serum calcium level, age, and sex. These results were confirmed by application of recursive partitioning and amalgamation algorithms (RECPAM), which led to classification of the patients into four homogeneous subgroups. CONCLUSION We confirmed by our analysis the role of well-known independent prognostic factors for survival, but also identified the effect of the neutrophil count, rarely studied, with the use of two methods: a classical Cox regression model and a RECPAM analysis. The classification of patients into the four subgroups we obtained needs to be validated in other series.

Download Full-text

Evaluation of sensitivity and specificity of CanPatrol™ technology for detection of circulating tumor cells in patients with non-small cell lung cancer

BMC Pulmonary Medicine ◽

10.1186/s12890-020-01314-4 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Jingyao Li ◽

Yi Liao ◽

Yaling Ran ◽

Guiyu Wang ◽

Wei Wu ◽

...

Keyword(s):

Lung Cancer ◽

Survival Analysis ◽

Small Cell Lung Cancer ◽

Tumor Cells ◽

Sensitivity And Specificity ◽

Cell Lung Cancer ◽

Small Cell ◽

Small Cell Lung ◽

Kaplan Meier ◽

Nsclc Patients

Abstract Background The early diagnosis of non-small cell lung cancer is of great significance to the prognosis of patients. However, traditional histopathology and imaging screening have certain limitations. Therefore, new diagnostical methods are urgently needed for the current clinical diagnosis. In this study we evaluated the sensitivity and specificity of CanPatrol™ technology for the detection of circulating tumor cells in patients with non-small cell lung cancer (NSCLC). Methods CTCs in the peripheral blood of 98 patients with NSCLC and 38 patients with benign pulmonary diseases were collected by the latest typing of CanPatrol™ detection technology. A 3-year follow-up was performed to observe their recurrence and metastasis. Kruskal-Wallis test was used to compare multiple groups of data, Mann-Whitney U test was used to compare data between the two groups, and ROC curve analysis was used to obtain the critical value. The COX risk regression and Kaplan-Meier survival analysis were performed in the 63 NSCLC patients who were effectively followed up. Results The epithelial, epithelial-mesenchymal, and total CTCs were significantly higher in NSCLC patients than that in patients with benign lung disease (P < 0.001). The mesenchymal CTCs of NSCLC patients was slightly higher than that of benign lung diseases (P = 0.013). The AUC of the ROC curve of the total CTCs was 0.837 (95% CI: 0.76-0.914), and the cut-off value corresponding to the most approximate index was 0.5 CTCs/5 ml, at which point the sensitivity was 81.6% and the specificity was 86.8%. COX regression analysis revealed that the clinical stage was correlated with patient survival (P = 0.006), while gender, age, and smoking were not (P > 0.05). After excluding the confounders of staging, surgery, and chemotherapy, Kaplan-Meier survival analysis showed that patients in stage IIIA with CTCs ≥0.5 had significantly lower DFS than those with CTCs < 0.5 (P = 0.022). Conclusions CTC positive can well predict the recurrence of NSCLC patients. CanPatrol™ technology has good sensitivity and specificity in detecting CTCs in peripheral blood of NSCLC patients and has a certain value for clinical prognosis evaluation.

Download Full-text