Prognostic biomarkers correlated with immune infiltration in non‐small cell lung cancer
Lung cancer is the leading cause of cancer‐related mortality in men and women globally. Non‐small cell lung cancer (NSCLC) is the most prevalent subtype, accounting for 85–90% of all cancers. Although there have been dramatic advances in therapeutic approaches in recent decades, the recurrence and m...
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Format: | Article |
Language: | English |
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Wiley
2023-01-01
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Series: | FEBS Open Bio |
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Online Access: | https://doi.org/10.1002/2211-5463.13501 |
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author | Fei Xu Wen‐qiang Cui Cun Liu Fubin Feng Ruijuan Liu Jingtao Zhang Chang‐gang Sun |
author_facet | Fei Xu Wen‐qiang Cui Cun Liu Fubin Feng Ruijuan Liu Jingtao Zhang Chang‐gang Sun |
author_sort | Fei Xu |
collection | DOAJ |
description | Lung cancer is the leading cause of cancer‐related mortality in men and women globally. Non‐small cell lung cancer (NSCLC) is the most prevalent subtype, accounting for 85–90% of all cancers. Although there have been dramatic advances in therapeutic approaches in recent decades, the recurrence and metastasis rates of NSCLC are as high as 30–40% with the 5‐year overall survival rate being less than 15%. Therefore, it is necessary to explore the pathogenesis of NSCLC at the genetic level and identify prognostic biomarkers and novel therapeutic targets. Here, we aimed to identify mutated genes with high frequencies in Chinese NSCLC patients using next‐generation sequencing and to investigate their relationships with the tumor mutation burden (TMB) and tumor immune microenvironment. A total of 110 NSCLC patients were enrolled to profile the genetic variations. Mutations in EGFR (62.37%), TP53 (61.29%), LRP1B (13.98%), FAT1 (12.90%), KMT2D (11.83%), CREBBP (10.75%), and RB1 (9.68%) were most prevalent. TP53, LRP1B, KMT2D, and CREBBP mutations were all significantly associated with high TMB (P < 0.05 or P < 0.01). The infiltrating levels of immune cells and immune molecules were enriched significantly in the LRP1B mutation group. LRP1B mutations significantly correlated with stimulating and inhibitory immunoregulators. Gene set enrichment analysis revealed that cell cycle, the Notch signaling pathway, the insulin signaling pathway, and the mTOR signaling pathway are related to LRP1B mutations in the immune system. LRP1B mutations may be of clinical importance in enhancing the anti‐tumor immune response and may be a promising biomarker for predicting immunotherapy responsiveness. |
first_indexed | 2024-04-11T01:31:10Z |
format | Article |
id | doaj.art-1bd14c2e745f48f692227503489375b5 |
institution | Directory Open Access Journal |
issn | 2211-5463 |
language | English |
last_indexed | 2024-04-11T01:31:10Z |
publishDate | 2023-01-01 |
publisher | Wiley |
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series | FEBS Open Bio |
spelling | doaj.art-1bd14c2e745f48f692227503489375b52023-01-03T09:41:00ZengWileyFEBS Open Bio2211-54632023-01-01131728810.1002/2211-5463.13501Prognostic biomarkers correlated with immune infiltration in non‐small cell lung cancerFei Xu0Wen‐qiang Cui1Cun Liu2Fubin Feng3Ruijuan Liu4Jingtao Zhang5Chang‐gang Sun6Department of Geriatric Medicine Affiliated Hospital of Shandong University of Traditional Chinese Medicine Jinan ChinaDepartment of Neurology Affiliated Hospital of Shandong University of Traditional Chinese Medicine Jinan ChinaCollege of Traditional Chinese Medicine Shandong University of Traditional Chinese Medicine Jinan ChinaDepartment of Oncology Weifang Traditional Chinese Hospital ChinaDepartment of Oncology Weifang Traditional Chinese Hospital ChinaCollege of Traditional Chinese Medicine Shandong University of Traditional Chinese Medicine Jinan ChinaDepartment of Oncology Weifang Traditional Chinese Hospital ChinaLung cancer is the leading cause of cancer‐related mortality in men and women globally. Non‐small cell lung cancer (NSCLC) is the most prevalent subtype, accounting for 85–90% of all cancers. Although there have been dramatic advances in therapeutic approaches in recent decades, the recurrence and metastasis rates of NSCLC are as high as 30–40% with the 5‐year overall survival rate being less than 15%. Therefore, it is necessary to explore the pathogenesis of NSCLC at the genetic level and identify prognostic biomarkers and novel therapeutic targets. Here, we aimed to identify mutated genes with high frequencies in Chinese NSCLC patients using next‐generation sequencing and to investigate their relationships with the tumor mutation burden (TMB) and tumor immune microenvironment. A total of 110 NSCLC patients were enrolled to profile the genetic variations. Mutations in EGFR (62.37%), TP53 (61.29%), LRP1B (13.98%), FAT1 (12.90%), KMT2D (11.83%), CREBBP (10.75%), and RB1 (9.68%) were most prevalent. TP53, LRP1B, KMT2D, and CREBBP mutations were all significantly associated with high TMB (P < 0.05 or P < 0.01). The infiltrating levels of immune cells and immune molecules were enriched significantly in the LRP1B mutation group. LRP1B mutations significantly correlated with stimulating and inhibitory immunoregulators. Gene set enrichment analysis revealed that cell cycle, the Notch signaling pathway, the insulin signaling pathway, and the mTOR signaling pathway are related to LRP1B mutations in the immune system. LRP1B mutations may be of clinical importance in enhancing the anti‐tumor immune response and may be a promising biomarker for predicting immunotherapy responsiveness.https://doi.org/10.1002/2211-5463.13501lung cancernext‐generation sequencingnon‐small cell lung cancerprognosistumor mutation burdentumor immune microenvironment |
spellingShingle | Fei Xu Wen‐qiang Cui Cun Liu Fubin Feng Ruijuan Liu Jingtao Zhang Chang‐gang Sun Prognostic biomarkers correlated with immune infiltration in non‐small cell lung cancer FEBS Open Bio lung cancer next‐generation sequencing non‐small cell lung cancer prognosis tumor mutation burden tumor immune microenvironment |
title | Prognostic biomarkers correlated with immune infiltration in non‐small cell lung cancer |
title_full | Prognostic biomarkers correlated with immune infiltration in non‐small cell lung cancer |
title_fullStr | Prognostic biomarkers correlated with immune infiltration in non‐small cell lung cancer |
title_full_unstemmed | Prognostic biomarkers correlated with immune infiltration in non‐small cell lung cancer |
title_short | Prognostic biomarkers correlated with immune infiltration in non‐small cell lung cancer |
title_sort | prognostic biomarkers correlated with immune infiltration in non small cell lung cancer |
topic | lung cancer next‐generation sequencing non‐small cell lung cancer prognosis tumor mutation burden tumor immune microenvironment |
url | https://doi.org/10.1002/2211-5463.13501 |
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