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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Main Authors: Fei Xu, Wen‐qiang Cui, Cun Liu, Fubin Feng, Ruijuan Liu, Jingtao Zhang, Chang‐gang Sun
Format: Article
Language:English
Published: Wiley 2023-01-01
Series:FEBS Open Bio
Subjects:
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.
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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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