Affiliation:
1. Department of Thoracic Surgery, Peking University Shenzhen Hospital, Shenzhen, 518036, China
Abstract
Aims:
The study aimed to explore the effect of metabolism on lung cancer.
Background:
The tumor microenvironment is largely influenced by metabolism, tightly involved in
tumor progression.
Objective:
We try to investigate the effect of tumor metabolism terms on non-small cell lung cancer
(NSCLC) prognosis, drug and immunotherapy sensitivity, as well as its underlying mechanisms.
Methods:
All the data was obtained from The Cancer Genome Atlas and Gene Expression Omnibus
databases. R software was used to perform all statistical analyses and plots.
Results:
This study conducted 21 metabolism statuses in NSCLC to identify their underlying roles.
We found that alpha-linolenic acid metabolism, sphingolipid metabolism, glycerophospholipid metabolism,
fatty acid degradation, linoleic acid metabolism, primary bile acid biosynthesis, and fatty acid
metabolism were protective factors for NSCLC. Next, we constructed a prognosis model based on
primary bile acid biosynthesis, glycerophospholipid, and sphingolipid metabolism. Results in the present
study showed that our model could effectively predict patients' prognosis in both training and validation
cohorts. A clinical correlation revealed that patients at high-risk exhibited more progressive
clinical characteristics. Biological enrichment indicated that MYC targets, E2F targets, mTORC1 signaling,
G2/M checkpoint, and epithelial-mesenchymal transition were activated in the high-risk group.
Immune relation analysis showed that risk score positively correlated with Th2 cells, yet a negative
correlation with CD56 bright NK, Th17, mast and CD8+ T cells. Moreover, our model was related to
NSCLC patients' sensitivity to immunotherapy and chemotherapy. Ultimately, eight characteristic
genes were identified to distinguish the patients' risk group in the real application.
Conclusions:
The model we developed is a useful tool to predict NSCLC patients' prognosis and is
associated with the sensitivity of immunotherapy and chemotherapy. Meanwhile, our results can guide
the following metabolism-related studies in NSCLC.
Publisher
Bentham Science Publishers Ltd.
Subject
Cancer Research,Drug Discovery,Pharmacology,Oncology