Identification and validation of tryptophan-related gene signatures to predict prognosis and immunotherapy response in lung adenocarcinoma reveals a critical role for PTTG1.

Autor:	Wang Z; Anhui Province Key Laboratory of Clinical and Preclinical Research in Respiratory Disease, Molecular Diagnosis Center, Joint Research Center for Regional Diseases of Institute of Health and Medicine (IHM), First Affiliated Hospital of Bengbu Medical University, Bengbu, China.; Research Center of Clinical Laboratory Science, Bengbu Medical University, Bengbu, China., Zhang J; Department of Genetics, School of Life Sciences, Bengbu Medical University, Bengbu, China., Zuo C; Department of Clinical Laboratory, Affiliated Hospital of Guilin Medical University, Guilin, China., Chen H; Research Center of Clinical Laboratory Science, Bengbu Medical University, Bengbu, China., Wang L; Department of Genetics, School of Life Sciences, Bengbu Medical University, Bengbu, China., Xie Y; Department of Clinical Medicine, Bengbu Medical University, Bengbu, China., Ma H; Department of Clinical Medicine, Bengbu Medical University, Bengbu, China., Min S; Anhui Province Key Laboratory of Clinical and Preclinical Research in Respiratory Disease, Molecular Diagnosis Center, Joint Research Center for Regional Diseases of Institute of Health and Medicine (IHM), First Affiliated Hospital of Bengbu Medical University, Bengbu, China., Wang X; Anhui Province Key Laboratory of Clinical and Preclinical Research in Respiratory Disease, Molecular Diagnosis Center, Joint Research Center for Regional Diseases of Institute of Health and Medicine (IHM), First Affiliated Hospital of Bengbu Medical University, Bengbu, China., Lian C; Research Center of Clinical Laboratory Science, Bengbu Medical University, Bengbu, China.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 Jul 31; Vol. 15, pp. 1386427. Date of Electronic Publication: 2024 Jul 31 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1386427
Abstrakt:	Introduction: Tryptophan metabolism is strongly associated with immunosuppression and may influence lung adenocarcinoma prognosis as well as tumor microenvironment alterations. Methods: Sequencing datasets were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database. Two different clusters were identified by consensus clustering, and prognostic models were established based on differentially expressed genes (DEGs) in the two clusters. We investigated differences in mutational landscapes, enrichment pathways, immune cell infiltration, and immunotherapy between high- and low-risk scoring groups. Single-cell sequencing data from Bischoff et al. were used to identify and quantify tryptophan metabolism, and model genes were comprehensively analyzed. Finally, PTTG1 was analyzed at the pan-cancer level by the pan-TCGA cohort. Results: Risk score was defined as an independent prognostic factor for lung adenocarcinoma and was effective in predicting immunotherapy response in patients with lung adenocarcinoma. PTTG1 is one of the key genes, and knockdown of PTTG1 in vitro decreases lung adenocarcinoma cell proliferation and migration and promotes apoptosis and down-regulation of tryptophan metabolism regulators in lung adenocarcinoma cells. Discussion: Our study revealed the pattern and molecular features of tryptophan metabolism in lung adenocarcinoma patients, established a model of tryptophan metabolism-associated lung adenocarcinoma prognosis, and explored the roles of PTTG1 in lung adenocarcinoma progression, EMT process, and tryptophan metabolism. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Wang, Zhang, Zuo, Chen, Wang, Xie, Ma, Min, Wang and Lian.)
Databáze:	MEDLINE
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