Identification and Validation of Tryptophan-related Gene Signatures to Predict Prognosis and Immunotherapy Response in Lung Adenocarcinoma Reveals a Critical Role for PTTG1

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2024 Aug 15

PMID 39144144

Authors

Ziqiang Wang

Jing Zhang

Chao Zuo

Huili Chen

Luyao Wang

Yiluo Xie

Hongyu Ma

Shengping Min

Xiaojing Wang

Chaoqun Lian

Affiliations

Soon will be listed here.

Abstract

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 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.

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