Overexpression of PSAT1 is Correlated with Poor Prognosis and Immune Infiltration in Non-Small Cell Lung Cancer

Hongmu Li; Chun Wu; Wuguang Chang; Leqi Zhong; Wuyou Gao; Mingyue Zeng; Zhesheng Wen; Shijuan Mai; Youfang Chen

doi:10.31083/j.fbl2810243

Overexpression of PSAT1 is Correlated with Poor Prognosis and Immune Infiltration in Non-Small Cell Lung Cancer

Front Biosci (Landmark Ed). 2023 Oct 19;28(10):243. doi: 10.31083/j.fbl2810243.

Authors

Hongmu Li^{1

2}, Chun Wu², Wuguang Chang^{1

2}, Leqi Zhong^{1

2}, Wuyou Gao^{1

2}, Mingyue Zeng^{1

2}, Zhesheng Wen^{1

2}, Shijuan Mai², Youfang Chen^{1

2}

Affiliations

¹ Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, 510060 Guangzhou, Guangdong, China.
² State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, 510060 Guangzhou, Guangdong, China.

PMID: 37919070
DOI: 10.31083/j.fbl2810243

Abstract

Purpose: Current evidence suggests that phosphoserine aminotransferase 1 (PSAT1) is overexpressed in various tumors. Herein, we investigate the significance of PSAT1 in non-small cell lung cancer (NSCLC) and its correlation with immune infiltration.

Methods: The expression profile of PSAT1 in NSCLC patients and related clinical information was obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA-NSCLC) databases. In silico and experimental validation were conducted to assess the role of PSAT1 in NSCLC. Gene set enrichment analysis (GSEA) was performed to investigate the disparities in biological functions between groups with high and low PSAT1 expression. Additionally, the biological characteristics and immune cell infiltration were compared between these two groups. We also assessed whether PSAT1 expression could predict the sensitivity of NSCLC patients to immunotherapy using the immunophenotype score (IPS) and an anti-PD-L1 immunotherapy cohort (IMvig-or210). Furthermore, the difference in drug sensitivity between PSAT1-high and PSAT1-low expression cell lines was investigated.

Results: Analysis of transcriptional expression profiles using TCGA data revealed overexpression of PSAT1 in NSCLC tissues correlated with poor overall survival (OS). GSEA results showed enrichment of DNA recombination and repair, nucleotide biosynthesis, and the P53 signaling pathway in the PSAT1-high group. Experimental validation demonstrated that the knockdown of PSAT1 suppressed cell proliferation, migration, and invasion of NSCLC. Immune cell infiltration analysis revealed an immune-activated tumor microenvironment in the PSAT1-low group. It was also observed that PSAT1-low cell lines were more likely to benefit from immunotherapy and several chemotherapy drugs.

Conclusions: PSAT1 has enormous potential for applications in the prediction of NSCLC patient outcomes and provides the foothold for more precise individualized treatment of this patient population.

Keywords: chemotherapy; immune infiltration; immunotherapy; non-small-cell lung cancer; prognostic biomarker.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Non-Small-Cell Lung* / genetics
Cell Line
Cell Proliferation / genetics
Humans
Immunotherapy
Lung Neoplasms* / genetics
Tumor Microenvironment / genetics

Substances

PSAT1 protein, human