Multi-omics analysis identifies PTTG1 as a prognostic biomarker associated with immunotherapy and chemotherapy resistance

Handong Wei ¹, Yaxin Ma ¹, Shuxing Chen ¹

⁰Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education, Center for Translational Medicine and School of Preclinical Medicine, Guangxi Medical University, Nanning, Guangxi, China.

Bmc Cancer +

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October 25, 2024

View abstract on PubMed

Summary

Pituitary tumor-transforming gene 1 (PTTG1) is overexpressed in most cancers, correlating with poor prognosis and immunotherapy resistance. Targeting PTTG1 may improve cancer treatment outcomes and overcome drug resistance.

Area Of Science

Oncology
Molecular Biology
Cancer Genomics

Background

Pituitary tumor-transforming gene 1 (PTTG1) plays a role in tumor development.
The prognostic significance of PTTG1 in pan-cancer, including its impact on immunotherapy response and drug sensitivity, requires comprehensive investigation.

Purpose Of The Study

To determine the role of PTTG1 in tumor prognosis, immunotherapy response, and medication sensitivity across 33 human malignancies.
To explore PTTG1's association with the tumor immune microenvironment and its potential as a therapeutic target.

Main Methods

Utilized TCGA cohort data via TIMER, GEPIA, Human Protein Atlas, TISCH2, and cBioportal to analyze PTTG1 expression, prognosis, and genetic alterations.
Investigated PTTG1's correlation with tumor immunity, microenvironment, immunotherapy response, and drug sensitivity using GSCA, TIDE, and CellMiner CDB.
Employed molecular docking and siRNA-mediated knockdown to validate PTTG1's role in chemoresistance, particularly to paclitaxel.

Main Results

PTTG1 is overexpressed in most tumors, linked to poor survival and involvement in cell cycle and DNA replication.
Elevated PTTG1 expression correlates with increased immune cell infiltration, tumor microenvironment modulation, and resistance to immunotherapy, potentially via T cell exhaustion.
PTTG1 expression is significantly associated with sensitivity to various anticancer drugs, and its suppression reduces cell proliferation and migration, indicating a role in paclitaxel resistance.

Conclusions

PTTG1 serves as a potential biomarker for cancer diagnosis, prognosis, and chemosensitivity.
Increased PTTG1 expression is associated with treatment resistance, possibly through cytotoxic T lymphocyte dysfunction and T cell exhaustion.
PTTG1, expressed on regulatory and proliferating T cells, represents a potential therapeutic target for overcoming immunotherapy resistance.

Keywords:

Drug sensitivity Immunotherapy PTTG1 Pan-cancer Tumor immunity