Prognostic significance of GPR132 in papillary thyroid carcinoma: insights from integrated machine learning and its role in regulating TPC-1 cell growth

TL;DR

This study identifies GPR132 as a potential prognostic marker and tumor suppressor in papillary thyroid carcinoma through machine learning and cell experiments.

Contribution

The study introduces GPR132 as a novel prognostic gene for papillary thyroid carcinoma and demonstrates its tumor-suppressive role in cell cycle and apoptosis.

Findings

GPR132 overexpression inhibits TPC-1 cell proliferation and migration.

GPR132 induces G1 phase cell cycle arrest and enhances apoptosis in thyroid cancer cells.

GPR132 is linked to M1-like macrophage gene modules associated with better PTC prognosis.

Abstract

This study utilizes machine learning and bioinformatics methods to analyze data identifying GPR132 as a reliable potential prognostic gene for papillary thyroid carcinoma (PTC).The experiments elucidated potential role of GPR132 in inhibiting tumor growth in PTC by regulating the cell cycle and apoptotic mechanisms. This research provides significant insights for future personalized therapeutic strategies aimed at targeting PTC.

The study analyzed the GSE191288 RNA-seq dataset, which included six thyroid cancer tumor samples and one adjacent normal tissue sample, to identify genes associated with tumor-associated macrophages (TAMs). After conducting a thorough enrichment analysis, we used the CellChat tool to investigate the signaling pathways.Pseudotemporal analysis elucidated the differentiation status of TAMs, and weighted gene co-expression network analysis(WGCNA) identified M1-like TAM-related genes within the M1 macrophage module. Integration with the GEO database revealed that GPR132 is a key prognostic gene. The effects of GPR132 overexpression on the proliferation, migration, apoptosis, and cell cycle progression of thyroid papillary carcinoma (TPC-1) cells were evaluated through cell-based experiments.

Single-cell sequencing revealed 20 distinct cell clusters, categorized as epithelial, stromal, or immune cells, with a focus on TAMs.Enrichment analysis associated TAM-expressed genes with immune response regulation. Pseudotime analysis identified TAMs differentiation states, while WGCNA linked a low abundance of M1 macrophages to favorable PTC prognosis. Integration with the GEO database confirmed GPR132 as a key prognostic gene. Cellular experiments showed that GPR132 overexpression markedly inhibited TPC-1 cell proliferation and migration, likely through G1 phase cell cycle arrest and enhanced apoptosis. Flow cytometry confirmed elevated early and total apoptosis rates in GPR132-overexpressing cells.

GPR132 was identified as a critical prognostic gene for PTC, with evidence suggesting its role in tumor suppression via cell cycle modulation and apoptosis induction.

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