Transcriptomic and Clinical Profiling Reveals LGALS3 as a Prognostic Oncogene in Pancreatic Cancer

TL;DR

This study shows that LGALS3, a gene encoding Galectin-3, promotes cancer progression and is linked to poor survival in several cancers, including pancreatic cancer.

Contribution

The study identifies LGALS3 as a prognostic oncogene in pancreatic cancer and other malignancies through transcriptomic and clinical profiling.

Findings

LGALS3 deletion affects pathways like mitotic progression and stress responses in cancer cells.

High LGALS3 expression correlates with worse survival in PDAC and other cancers.

LGALS3 knockout in cells confirms its role in cell morphogenesis and proliferation.

Abstract

Background/Objectives: Galectin-3 (Gal-3), encoded by LGALS3, is a β-galactoside-binding lectin involved in diverse tumor-associated processes, including immune modulation, cell cycle regulation, and stress adaptation. Despite its known roles in cancer biology, the full extent of its molecular functions and prognostic relevance across tumor types remains incompletely understood. This study aimed to systematically investigate the transcriptomic impact of LGALS3 deletion and assess its clinical significance in cancer. Methods: We analyzed CRISPR-Cas9 knockout transcriptomic data from the SigCom LINCS database to characterize the consensus gene signature associated with LGALS3 loss using functional enrichment analyses. Pan-cancer survival analyses were conducted using TIMER2.0. Differential Gal-3 protein levels in ductal adenocarcinoma and normal pancreatic tissues were evaluated using the Human Protein Atlas. Finally, functional analyses were performed in pancreatic ductal adenocarcinoma (PDAC). Results: LGALS3 deletion across multiple cancer cell lines led to transcriptomic changes involving mitotic progression, stress responses, and axonal guidance pathways. High LGALS3 expression was significantly associated with worse overall survival in lower-grade glioma, PDAC, uveal melanoma, and kidney renal papillary cell carcinoma. LGALS3 knockout in YAPC cells recapitulated the pan-cancer findings, linking LGALS3 to cell morphogenesis and proliferation. Conclusions: These findings identify Galectin-3 as a key regulator of oncogenic programs and a potential prognostic biomarker in PDAC and other malignancies, with implications for therapeutic targeting.

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