PELP1 expression is associated with disease progression in inflammation-driven oral cancer.

Authors

Vedhashree Somashankar, Roshni Saravanan, Anugraha Mathavan, Abirami Seetharaman, Rachael Jahander Khodabux, Harikrishnan Thamizh Chelvan, Suresh Kumar Rayala, Ganesh Venkatraman

Published in

Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico. Aug 16, 2026. Epub Aug 16, 2026.

Abstract

Chronic inflammation is an important contributor to the development of oral cancer, particularly in Oral Potentially Malignant Disorders (OPMDs) progressing to Oral Squamous Cell Carcinoma (OSCC). PELP1 is an inflammation-responsive nuclear coregulator identified in multiple cancers; however, its role in oral cancer remains unclear. This study evaluates the expression of PELP1 and determines its clinical significance in inflammation-associated oral tumorigenesis.
PELP1 transcript levels were examined in the TCGA-HNSC dataset using different online tools. Immune infiltration analysis using TIMER and Kaplan-Meier survival analysis plots was also performed. Protein expression was validated by immunohistochemistry (IHC) in human normal oral mucosa, OPMDs, and OSCC tissues and in chemically induced murine OSMF models. Functional validation was performed by shRNA-mediated PELP1 knockdown in SCC131 cells, followed by western blot analysis of Cyclin B1 and NF-κB signaling.
PELP1 expression was significantly upregulated in TCGA-HNSC tumors compared to normal tissues (p < 0.05) and was associated with advanced stage, higher grade, and nodal metastasis (p < 0.05). A positive correlation and a significant association between PELP1 expression and the abundance of immune cell infiltrates were observed (p < 0.05). In addition, high PELP1 expression was associated with markers of oral epithelial transformation (p < 0.05). Survival analysis showed a trend toward reduced overall survival (p = 0.24). IHC analysis showed a stepwise increase in nuclear PELP1 expression from normal mucosa to OPMDs; and OSCC (p < 0.05); along with elevated expression in fibrotic murine models (p < 0.05) compared to saline-treated control models. Functional validation demonstrated that PELP1 knockdown reduced Cyclin B1 expression, reduced total NF-κB p65 protein levels, and suppressed NF-κB signalling in SCC131 cells.
PELP1 is significantly upregulated during oral cancer development and correlates with adverse clinicopathological features, supporting its potential role as a biomarker associated with inflammation-driven oral cancer progression.

PMID:
42604464
Bibliographic data and abstract were imported from PubMed on 17 Aug 2026.

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