Prognostic significance of RKIP, TGM2, and CMTM4 expression in oral squamous cell carcinoma - Clinical Trial/Experimental Study

Q: What is the study’s primary objective regarding RKIP, TGM2, and CMTM4?

To determine expression patterns of RKIP, TGM2, and CMTM4 in OSCC and normal tissues, analyze their associations with clinicopathological parameters, and assess their prognostic relevance.

Q: How were protein expression levels measured in the study?

Protein expression was detected using immunohistochemistry (IHC) on paraffin-embedded tissue samples.

Q: Which markers were suggested to predict prognosis in OSCC patients?

Kaplan–Meier survival analysis suggested positive TGM2 and CMTM4 expression may predict poor prognosis, and multivariate Cox analysis indicated TGM2 could be an independent prognostic factor.

Sep 21, 2026

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Expression levels of RKIP, TGM2, and CMTM4 were measured in oral squamous cell carcinoma (OSCC) and adjacent normal tissues to clarify clinical associations and prognostic value. Seventy paired samples were processed for paraffin embedding, followed by immunohistochemistry to detect protein expression. Statistical analysis used chi-squared tests for expression-feature links, Kaplan–Meier survival with log-rank comparisons, and multivariate Cox regression to evaluate independent prognostic effects. Findings indicate TGM2 and CMTM4 may signal poor outcomes.

LanguageEnglish

CategoryHealthcare

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Abstract

Introduction

Materials and methods

® Clinical Trial/Experimental Study Prognostic significance of RKIP, TGM2, and CMTM4 expression in oral squamous cell carcinoma Tianyu Luoa , Tao Xu, MDb ,* , Yurong Ou, MDc , Hongfei Ci, MDc , Junhui Suna | Abstract
Background: The expression of RKIP, TGM2, and CMTM4 in oral squamous cell carcinoma (OSCC) and normal oral tissues was detected and their correlations were analyzed. The relationships between RKIP, TGM2, and CMTM4 and the clinicopathological parameters and prognosis of patients were analyzed.
Methods: Seventy cancerous and adjacent normal tissue samples were selected, recorded in the pathology department, and embedded in paraffin. Protein expression was detected by immunohistochemistry. Statistical software (SPSS 25.0, IBM Corporation) was used for the statistical analysis. The chi-squared (χ2) test was used to analyze the expression of RKIP, TGM2, and CMTM4 proteins and their clinicopathological features. Differences in RKIP, TGM2, and CMTM4 protein levels between OSCC and normal tissues were compared using a χ2 test. Survival analysis was performed using the Kaplan–Meier method, and differences between survival curves were determined using the log-rank test. The effects of RKIP, TGM2, and CMTM4 expression on patient prognosis were analyzed using a multivariate Cox proportional hazards regression model. P < .05 was considered statistically significant.
Results: The expression level of RKIP correlated with age and clinical stage (P < .05) . TGM2 was associated with clinical stage and lymph node metastasis (P < .05) . The expression of CMTM4 increased with a decrease in cancer differentiation. Kaplan–Meier survival analysis suggested that the positive expression of TGM2 and CMTM4 may predict poor prognosis in patients with OSCC. The multivariate Cox proportional hazards regression model suggested that TGM2 could be an independent prognostic factor for patients with OSCC.
Conclusion: Combined expression of TGM2 and CMTM4 can be used as an indicator to evaluate the risk of metastasis and prognosis of OSCC.
Abbreviations: CKLFSF = chemokine like factor superfamily, CSC = cancer stem cell, EMT = epithelial-mesenchymal transition, HNSCC = head and neck squamous cell carcinoma, IHC = immunohistochemistry, OSCC = oral squamous cell carcinoma, PDL1 = programmed death‐ligand 1, PEBP = phosphatidylethanolamine-binding protein, RKIP = Raf kinase inhibitor protein, TGM2 = transglutaminase 2, TNM = tumor-node-metastasis, TSCC = tongue squamous cell carcinoma. | | --- | | Keywords: CMTM4 , immunohistochemistry, OSCC, prognosis, RKIP, TGM2 | 1. Introduction Oral squamous cell carcinoma (OSCC) is the most common typeof oral cancer in the world.[1] its occurrence and development are affected by both endogenous and exogenous factors. Owing to the rich blood supply in the oral and maxillofacial regions, OSCC is prone to invasion and metastasis, and its 5-year survival rate is as low as 50% .[2] The Raf kinase inhibitor protein (RKIP) is a tumor suppressor in the PEBP family. It mainly plays a role by binding to Raf-1 to affect the MEK/ERK signaling pathway and regulate the G protein-coupled receptor (GPCR) and NF-κB signaling pathways.[3–5] transglutaminase2 (TGM2), a highly complex calcium-dependent multifunctional protein, is expressed to varying degrees in almost all body cells. It plays an essential role in the epithelial-mesenchymal transition, cell metastasis, apoptosis, and differentiation of cancer stem cells through noncovalent interactions with various cellular proteins.[6,7] CMTM4 is a member of the CMTM protein family. The original name of the CMTM family is the chemokine-like factor superfamily (CKLFSF), which was named CMTM l-8 by the International Committee on Human Gene Nomenclature (2005) .[8] CMTM The authors have no funding and conflicts of interest to disclose. The datasets generated during and/or analyzed during the current study are available from the corresponding author on re

FAQs

What is the study’s primary objective regarding RKIP, TGM2, and CMTM4?

To determine expression patterns of RKIP, TGM2, and CMTM4 in OSCC and normal tissues, analyze their associations with clinicopathological parameters, and assess their prognostic relevance.

How were protein expression levels measured in the study?

Protein expression was detected using immunohistochemistry (IHC) on paraffin-embedded tissue samples.

Which markers were suggested to predict prognosis in OSCC patients?

Kaplan–Meier survival analysis suggested positive TGM2 and CMTM4 expression may predict poor prognosis, and multivariate Cox analysis indicated TGM2 could be an independent prognostic factor.

Sep 21, 2026

Upload by Himbo