CLPTM1L is known to enhance the survival of malignant cells by engaging endoplasmic reticulum (ER) stress–associated survival mechanisms, whereas TMEM207 disrupts the tumor-suppressive role of WW domain–containing oxidoreductase (WWOX), thereby increasing the vulnerability of cancer cells to apoptosis triggered by ER stress. This study explored whether these two ER stress–linked proteins could function as prognostic biomarkers in oral squamous cell carcinoma (OSCC). Using immunohistochemistry with antibodies against CLPTM1L and TMEM207, we found that 31 of 89 OSCC cases displayed coexpression of both proteins at the invasive front of the tumor. Survival analysis using Kaplan–Meier curves and the log-rank test demonstrated a significant association between dual expression of CLPTM1L and TMEM207 and unfavorable clinical outcomes (P = 0.00252). Their coexpression was also strongly correlated with lymph node involvement (P = 0.000574). Results from both univariate and multivariate models further indicated that this combined expression pattern serves as an independent predictor of poor prognosis. Overall, our findings show that simultaneous immunoreactivity for CLPTM1L and TMEM207 is tightly linked to nodal metastasis and holds prognostic relevance in OSCC.
