The role of WNT10B expression in the prognosis of colorectal cancer: A retrospective study based on TCGA database and clinical data

Abstract

Objective

To evaluate the prognostic value of WNT10B expression in colorectal cancer (CRC) for personalized management.

Methods

We analyzed a TCGA cohort of 644 CRC patients to assess differential expression of WNT family genes between 51 paired tumor-normal samples. Patients were stratified by WNT10B expression to compare overall survival (OS) and progression-free interval (PFI). Prognostic factors were identified via univariate and multivariate Cox regression. For validation, WNT10B protein expression was examined by immunohistochemistry in a separate cohort of 176 CRC patients who underwent surgery at our institution (2016–2020). Kaplan-Meier analysis and univariate Cox regression were used to correlate WNT10B levels with OS and disease-free survival (DFS).

Results

According to TCGA data, WNT10B was upregulated in CRC tumors. Elevated expression was correlated with reduced OS and PFI. Univariate analysis for OS implicated high WNT10B, age >65, lymph node/distant metastasis, positive margin, deep invasion, and abnormal CEA. For PFI, significant factors included high WNT10B, lymph node/distant metastasis, positive margin, deep invasion, and abnormal CEA. Multivariate analysis confirmed high WNT10B, age >65, and a positive margin as independent prognostic factors for OS. High WNT10B expression, distant metastasis, invasion depth and abnormal carcinoembryonic antigen level are the risk factors for independently predicting high tumor recurrence; Postoperative Kaplan-Meier analysis revealed that reduced WNT10B expression was associated with prolonged overall survival (OS), while disease-free survival (DFS) also tended to be longer in the low-expression group, although this trend did not reach statistical significance. Univariate Cox regression identified several factors adversely affecting OS, including elevated WNT10B expression, age ≥65 years, lymph node metastasis, distant metastasis, positive surgical margin, vascular invasion, and perineural invasion. Lymph node metastasis, distant metastasis, vascular invasion, and perineural invasion were also associated with increased recurrence risk. Multivariate analysis confirmed that age ≥65 years, distant metastasis, and vascular invasion were independent predictors of shorter OS. Distant metastasis emerged as an independent risk factor for tumor recurrence.

Conclusion

WNT10B is upregulated in colorectal cancer and correlates with unfavorable outcomes, suggesting its potential utility as a prognostic biomarker and therapeutic target.