Tissue Cadherin 17 (CDH17): An Important Prognostic Determinant of Colorectal Cancer Using Digital Image Analysis

Abstract

Background: Colorectal cancer (CRC) is a commonly diagnosed malignancy with significant mortality rates worldwide. The identification of robust prognostic biomarkers for prediction of survival outcomes and recurrence can aid disease management and improve patients' quality of living.

Aim: This study aimed to investigate the prognostic value of cadherin 17 (CDH17) tissue expression in CRC patients by utilizing a standardized automated immunohistochemistry (IHC) platform integrated with a digitalized scoring system.

Methods and results: IHC was conducted to assess CDH17 expression on tumor tissues obtained from 150 retrospective CRC cases. A computer-assisted imaging analysis was performed to quantify CDH17 tissue expression using an IHC scoring algorithm known as the Membrane (M) Score. The relationship between CDH17 M Score and clinicopathological factors such as TNM staging, distant metastasis, and recurrence status was analyzed. The prognostic value of CDH17 M Score was determined by Kaplan-Meier curves and Cox regression analysis for overall survival (OS) and recurrence-free survival (RFS). Comparison of M Score and pathologist visual scoring was made to assess the validity of software-derived IHC scoring. CDH17 expression, as measured by M Score, was found to be significantly increased in tumor tissues compared to adjacent normal tissues, and its expression is associated with advanced staging and distant metastasis (normal vs. tumor, p = 0.0011; Stages IV vs. I-III, p < 0.0162; with vs. without metastasis, p = 0.0026; Mann-Whitney U test). Prognostic analysis revealed that high CDH17 M Score was associated with poor OS and RFS (OS, p = 0.0118; RFS, p = 0.0021; log-rank test). Furthermore, multivariate Cox regression analysis identified that CDH17 M Score was an independent prognostic predictor for OS (HR = 2.296, 95% CI = 1.154-4.968, p = 0.0240) and RFS (HR = 2.489, 95% CI = 1.062-6.494, p = 0.0447).

Conclusion: Increased CDH17 M Score was associated with advanced tumor staging and poor survival outcomes using an automated IHC system integrated with a digital image analysis software, highlighting CDH17 could serve as an independent prognostic marker for CRC patients.

Keywords: automated immunohistochemistry; cadherin 17; colorectal cancer; prognosis.

FIGURE 1

Retrospective analysis of 150 colorectal cancer (CRC) cases. (A) Comparison of M Scores between paired adjacent normal tissue and CRC tumor tissue. (B) Comparison of M Scores between tumor tissue from early‐stage (I and II) and late‐stage (III and IV) CRC. (C) Comparison of M Scores among tumor tissue from Stages from I to IV of CRC. (D) Comparison of M Scores between tumor tissue from metastatic and nonmetastatic CRC.

FIGURE 2

Kaplan–Meier survival analysis of the prognostic impact of M Score on overall survival. (A) Overall survival curve of patients by M Score categories. (B) Overall survival curve of patients categorized as high M Score and low M Score. (C) Overall survival curve of patients with early‐stage CRC categorized by high and low M Score. (D) Overall survival curve of patients with late‐stage CRC categorized by high and low M Score. The cut‐off value for high M Score = 33.15.

FIGURE 3

Kaplan–Meier survival analysis of the prognostic impact of M Score on recurrence‐free survival (RFS). (A) Comparison of M Scores between tumor tissue from CRC patients with and without recurrence. (B) Overall survival curve of patients categorized by early (< 2 years) and late recurrence (≥ 2 years). (C) RFS curve of patients by M Score categories. (D) RFS curve of patients categorized as high M Score and low M Score. (E) RFS curve of patients with early‐stage CRC categorized by high and low M Score. (F) RFS curve of patients with late‐stage CRC categorized by high and low M Score. The cut‐off value for high M Score = 33.15.