CD44v9 Expression in Pretreatment Biopsies as a Predictor of Chemotherapy Resistance in Gastric Cancer

TL;DR

CD44v9 expression in pretreatment biopsies may predict chemotherapy resistance in gastric cancer patients, helping guide personalized treatment.

Contribution

CD44v9 is identified as a potential biomarker for chemoresistance in gastric cancer pretreatment biopsies.

Findings

High CD44v9 expression was significantly associated with poor histological response to chemotherapy (p = 0.046).

Poor histological response predicted worse prognosis (p = 0.045).

Conversion surgery and poor histological response were independent predictors of poor outcomes in multivariate analysis.

Abstract

Gastric cancer remains a major global health burden, and responses to neoadjuvant chemotherapy (NAC) and conversion surgery vary owing to chemoresistance. Cancer stem cells (CSCs) exhibit self-renewal and drug resistance, influencing treatment efficacy and prognosis. Among CSC markers, CD44 variant 9 (CD44v9) is notable for its role in redox regulation and chemoresistance. This study evaluated CD44v9 expression in pretreatment biopsies from 84 patients with gastric cancer treated with NAC or conversion surgery. High CD44v9 expression (25%) was significantly associated with a poor histological response (p = 0.046). Kaplan–Meier analysis confirmed that a poor histological response predicted a worse prognosis (p = 0.045). In the multivariate Cox analysis, conversion surgery (p = 0.018) and poor histological response (p = 0.011) were independent predictors of poor prognosis. These findings suggest that CD44v9 expression levels in pretreatment biopsies may serve as a predictive biomarker of chemoresistance, guiding individualized treatment strategies.

Background: Gastric cancer is a major global health burden. Although neoadjuvant chemotherapy and conversion surgery can improve survival, treatment responses vary owing to chemotherapy resistance. Cancer stem cells (CSCs), characterized by self-renewal and drug resistance, are closely linked to treatment efficacy and prognosis. Among these, CD44 variant 9 (CD44v9) plays an important role in redox regulation and chemoresistance. Although its expression in resected gastric cancer specimens has been associated with poor prognosis, little is known about its expression in pretreatment biopsies and its relationship with therapeutic responses. This study aimed to clarify the predictive value of CD44v9 expression in gastric cancer biopsy specimens. Methods: Pretreatment biopsy specimens from 84 patients with gastric cancer who underwent neoadjuvant chemotherapy or conversion surgery at our institution were analyzed. Associations between CD44v9 expression, histological response, and prognosis were evaluated. Results: High CD44v9 expression was observed in 25% of patients and was significantly associated with a poor histological response (p = 0.046). Although CD44v9 expression was not directly linked to prognosis, a poor histological response correlated with worse survival (p = 0.045). In the multivariate analysis, conversion surgery (p = 0.018) and poor histological response (p = 0.011) were identified as independent predictors of poor outcomes. Conclusions: Evaluation of CD44v9 expression in pretreatment biopsies may help predict chemotherapy resistance in patients with gastric cancer. This biomarker assessment could guide individualized treatment strategies and improve patient management outcomes.

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