Diagnostic and prognostic value of CD44v9 and TIM3 expression in CK(‑) and CK(+) regions in gastric cancer tissues.

The specificity and sensitivity of the current diagnostic and prognostic biomarkers for gastric cancer (GC) are limited. The present study aimed to evaluate the diagnostic and prognostic significance of cluster-of-differentiation gene 44 variant isoform 9 (CD44v9) and T cell immunoglobulin and mucin domain-containing protein 3 (TIM3) expression levels alone or combined in the tumor tissues of patients with GC and reveal the roles of CD44v9 and TIM3 in the cytokeratin (CK)(+) and CK(-) regions. Multiplex immunofluorescence staining was performed for CD44v9, TIM3 and CK using a tissue microarray. The tissues were divided into three regions based on CK expression: Total, CK(+), and CK(-) regions. The diagnostic and prognostic value was evaluated using receiver operating characteristic curves, Kaplan-Meier and Cox regression analyses. The results demonstrated that the density of cells expressing CD44v9, TIM3 and co-expressing CD44v9 and TIM3 (CD44v9/TIM3) in both the CK(+) and CK(-) regions of tumor tissues was significantly higher than those in normal tissues (P<0.001). Moreover, the expression of CD44v9 in the CK(-) region was significantly positively correlated with age and tumor grade (P<0.05), and the expression of CD44v9/TIM3 in the CK(-) region of tumor tissues was significantly positively correlated with age, tumor grade and metastasis (P<0.05). Furthermore, the area under the curve for TIM3 expression in the CK(+) region was 0.709, with a sensitivity of 45.83% and a specificity of 85.54% (P<0.001). High expression of CD44v9 in the CK(-) region was also significantly associated with poor survival and independently predicted a poor prognosis in patients with GC (hazard ratio, 2.387; 95% confidence interval, 1.384-4.118; P<0.01). In conclusion, dividing tissue regions based on CK expression is important for the diagnosis of GC. The expression of TIM3 in the CK(+) region demonstrated diagnostic potential for GC, and high expression of CD44v9 in the CK(-) region was an independent prognostic risk factor for patients with GC.