Wang Xiaofei, Lu Lin, Yang Ruidong, Wang Zhiwu, Li Qingke, Li Jingwu, Liu Yankun
School of Clinical Medicine, North China University of Science and Technology, Tangshan, Hebei 063200, P.R. China.
Department of Medical Molecular Diagnosis, Tangshan People's Hospital, Tangshan, Hebei 063001, P.R. China.
Oncol Lett. 2024 Aug 6;28(4):479. doi: 10.3892/ol.2024.14612. eCollection 2024 Oct.
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.
目前用于胃癌（GC）诊断和预后评估的生物标志物的特异性和敏感性有限。本研究旨在评估分化簇基因44变异体9（CD44v9）和含T细胞免疫球蛋白和粘蛋白结构域蛋白3（TIM3）单独或联合在GC患者肿瘤组织中的表达水平对诊断和预后的意义，并揭示CD44v9和TIM3在细胞角蛋白（CK）和CK区域中的作用。使用组织芯片对CD44v9、TIM3和CK进行多重免疫荧光染色。根据CK表达将组织分为三个区域：总区域、CK区域和CK区域。使用受试者工作特征曲线、Kaplan-Meier和Cox回归分析评估诊断和预后价值。结果表明，肿瘤组织的CK区域和CK区域中表达CD44v9、TIM3以及共表达CD44v9和TIM3（CD44v9/TIM3）的细胞密度显著高于正常组织（P<0.001）。此外，CK区域中CD44v9的表达与年龄和肿瘤分级显著正相关（P<0.05），肿瘤组织CK区域中CD44v9/TIM3的表达与年龄、肿瘤分级和转移显著正相关（P<0.05）。此外，CK区域中TIM3表达的曲线下面积为0.709，敏感性为45.83%，特异性为85.54%（P<0.001）。CK区域中CD44v9的高表达也与较差的生存率显著相关，并独立预测GC患者预后不良（风险比，2.387；95%置信区间，1.384-4.118；P<0.01）。总之，基于CK表达划分组织区域对GC的诊断很重要。CK区域中TIM3的表达显示出对GC的诊断潜力，CK区域中CD44v9的高表达是GC患者独立的预后危险因素。
