结直肠癌组织Netrin-1、UNC5B联合综合病理风险指标对患者3年生存结局的预测价值OA

Objective To investigate the expression of Netrin-1 and unc-5 netrin receptor B(UNC5B)in colorectal cancer(CRC)tissues and their associations with clinicopathological characteristics and survival out-come,and to evaluate the predictive performance of a model incorporating Netrin-1 and UNC5B expression and a composite pathological risk index for 3-year survival outcome in patients with CRC.Methods A single-cen-ter retrospective cohort study was conducted involving 122 patients with CRC who underwent curative resec-tion at the hospital from May 2020 to July 2022.Immunohistochemistry was performed to detect Netrin-1 and UNC5B expression in CRC tissues and paired adjacent non-tumor tissues,and the positive expression rates be-tween the two tissue types were compared using the McNemar test.Survival curves were generated using the Kaplan-Meier method,and between-group differences were assessed using the log-rank test.Factors associated with survival outcome in patients with CRC were identified using a multivariate Cox regression model.A com-bined risk score model was constructed based on Netrin-1,UNC5B and a composite pathological risk index.The predictive performance of the individual-marker model and the combined model was evaluated using time-dependent receiver operating characteristic(ROC)curves at 3-year after surgery,and internal validation was performed using 1 000 bootstrap resamples.Results The positive expression rate of Netrin-1 was 65.57%(80/122)in CRC tissues,which was higher than that in paired adjacent non-tumor tissues[9.84%(12/122)].Similarly,the positive expression rate of UNC5B was 67.21%(82/122)in CRC tissues,which was higher than that in paired adjacent non-tumor tissues[8.20%(10/122)];both differences were statistically significant(P<0.001).The positive expression rates of Netrin-1 and UNC5B proteins in tumor tissues were significantly higher in patients with TNM stage Ⅲ disease than in those with stage Ⅰ-Ⅱ disease,in patients with high-grade tumor budding than in those with low-grade tumor budding,in patients with a high tumor stromal proportion than in those with a low tumor stromal proportion,and in patients with lymphovascular in-vasion than in those without lymphovascular invasion(P<0.05).Significant differences in overall survival were observed between patients with positive and negative Netrin-1 expression and between those with posi-tive and negative UNC5B expression(log-rank χ2=12.500 and 14.320,respectively;both P<0.001).Multi-variate Cox regression analysis showed that increased Netrin-1 expression,increased UNC5B expression and a high composite pathological risk index were independently associated with an increased risk of death(P=0.004,0.002,0.003).At 3-year after surgery,the time-dependent areas under the receiver operating charac-teristic curve for the three-item combined model,the Netrin-1 single-marker model,and the UNC5B single-marker model were 0.904(95%CI:0.860-0.943),0.826(95%CI:0.801-0.854),and 0.810(95%CI:0.780-0.849)respectively.Conclusion Netrin-1 and UNC5B are highly expressed in CRC tissues and are associated with aggressive pathological features.The combination of Netrin-1 and UNC5B expression with a composite pathological risk index shows good discrimination for 3-year survival outcome in patients with CRC and may have potential value for prognostic risk stratification.