结直肠癌组织中JAK2基因突变和TCF3蛋白表达与临床病理特征及预后的相关性

The correlation between colorectal cancer tissues JAK2 gene mutations and TCF3 protein expression with clinical pathological features and prognosis

目的探讨结直肠癌组织中Janus激酶2(JAK2)基因突变和T细胞因子3(TCF3)蛋白表达与临床病理特征及预后的相关性,为结直肠癌病情和预后早期评估提供实验室参考指标。方法回顾性分析2016年1月~2021年4月收治且保留结直肠癌及癌旁组织蜡块的50例结直肠癌患者资料,收集患者的基本资料,TNM分期、淋巴结转移等临床病理特征及3年生存预后。对患者的结肠癌及癌旁组织蜡块进行检测,采用Taqman荧光探针法检测结肠癌组织JAK2基因rs2230724位点AA、AG和GG等基因型分布情况,通过免疫组化法检测结肠癌及癌旁组织TCF3蛋白阳性表达率。比较不同临床病理特征患者的基本资料、JAK2 rs2230724基因突变和TCF3蛋白表达情况,Logistics回归模型分析结肠癌临床病理特征的影响因素。采用Kaplan-Meier生存曲线分析比较结直肠癌组织JAK2基因突变和TCF3蛋白表达患者的生存预后,采用Cox回归模型分析影响结直肠癌患者预后的危险因素。结果结肠癌组织TCF3蛋白阳性表达率均高于癌旁组织(P<0.05)。TNMⅢ期结肠癌患者的年龄、BMI、结肠癌组织JAK2基因rs2230724位点GG型占比和TCF3蛋白阳性表达率均高于TNMⅠ~Ⅱ期患者(P<0.05);存在淋巴结转移结肠癌患者的年龄、BMI、吸烟率、结肠癌组织JAK2基因rs2230724位点GG型占比和TCF3蛋白阳性表达率均高于无淋巴结转移患者(P<0.05);Logistics回归模型分析结果显示,结肠癌TNM分期、淋巴结转移等临床病理特征的影响因素均为年龄、结肠癌组织JAK2基因rs2230724位点突变情况和TCF3蛋白阳性表达率(P<0.05)。Kaplan-Meier生存曲线分析结果显示,结肠癌组织JAK2基因rs2230724位点GG型和TCF3蛋白阳性患者均具有更高的累计全因死亡率(P<0.05)。单因素和多因素Cox回归模型分析结果显示,影响结直肠癌患者预后的独立危险因素有JAK2基因rs2230724位点GG型、TCF3蛋白阳性表达、TNMⅢ期、淋巴结转移和年龄等。结论结直肠癌组织中JAK2基因rs2230724位点GG型占比和TCF3蛋白表达均与其临床病理特征及预后相关,可作为结直肠癌临床病理特征评估及预后预测参考指标。

Objective To explore the correlation between colorectal cancer tissue Janus kinase 2(JAK2)gene mutations and T cytokine 3(TCF3)protein expression with clinical pathological characteristics and prognosis,and to provide laboratory reference indicators for early evaluation of the illness severity and prognosis of colorectal cancer.Methods A retrospective analysis was conducted on the data of 50 colorectal cancer patients who were admitted from January 2016 to April 2021 and retained colon cancer and adjacent tissue wax blocks.Basic information,clinical and pathological features such as TNM staging,lymph node metastasis,and 3-year survival prognosis of the patients were collected.The wax blocks of colon cancer and adjacent tissues of patients were detected,in which Taqman fluorescence probe method was applied to detect the distribution of JAK2 gene at the rs2230724 locus AA,AG,and GG genotypes in colon cancer tissues,and immunohistochemistry method was applied to detect the positive expression rate of TCF3 protein in colon cancer and adjacent tissues.The basic information,JAK2 rs2230724 gene mutation,and TCF3 protein expression of patients with different clinical and pathological characteristics were compared,and the influencing factors of clinical and pathological characteristics of colon cancer was analyzed by logistic regression model.Kaplan Meier survival curve was applied to compare the survival prognosis of patients with JAK2 gene mutations and TCF3 protein expression in colorectal cancer tissue,and Cox regression model was applied to analyze the risk factors affecting the prognosis of colorectal cancer patients.Results The positive expression rate of TCF3 protein in colon cancer tissues was higher than that in adjacent tissues(P<0.05).The age,BMI,proportion of GG genotype at rs2230724 locus of JAK2 gene and positive expression rate of TCF3 protein in TNM stageⅢcolon cancer patients were higher than those in TNM stageⅠ-Ⅱpatients(P<0.05);The age,BMI,smoking rate,proportion of GG type at the rs2230724 locus of JAK2 gene in colon cancer tissue,and positive expression rate of TCF3 protein in patients with lymph node metastasis were higher than those without lymph node metastasis(P<0.05);The results of the logistic regression model analysis showed that the influencing factors of clinical pathological features such as TNM staging and lymph node metastasis in colon cancer were age,mutation of JAK2 gene rs2230724 site in colon cancer tissue,and positive expression rate of TCF3 protein(P<0.05).The Kaplan Meier survival curve analysis showed that patients with JAK2 gene rs2230724 GG genotype and TCF3 protein positivity in colon cancer tissue had higher cumulative all-cause mortality rates(P<0.05).The results of univariate and multivariate Cox regression model analysis showed that independent risk factors affecting the prognosis of colorectal cancer patients include JAK2 gene rs2230724 site GG type,TCF3 protein positive expression,TNM stage III,lymph node metastasis,and age.Conclusion The proportion of JAK2 gene rs2230724 GG type and TCF3 protein expression in colorectal cancer tissues are related to their clinical pathological characteristics and prognosis,and can be used as reference indicators for evaluating clinical pathological characteristics and predicting prognosis of colorectal cancer.