目的检测缺氧诱导因子1α(hypoxia-inducible factor 1α,HIF-1α)和2型谷氨酰胺酶(glutaminase 2,GLS2)在结直肠癌中的表达,探讨其临床意义。方法 应用免疫组化法检测本院结直肠癌术后108例组织标本(其中23例含癌旁黏膜组织)中HIF-1α和GLS2的表达,分析二者的表达与临床病理参数的相关性;采用Spearman等级相关分析检测HIF-1α和GLS2表达的相关性,Kaplan-Meier法分析结直肠癌中HIF-1α和GLS2的表达与患者预后的关系,Cox回归模型分析结直肠癌患者预后的影响因素。结果结直肠癌组织中HIF-1α和GLS2的表达均高于癌旁黏膜组织,差异有统计学意义(P〈0.01)。HIF-1α的表达与结直肠癌患者年龄、TNM分期、淋巴结转移、术后远处转移密切相关(P〈0.05),而GLS2的表达与结直肠癌患者年龄、浸润深度、术后远处转移密切相关(P〈0.05)。HIF-1α和GLS2的表达显著正相关(r=0.464,P〈0.01),且均与结直肠癌的预后有关,Cox回归分析显示TNM分期、术后远处转移及HIF-1α、GLS2的表达均是结直肠癌预后的独立影响因素(P〈0.05)。结论结直肠癌患者中HIF-1α、GLS2高表达预后均较低表达差,提示二者在结直肠癌的发生、发展中可能发挥重要作用。
Objective To determine the expression levels of hypoxia-inducible factor 1α (HIF-1α) and glutaminase 2 (GLS2) in colorectal cancer and explore their clinical significance. Methods Immunohistochemical staining was applied for the detection of HIF-1α and GLS2 in 108 samples of colorectal cancer and 23 adjacent mucosa tissues obtained through surgical treatment. The correlation between the expression of HIF-1α and GLS2 and clinicopathological features of patients with colorectal cancer was analyzed. Spearman rank correlation was used to detect the correlation between HIF-1α expression and GLS2 expression,Kaplan-Meier survival analysis was used to evaluate the impact of HIF-1α and GLS2 expression on postoperative survival of the patients with colorectal cancer. Cox univariate and multivariate prognostic analysis was utilized to explore the prognostic factors of the patients with colorectal cancer. Results The expression levels of HIF-1α and GLS2 were both significantly higher than in adjacent mucosa tissues (P〈0.01). HIF-1α expression was closely correlated with age, TNM stage, lymphatic metastasis and postoperative distant metastasis (P〈0.05), and GLS2 expression was closely correlated with age, invasion depth and postoperative distant metastasis (P〈0.05). Spearman rank correlation analysis indicated that HIF-1α and GLS2 expression were positively correlated with the prognosis of colorectal cancer (r=0.464, P〈0.01). Multivariate Cox analysis revealed that TNM stage, postoperative distant metastasis, and expression of HIF-1α and GLS2 played significant roles in the prediction of patient’s prognosis (P〈0.05). Conclusion High expression of HIF-1α and GLS2 predicts poor prognosis in the patients with colorectal cancer, indicating that they might play important roles in the occurrence and progression of the disease.