老年结直肠癌病人癌组织中SKp2、P27Kip1、HLA-DRA蛋白表达情况及与预后的关系

doi:10.3969/j.issn.1003-9198.2025.05.015

摘要/Abstract

摘要： 目的探究老年结直肠癌(CRC)病人癌组织中S期激酶相关蛋白2(SKp2)、P27Kip1、人白细胞抗原(HLA)-DRA蛋白表达情况及其与预后的关系。方法选取开滦总医院林西医院2019年1月至2021年5月收治的154例老年CRC病人为研究对象。采用免疫组化法检测病人癌组织及癌旁组织中SKp2、P27Kip1、HLA-DRA蛋白的表达情况。对病人进行3年随访,采用Kaplan-Meier法绘制癌组织中SKp2、P27Kip1、HLA-DRA阳性表达与阴性表达病人的生存曲线;采用多因素Cox回归分析老年CRC病人预后的影响因素。结果与癌旁组织相比,癌组织中SKp2和HLA-DRA蛋白阳性表达率较高(P＜0.001),P27Kip1阳性表达率较低(P＜0.001)。癌组织中SKp2、HLA-DRA表达与CRC病人肿瘤分化程度有关(P＜0.01),P27Kip1表达与肿瘤最大直径有关(P＜0.05),SKp2、P27Kip1、HLA-DRA表达与TNM分期有关(P＜0.01)。随访36个月时,失访5例,97例病人存活(生存组),52例病人死亡(死亡组)。与生存组相比,死亡组低分化、TNM分期Ⅲ~Ⅳ期、SKp2阳性比例、HLA-DRA阳性比例显著增高(P＜0.05),P27Kip1阳性比例显著降低(P＜0.01)。SKp2阳性表达者3年总生存率(57.38%)低于SKp2阴性表达者(84.38%)(P＜0.05);P27Kip1阳性表达者3年总生存率高于P27Kip1阴性表达者(77.55%比56.19%,P＜0.01);HLA-DRA阳性表达者3年总生存率低于HLA-DRA阴性表达者(57.52%比78.05%,P＜0.01)。多因素Cox回归分析结果显示,低分化(HR=1.213)、TNM分期为Ⅲ~Ⅳ期(HR=1.837)、SKp2阳性(HR=1.465)、HLA-DRA阳性(HR=1.224)为老年CRC病人预后不良的独立危险因素,P27Kip1阳性(HR=0.952)为保护因素。结论老年CRC病人癌组织中SKp2和HLA-DRA阳性表达率高,P27Kip1阳性表达率低,SKp2、P27Kip1、HLA-DRA表达情况与病人病理特征及预后密切相关。

关键词: 结直肠癌, 预后, S期激酶相关蛋白2, P27Kip1, 人白细胞抗原-DRA, 老年人

Abstract: Objective To investigate the expression of S-phase kinase-associated protein 2 (SKp2), P27Kip1, and human leukocyte antigen (HLA)-DRA protein in cancer tissues of elderly patients with colorectal cancer (CRC) and their relationship with prognosis. Methods From January 2019 to May 2021, 154 elderly CRC patients who were adimitted to Linxi Hospital of Kailuan General Hospital were enrolled in this study. Immunohistochemistry was applied to detect the expression of SKp2, P27Kip1, and HLA-DRA proteins in the cancer tissues and adjacent tissues of elderly CRC patients. Patients were followed up for 3 years, and Kaplan-Meier method was used to plot the survival curves of the patients with positive expression and negative expression of SKp2, P27Kip1 and HLA-DRA in the cancer tissue. Multivariate Cox regression was applied to analyze the influencing factors of prognosis in the elderly CRC patients. Results Compared with adjacent tissues, the positive expression rates of SKp2 and HLA-DRA proteins were higher, and the positive expression rate of P27Kip1 was lower in CRC cancer tissues (P<0.001). The expression of SKp2 and HLA-DRA in the elderly CRC patients was related to the degree of tumor differentiation in the cancer tissue (P<0.01), the expression of P27Kip1 was related to the maximum tumor diameter in the cancer tissue (P<0.05), and the expression of SKp2, P27Kip1, and HLA-DRA was related to TNM staging in the cancer tissue (P<0.01). During the 36-month follow-up, 5 cases were lost to follow-up, 97 patients survived (survival group), and 52 patients died (death group). Compared with the survival group, the proportions of poorly differentiated, TNM stage Ⅲ-Ⅳ, SKp2 positive expression, and HLA-DRA positive expression in the death group were significantly higher (P<0.05), while the proportion of P27Kip1 positive expression was significantly lower (P<0.01). The 3-year overall survival rate of the patients with SKp2 positive expression was lower than that of the patients with SKp2 negative expression (57.38% vs 84.38%, P<0.01); the 3-year overall survival rate of the patients with P27Kip1 positive expression was higher than that of the patients with P27Kip1 negative expression (77.55% vs 56.19%, P<0.01); the 3-year overall survival rate of the patients with positive expression of HLA-DRA was lower than that of the patients with negative expression (57.52% vs 78.05%, P<0.01). Multivariate Cox regression showed that low differentiation (HR=1.213), TNM stage Ⅲ-Ⅳ (HR=1.837), SKp2 positivity (HR=1.465), and HLA-DRA positivity (HR=1.224) were independent risk factors for poor prognosis in the elderly CRC patients, while P27Kip1 positivity (HR=0.952) was a protective factor. Conclusions The positive expression rates of SKp2 and HLA-DRA are high in the cancer tissues of elderly patients with CRC, while the positive expression rate of P27Kip1 is low. The expression of SKp2, P27Kip1 and HLA-DRA is closely related to the pathological characteristics and prognosis of the patients with CRC.

Key words: colorectal cancer, prognosis, S-phase kinase-associated protein 2, P27Kip1, human leukocyte antigen DRA, aged

中图分类号:

R 735.3

张冬梅, 张静, 赵振伟, 刘鹏, 张永健. 老年结直肠癌病人癌组织中SKp2、P27Kip1、HLA-DRA蛋白表达情况及与预后的关系[J]. 实用老年医学, 2025, 39(5): 508-513.

ZHANG Dongmei, ZHANG Jing, ZHAO Zhenwei, LIU Peng, ZHANG Yongjian. Expression of SKp2, P27Kip1 and HLA-DRA protein in cancer tissues of elderly patients with colorectal cancer and their relationship with prognosis[J]. Practical Geriatrics, 2025, 39(5): 508-513.

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