中国医学科学院学报2025，Vol.47Issue(6)：896-909,14.DOI:10.3881/j.issn.1000-503X.16518
老年结直肠癌患者阿片类生长因子及阿片类生长因子受体和P16、P21蛋白表达及与临床病理特征的相关性
Expression of Opioid Growth Factor,Opioid Growth Factor Receptor,P16,and P21 and Their Correlations With Clinicopathological Characteristics in Elderly Patients With Colorectal Cancer
摘要
Abstract
Objective To investigate the expression of opioid growth factor(OGF),OGF receptor(OGFR),P16,and P21 in elderly patients with colorectal cancer and their correlations with clinicopathological characteristics.Methods Bioinformatic analysis of OGFR was performed via differential expression analysis,survival analysis,single-cell RNA sequencing,and spatial transcriptomics.A total of 167 elderly patients with colorectal cancer were enrolled,with 30 fresh tissue samples collected from January 2023 to December 2024 and 137 paraffin-embedded tissue samples collected from January 2016 to January 2020.All the specimens were col-lected from confirmed cases at the First Affiliated Hospital of Hebei North University.OGF expression in the 30 fresh tissue samples was detected by ELISA,while the protein levels of OGFR,P16,and P21 were measured by Western blot.Immunohistochemistry was employed to assess OGFR,P16,and P21 expression in the 137 par-affin-embedded samples.SPSS 20.0 was used to analyze the correlations of OGFR,P16,and P21 expression with clinicopathological characteristics.The Spearman method was adopted to evaluate correlations among OGFR,P16,and P21 expression.Overall 5-year survival and differences between groups were assessed by Kaplan-Meier survival curves and the log-rank test.Results Differential expression analysis revealed that the expression of OG-FR was upregulated in colorectal cancer tissue samples(P＜0.001).Survival analysis revealed a significant correlation between high OGFR expression and poor prognosis(disease-free interval:P=0.019,disease-spe-cific survival:P=0.015).Single-cell and spatial omics analyses indicated that OGFR was primarily expressed in tumor cells.ELISA results showed that compared with that in the adjacent normal tissue,the OGF expression levels elevated in pathological stages Ⅰ(P＜0.001),Ⅱ(P=0.042),Ⅲ(P＜0.001),and Ⅳ(P=0.001).Western blot results demonstrated that compared with that in the adjacent normal tissue,the protein level of OGFR was up-regulated in pathological stages Ⅰ(P＜0.001),Ⅱ(P=0.047),Ⅲ(P=0.045),and Ⅳ(P=0.012).Compared with those in the adjacent normal tissue,the protein levels of P16 and P21 were down-regulated in pathological stages Ⅰ(P=0.001,P＜0.001),Ⅱ(P=0.031,P=0.008),Ⅲ(P=0.026,P=0.024),and Ⅳ(P=0.018,P=0.015).Immunohistochemistry results demonstrated that OGFR had higher expression in cancer tissue samples than in adjacent normal tissue samples(P＜0.001),and its expression level was correlated with T stage(P=0.047),lymph node metastasis(P=0.035),TNM stage(P=0.013),differentiation degree(P=0.043),and distant metastasis(P=0.030).Conversely,the protein levels of P16 and P21 were lower in cancer tissue samples(all P＜0.001).P16 expression was cor-related with T stage(P=0.009),lymph node metastasis(P=0.035),TNM stage(P=0.001),and dif-ferentiation degree(P=0.021).P21 expression showed correlations with T stage(P=0.009),lymph node metastasis(P=0.002),and TNMstage(P=0.046).The 5-year overall survival rate of the 137 elderly pa-tients with colorectal cancer was 55.47%.The patients with positive expression of OGFR had a lower5-year over-all survival rate than those with negative expression(P=0.001).The patients with negative expression of P16 or P21 had a lower 5-year overall survival rate than those with positive expression(P16:P＜0.001;P21:P=0.007).Conclusions In the colorectal cancer tissue of elderly patients,the expression of OGFR was negative-ly correlated with that of P16 and P21.The OGF-OGFR signaling pathway may promote colorectal cancer progres-sion by suppressing P16 and P21 expression.The combined detection of these markers shows potential as a valua-ble reference for assessing disease progression.关键词
阿片类生长因子/阿片类生长因子受体/结直肠癌/P16/P21Key words
opioid growth factor/opioid growth factor receptor/colorectal cancer/P16/P21分类
医药卫生引用本文复制引用
WANG Zeyu,ZHANG Benchang,ZHANG Hao,ZHANG Yixuan,WU Xueliang,WANG Yu,QIAO Tingting,HAO Xiuqing,YAN Juan..老年结直肠癌患者阿片类生长因子及阿片类生长因子受体和P16、P21蛋白表达及与临床病理特征的相关性[J].中国医学科学院学报,2025,47(6):896-909,14.基金项目
河北省自然科学基金(H2021405002) （H2021405002）
