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血浆外泌体VPS37C联合血清糖类抗原125、碱性磷酸酶在转移性结直肠癌诊断中的临床价值
荣汶青,邵诗芸,浦匀舟,季青*,朱惠蓉*
0
(上海中医药大学附属曙光医院肿瘤科, 上海 201203
*通信作者)
摘要:
目的 评估血浆外泌体液泡蛋白分选蛋白37C(VPS37C)联合血清肿瘤标志物糖类抗原125(CA125)及碱性磷酸酶(ALP)检测在区分转移性结直肠癌(mCRC)与非转移性结直肠癌(nmCRC)患者中的临床意义。方法 选取2020年12月至2022年9月于上海中医药大学附属曙光医院就诊、经病理学及影像学明确诊断为结直肠癌的患者85例作为研究对象,其中nmCRC患者46例、mCRC患者39例。另选取17例同期于上海中医药大学附属曙光医院进行健康体检的志愿者作为健康对照。通过透射电子显微镜和蛋白质印迹法分析鉴定血浆中分离的外泌体。检测循环血浆外泌体VPS37C和血清CA125、ALP的表达水平,绘制ROC曲线分析这3个指标单独及联合检测对mCRC的临床诊断效能。结果 血浆外泌体VPS37C、血清CA125、血清ALP在mCRC患者中均升高(P<0.05,P<0.01);三者在结直肠癌TNM Ⅳ期患者中的表达均高于0~Ⅲ期患者(P<0.05,P<0.01);3个指标两两联合或三者联合对mCRC的诊断效能高于任一指标单独使用的效果,三者联合时的诊断效能最佳,特异度为90.91%,准确度为78.69%,AUC为0.813 9(95% CI 0.697 0~0.930 7,P<0.000 1)。结论 循环外泌体VPS37C可能是有价值的mCRC诊断标志物,并且联合血清CA125及ALP对于mCRC具有更佳的临床诊断价值。
关键词:  外泌体  液泡蛋白分选蛋白  糖类抗原125  碱性磷酸酶  结直肠肿瘤  诊断标志物
DOI:10.16781/j.CN31-2187/R.20230030
投稿时间:2023-02-04修订日期:2023-04-17
基金项目:国家自然科学基金重点项目(82030118),国家自然科学基金面上项目(82274297,82074225),上海市进一步加快中医药传承创新发展三年行动计划(2021-2023年)[ZY(2021-2023-0208)],上海市炎癌转化病证生物学前沿研究基地项目(2021KJ03-12).
Clinical value of plasma exosomal VPS37C combined with serum carbohydrate antigen 125 and alkaline phosphatase in diagnosis of metastatic colorectal cancer
RONG Wenqing,SHAO Shiyun,PU Yunzhou,JI Qing*,ZHU Huirong*
(Department of Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
*Corresponding authors)
Abstract:
Objective To evaluate the clinical significance of plasma exosomal vacuolar protein sorting-associated protein 37C (VPS37C) combined with serum tumor markers carbohydrate antigen 125 (CA125) and alkaline phosphatase (ALP) in distinguishing patients with metastatic colorectal cancer (mCRC) or non-metastatic colorectal cancer (nmCRC). Methods A total of 85 patients who were diagnosed with colorectal cancer through pathology and imaging in Shuguang Hospital, Shanghai University of Traditional Chinese Medicine from Dec. 2020 to Sep. 2022 were selected, including 46 patients with nmCRC and 39 with mCRC. Another 17 volunteers who underwent physical examination in Shuguang Hospital, Shanghai University of Traditional Chinese Medicine during the same period were selected as healthy controls. The exosomes isolated from circulating plasma were identified by transmission electron microscopy and Western blotting. The levels of plasma exosomal VPS37C, serum CA125 and ALP were detected, and the clinical diagnostic efficacies of these 3 indicators alone or in combination for mCRC were analyzed using receiver operating characteristic curves. Results The levels of plasma exosomal VPS37C, serum CA125 and ALP were increased in the mCRC patients (P<0.05, P<0.01). The expression of the 3 indicators in colorectal cancer TNM stage Ⅳ patients was higher than that in TNM stage 0-Ⅲ patients (P<0.05, P<0.01). The diagnostic efficacy of the combination of the 2 or 3 indicators for mCRC was higher than that of any single indicator. The combination of the 3 indicators had the best diagnostic efficacy, with a specificity of 90.91%, an accuracy of 78.69%, and an area under curve of 0.813 9 (95% confidence interval 0.697 0-0.930 7, P<0.000 1). Conclusion Circulating plasma exosomal VPS37C may be a valuable diagnostic marker for mCRC, and its combination with serum CA125 and ALP has better clinical diagnostic value.
Key words:  exosome  vacuolar protein sorting-associated protein 37C  carbohydrate antigen 125  alkaline phosphatase  colorectal neoplasms  diagnostic markers