软骨寡聚基质蛋白上调预示尿路上皮癌预后不良。
Upregulation of Cartilage Oligomeric Matrix Protein Predicts Poor Prognosis in Urothelial Carcinoma.
作者信息
Kuo Yu-Hsuan, Lai Hong-Yue, Chan Ti-Chun, Hsing Chung-Hsi, Huang Steven K, Hsieh Kun-Lin, Chen Tzu-Ju, Li Wan-Shan, Lu Jhih-Cheng, Li Chien-Feng
机构信息
Division of Hematology and Oncology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan, 71004, Taiwan.
College of Pharmacy and Science, Chia Nan University, Tainan, 71710, Taiwan.
出版信息
Onco Targets Ther. 2022 Jun 30;15:727-740. doi: 10.2147/OTT.S370028. eCollection 2022.
PURPOSE
Cartilage oligomeric matrix protein (COMP) is known as a large pentameric glycoprotein, which interacts with various extracellular matrix proteins in tissues. COMP has been reported to play a role in multiple connective tissue disorders. Recently, elevated COMP levels have been found to be associated with increased tumor size, metastases, faster recurrence of cancer, and overall poorer survival in several cancers. However, the clinical importance of COMP in urothelial carcinoma remains unclear. We investigated the association between COMP expression and clinical outcomes in urothelial carcinoma.
PATIENTS AND METHODS
In this retrospective study, we collected urothelial carcinoma (UC) tissue from 340 upper urinary tract UC (UTUC) patients and 295 urinary bladder UC (UBUC) patients. Pearson's chi-square test, Kaplan-Meier analysis, and the multivariate Cox proportional hazards model was used to examine the relationship between COMP expression and patient characteristics, pathological findings, and patient survival, such as metastasis-free survival (MFS) and disease-specific survival (DSS).
RESULTS
A total of 295 UBUC patients and 340 UTUC patients were recruited. The COMP mRNA level was significantly higher among invasive tumors (pT2-pT4) than in noninvasive tumors (pTa-T1) in UBUC groups ( < 0.01). COMP overexpression was associated with advanced T stage, nodal metastases, vascular invasion, perineural invasion, high histological grade, and high mitotic rate in both UBUC and UTUC cohorts. COMP overexpression was predictive of shorter DSS (hazard ratio [HR] in UBUC, 3.986, < 0.001; in UTUC, 2.283, = 0.027] and MFS (HR in UBUC, 6.813, < 0.001; in UTUC, 4.070, < 0.001). Kaplan-Meier analysis demonstrated high COMP expression associated with poor DSS and MFS in UTUC and UBUC groups (all < 0.0001).
CONCLUSION
COMP overexpression was linked to poor clinical prognosis and poor pathological features in UC. These results suggest COMP as a biomarker for UC.
目的
软骨寡聚基质蛋白（COMP）是一种大型五聚体糖蛋白，可与组织中的多种细胞外基质蛋白相互作用。据报道，COMP在多种结缔组织疾病中发挥作用。最近发现，COMP水平升高与几种癌症的肿瘤大小增加、转移、癌症复发加快以及总体生存率较差有关。然而，COMP在尿路上皮癌中的临床重要性仍不清楚。我们研究了COMP表达与尿路上皮癌临床结局之间的关联。
患者与方法
在这项回顾性研究中，我们收集了340例上尿路尿路上皮癌（UTUC）患者和295例膀胱尿路上皮癌（UBUC）患者的尿路上皮癌组织。采用Pearson卡方检验、Kaplan-Meier分析和多变量Cox比例风险模型来检验COMP表达与患者特征、病理结果以及患者生存率之间的关系，如无转移生存期（MFS）和疾病特异性生存期（DSS）。
结果
共招募了295例UBUC患者和340例UTUC患者。在UBUC组中，侵袭性肿瘤（pT2 - pT4）中的COMP mRNA水平显著高于非侵袭性肿瘤（pTa - T1）（<0.01）。在UBUC和UTUC队列中，COMP过表达均与晚期T分期、淋巴结转移、血管侵犯、神经周围侵犯、高组织学分级和高有丝分裂率相关。COMP过表达预示着较短的DSS（UBUC中的风险比[HR]为3.986，<0.001；UTUC中的HR为2.283，=0.027）和MFS（UBUC中的HR为6.813，<0.001；UTUC中的HR为4.070，<0.001）。Kaplan-Meier分析表明，在UTUC和UBUC组中，高COMP表达与较差的DSS和MFS相关（均<0.0001）。
结论
COMP过表达与UC的不良临床预后和不良病理特征相关。这些结果表明COMP可作为UC的生物标志物。
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