Bonatelli Murilo, Fornari Isabella Fernandes, Bernécule Priscila Neves, Pinheiro Lara Esquiapatti, Costa Ricardo Filipe Alves, Longatto-Filho Adhemar, Junior João Neif Antonio, Silva Eduardo Caetano Albino, Cárcano Flávio Mavignier, Pinheiro Céline
Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil.
Barretos School of Health Sciences Dr. Paulo Prata-FACISB, Barretos, Brazil.
Front Oncol. 2021 Jun 24;11:682665. doi: 10.3389/fonc.2021.682665. eCollection 2021.
Cancer of unknown primary origin (CUP) is defined as metastatic cancer without identification of the primary site. Considering that only 15-20% of patients with CUP show a favorable outcome, identifying biomarkers may help improve the clinical management of patients who do not respond well to conventional therapies. In this context, the study of the metabolic profile of CUP may pave the way to establish new biomarkers and/or therapeutic targets; therefore, this study aimed to characterize the expression of metabolism-related proteins in CUP.
The expression of monocarboxylate transporters MCT1, MCT2 and MCT4, their chaperone CD147, the glucose transporter GLUT1 and the pH regulator CAIX was evaluated by immunohistochemistry in a series of 118 CUP patients, and the results were associated with the available clinicopathological information.
The metabolism-related proteins MCT1, MCT4, CD147, GLUT1 and CAIX were expressed in a critical portion of the CUP (approximately 20 to 70%). MCT1 and CD147 were both more frequently expressed in cases with lymph nodes as metastasis dominant sites ( = 0.001) as well as in samples from lymph nodes (0.001 and = 0.002, respectively), while MCT1 expression was more frequently expressed in squamous cell carcinomas ( = 0.045). A higher overall survival was observed in patients with tumors positive for GLUT1 and CAIX expression ( = 0.011 and = 0.041, respectively), but none of the proteins was an independent prognostic factor for overall survival in multivariable analysis.
The results suggest that a portion of CUPs present a hyperglycolytic phenotype, which is associated with higher overall survival.
原发灶不明的癌症（CUP）被定义为未明确原发部位的转移性癌症。鉴于仅有15% - 20%的CUP患者预后良好，鉴定生物标志物可能有助于改善对传统疗法反应不佳的患者的临床管理。在此背景下，对CUP代谢谱的研究可能为建立新的生物标志物和/或治疗靶点铺平道路；因此，本研究旨在表征CUP中代谢相关蛋白的表达。
通过免疫组织化学评估了118例CUP患者系列中一元羧酸转运蛋白MCT1、MCT2和MCT4、它们的伴侣蛋白CD147、葡萄糖转运蛋白GLUT1和pH调节剂CAIX的表达，并将结果与可用的临床病理信息相关联。
代谢相关蛋白MCT1、MCT4、CD147、GLUT1和CAIX在相当一部分CUP中表达（约20%至70%）。MCT1和CD147在以淋巴结为转移优势部位的病例中更频繁表达（分别为P = 0.001）以及在淋巴结样本中（分别为P = 0.001和P = 0.002），而MCT1表达在鳞状细胞癌中更频繁（P = 0.045）。在GLUT1和CAIX表达阳性的肿瘤患者中观察到更高的总生存率（分别为P = 0.011和P = 0.041），但在多变量分析中，没有一种蛋白是总生存的独立预后因素。
结果表明一部分CUP呈现高糖酵解表型，这与更高的总生存率相关。
