Department of Hepatopancreatobiliary Surgery, Peking University Shougang Hospital, Beijing, China.
Department of Hepatobiliary Surgery, The Fourth Medical Center of PLA General Hospital, Beijing, China.
Lab Med. 2022 Nov 3;53(6):561-569. doi: 10.1093/labmed/lmac036.
The prognostic markers of hepatocellular carcinoma (HCC) patients with bone metastasis are of great significance for the design of treatment strategy, the maintenance of life quality of the patients, and the improvement of cancer prognosis. MicroRNA-149 (miR-149) rs2292832 C/T polymorphism in HCC patients has been reported to be associated with the risk of HCC, but whether it can predict the prognosis of HCC patients with bone metastasis remains unclear. The goal of our study was to examine the prognostic impact of miR-149 rs2292832 C/T polymorphism on HCC patients with bone metastasis.
A total of 67 cases of HCC patients with bone metastasis (BC group) and 73 cases of HCC patients without bone metastasis (NC group) were included in this study. The miR-149 levels in blood leukocytes and tumor tissues were determined by qRT-PCR. Genotyping analysis of miR-149 rs2292832 was performed using polymerase chain reaction (PCR)-restriction fragment length polymorphism assay.
The blood leukocyte miR-149 levels were significantly decreased in HCC patients, compared with the healthy controls, and they were significantly decreased in the BC patients, compared with the NC cases. BC patients carrying miR-149 rs2292832 CC+CT phenotype have a better overall survival (OS) rate, whereas no significant correlation was found between miR-149 rs2292832 CC+CT phenotype and the OS rate in NC group. The miR-149 rs2292832 CC+CT phenotype was correlated with certain bone turnover markers and bone metabolism markers but was not correlated with receptor activator of nuclear factor-kappaB ligand (RANKL) expression. Meanwhile, the combination of miR-149 rs2292832 CC+CT phenotype and RANKL expression could improve the prognosis assessment of HCC patients with bone metastasis.
miR-149 rs2292832 polymorphism might be a novel prognostic biomarker for HCC patients with bone metastasis. A follow-up study with a larger cohort from a multicenter should be performed to test our conclusions.
肝细胞癌（HCC）患者骨转移的预后标志物对于治疗策略的设计、患者生活质量的维持以及癌症预后的改善具有重要意义。已有研究报道，miR-149（miR-149）rs2292832 在 HCC 患者中的 C/T 多态性与 HCC 的发病风险相关，但它是否可以预测 HCC 骨转移患者的预后尚不清楚。本研究旨在探讨 miR-149 rs2292832 C/T 多态性对 HCC 骨转移患者的预后影响。
本研究共纳入 67 例 HCC 骨转移患者（BC 组）和 73 例 HCC 无骨转移患者（NC 组）。采用 qRT-PCR 检测血液白细胞和肿瘤组织中的 miR-149 水平。采用聚合酶链反应（PCR）-限制性片段长度多态性分析检测 miR-149 rs2292832 的基因分型。
与健康对照组相比，HCC 患者血液白细胞中的 miR-149 水平显著降低，与 NC 组相比，BC 患者血液白细胞中的 miR-149 水平显著降低。携带 miR-149 rs2292832 CC+CT 表型的 BC 患者总生存（OS）率较高，而 miR-149 rs2292832 CC+CT 表型与 NC 组的 OS 率之间无显著相关性。miR-149 rs2292832 CC+CT 表型与某些骨转换标志物和骨代谢标志物相关，但与核因子κB 受体激活剂配体（RANKL）表达无关。同时，miR-149 rs2292832 CC+CT 表型与 RANKL 表达的结合可改善 HCC 骨转移患者的预后评估。
miR-149 rs2292832 多态性可能是 HCC 骨转移患者的一种新的预后生物标志物。应进行一项更大队列的多中心随访研究来验证我们的结论。
