Yorita Kenji, Ohno Akinobu, Nishida Takahiro, Kondo Kazuhiro, Ohtomo Toshihiko, Kataoka Hiroaki
Section of Oncopathology and Regenerative Biology, Department of Pathology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan.
Community Medical Center, University of Miyazaki Hospital, Miyazaki, Japan.
BMC Res Notes. 2019 Nov 9;12(1):741. doi: 10.1186/s13104-019-4778-y.
We previously reported the identification of monocarboxylate transporter 4 (MCT4) and glypican-3 (GPC3) as prognostic factors for hepatocellular carcinoma (HCC), which are now considered significant poor prognostic factors for the disease. This study aimed to clarify the detailed interaction of these two factors in HCC to improve our understanding of aggressive HCC phenotypes. A total of 225 Japanese patients with HCC from our previous study were subjected to immunohistochemical analyses.
The number of MCT4-positive (MCT4+) HCC cases was 47 (21%), and most MCT4+ HCC showed high GPC3 expression (94%, 44/47 cases). In 44 MCT4+/GPC3+ HCC cases, intratumoral heterogeneity of GPC3 or MCT4 expression was further evaluated. We observed reciprocal (inverse), synergistic, mixed reciprocal and synergistic, or irrelevant interaction of MCT4 and GPC3 expression in 29 (66%), 5 (11%), 1 (2%), and 9 cases (21%), respectively. The cases exhibiting reciprocal expression of both markers tended to have cirrhosis without a history of neoadjuvant therapy. In summary, although MCT4+ HCC cases are mostly GPC3+, intratumoral expression patterns of MCT4 and GPC3 are frequently reciprocal each other, suggesting that dual targeting of MCT4 and GPC3 may achieve a better antitumor effect for MCT4+ HCC cases.
我们之前报道了已鉴定出单羧酸转运蛋白4（MCT4）和磷脂酰肌醇蛋白聚糖-3（GPC3）作为肝细胞癌（HCC）的预后因素，它们现在被认为是该疾病显著的不良预后因素。本研究旨在阐明这两个因素在HCC中的详细相互作用，以增进我们对侵袭性HCC表型的理解。对我们之前研究中的225例日本HCC患者进行了免疫组织化学分析。
MCT4阳性（MCT4+）的HCC病例有47例（21%），大多数MCT4+的HCC显示GPC3高表达（94%，44/47例）。在44例MCT4+/GPC3+的HCC病例中，进一步评估了GPC3或MCT4表达的肿瘤内异质性。我们分别在29例（66%）、5例（11%）、1例（2%）和9例（21%）中观察到MCT4和GPC3表达呈相互（反向）、协同、混合相互和协同或不相关的相互作用。两种标志物呈相互表达的病例往往有肝硬化且无新辅助治疗史。总之，虽然MCT4+的HCC病例大多为GPC3+，但MCT4和GPC3的肿瘤内表达模式经常相互反向，这表明对MCT4和GPC3进行双重靶向可能对MCT4+的HCC病例产生更好的抗肿瘤效果。
