In hepatocellular carcinomas (HCCs), the role of the cell surface protein V-set and immunoglobulin domain containing 1 (VSIG1), which is known as a specific marker of the gastric mucosa and testis, has not yet been determined. We examined VSIG1 immunohistochemical (IHC) expression in 105 consecutive samples provided by HCC patients, along with the IHC expression of three of the biomarkers known to be involved in the epithelial–mesenchymal transition (EMT): vimentin (VIM), and E- and N-cadherin (encoded by CDH1 and CDH2 genes). IHC subcellular localization of thyroid transcription factor 1 (TTF1), in which nuclear-to-cytoplasmic translocation is known to cause a lineage shift from lung to gastric-type adenocarcinoma, was also checked. The obtained data were validated using the miRNET program. In the examined HCC samples, VSIG1 expression was observed in the cytoplasm of normal hepatocytes and downregulated in 47 of the 105 HCCs (44.76%). In 29 cases (27.62%), VSIG1 was co-expressed with cytoplasmic TTF1. VSIG1 expression was positively correlated with both E-cadherin and N-cadherin and negatively correlated with VIM (p < 0.0001). The VSIG1+/E-cadherin+/N-cadherin-/VIM phenotype was seen in 13 cases (12.4%) and was characteristic of well-differentiated (G1/2) carcinomas diagnosed in pT1/2 stages. Like pulmonary carcinomas, simultaneous cytoplasmic positivity of HCC cells for VSIG1 and TTF1 may be a potential indicator of a lineage shift from conventional to gastric-type HCC. The E-cadherin/VSIG1 complex can help suppress tumor growth by limiting HCC dedifferentiation. The miRNET-based interaction between VSIG1/VIM/CDH1/CDH2 genes might be interconnected by miR-200b-3p, a central regulator of EMT which also targets VIM and VSIG1.

在肝细胞癌 (HCC) 中，细胞表面蛋白 V-set 和含有免疫球蛋白结构域 1 (VSIG1) 的作用尚未确定，VSIG1 被称为胃黏膜和睾丸的特异性标志物。我们检查了 HCC 患者提供的 105 个连续样本中的 VSIG1 免疫组织化学 (IHC) 表达，以及已知参与上皮-间质转化 (EMT) 的三种生物标志物的 IHC 表达：波形蛋白 (VIM) 和 E-和N-钙粘蛋白（由 CDH1 和 CDH2 基因编码）。还检查了甲状腺转录因子 1 (TTF1) 的 IHC 亚细胞定位，其中已知核到细胞质的易位会导致从肺到胃型腺癌的谱系转变。使用 miRNET 程序验证获得的数据。在检查的 HCC 样本中，在正常肝细胞的细胞质中观察到 VSIG1 表达，并在 105 个 HCC 中的 47 个（44.76%）中下调。在 29 例 (27.62%) 中，VSIG1 与细胞质 TTF1 共表达。VSIG1 表达与 E-cadherin 和 N-cadherin 均呈正相关，与 VIM 呈负相关（p  < 0.0001)。VSIG1+/E-cadherin+/N-cadherin-/VIM 表型见于 13 例 (12.4%) 并且是在 pT1/2 期诊断的高分化 (G1/2) 癌的特征。与肺癌一样，HCC 细胞同时对 VSIG1 和 TTF1 呈阳性可能是从传统 HCC 向胃型 HCC 谱系转变的潜在指标。E-cadherin/VSIG1 复合物可以通过限制 HCC 去分化来帮助抑制肿瘤生长。VSIG1/VIM/CDH1/CDH2 基因之间基于 miRNET 的相互作用可能通过 miR-200b-3p 相互连接，miR-200b-3p 是 EMT 的中心调节因子，也针对 VIM 和 VSIG1。