Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan, R.O.C.
School of Medicine, China Medical University Hospital, Taichung, Taiwan, R.O.C.
In Vivo. 2024 Sep-Oct;38(5):2455-2463. doi: 10.21873/invivo.13715.
BACKGROUND/AIM: Hepatocellular carcinoma (HCC) is the most common primary liver tumor and the second leading cause of cancer-related deaths worldwide. The current study aimed to investigate the clinical relevance of the epidermal growth factor-like domain multiple 6 (EGFL6) expression in HCC and to evaluate whether the expression of EGFL6 in HCC has diagnostic and prognostic significance.
This study aimed to investigate EGFL6 protein expression levels in 260 HCC tissue specimens using immunohistochemical analyses. The immunohistochemical study demonstrated strong EGFL6 expression in the cytoplasm of non-tumor or normal hepatocytes.
The findings revealed that 98 patients exhibited low EGFL6 expression, while 162 patients displayed high EGFL6 expression. We explored the associations between cytoplasmic EGFL6 expression and the clinicopathological features of HCC. Decreased cytoplasmic EGFL6 expression exhibited significant correlations with worse cellular differentiation, higher T classification, vascular invasion, higher stage, and tumor recurrence. Survival analyses, using Kaplan-Meier survival curves for HCC patients, revealed that those with reduced cytoplasmic EGFL6 expression experienced significantly worse disease-free survival (DFS) and disease-specific survival (DSS). Univariate and multivariate analyses identified EGFL6 as an independent predictor for decreased expression, differentiation grade, vascular invasion, stage, or recurrence in cases of DFS or DSS in HCC.
This study represents, to the best of our knowledge, the first investigation into the expression of EGFL6 protein in HCC. Taken together, our findings strongly suggest that EGFL6 likely plays a crucial role in the pathogenesis of HCC and indicates that targeting EGFL6 could be a promising therapeutic strategy.
背景/目的：肝细胞癌（HCC）是最常见的原发性肝癌，也是全球癌症相关死亡的第二大主要原因。本研究旨在探讨表皮生长因子样结构域 6（EGFL6）在 HCC 中的表达的临床相关性，并评估 EGFL6 在 HCC 中的表达是否具有诊断和预后意义。
本研究旨在使用免疫组织化学分析检测 260 例 HCC 组织标本中的 EGFL6 蛋白表达水平。免疫组织化学研究显示非肿瘤或正常肝细胞的细胞质中存在强烈的 EGFL6 表达。
发现 98 例患者 EGFL6 表达低，而 162 例患者 EGFL6 表达高。我们探讨了细胞质 EGFL6 表达与 HCC 临床病理特征之间的关联。细胞质 EGFL6 表达降低与细胞分化差、T 分级高、血管侵犯、分期高和肿瘤复发显著相关。对 HCC 患者进行 Kaplan-Meier 生存曲线的生存分析显示，细胞质 EGFL6 表达降低的患者无病生存（DFS）和疾病特异性生存（DSS）明显较差。单因素和多因素分析均表明，EGFL6 是 DFS 或 DSS 中表达降低、分化程度、血管侵犯、分期或复发的独立预测因子。
就我们所知，这是首次研究 EGFL6 蛋白在 HCC 中的表达。综上所述，我们的研究结果强烈表明 EGFL6 可能在 HCC 的发病机制中发挥重要作用，并表明靶向 EGFL6 可能是一种有前途的治疗策略。
