Jyothi Vennela, Pottakkat Biju, V Balasubramaniyan, Verma Surendra Kumar
Surgical Gastroenterology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, IND.
Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, IND.
Cureus. 2023 Aug 21;15(8):e43844. doi: 10.7759/cureus.43844. eCollection 2023 Aug.
Angiogenesis plays a vital role in the progression of hepatocellular carcinoma (HCC) by contributing to tumor growth and metastasis. Netrin-4 (NTN4) is a secreted glycoprotein that regulates angiogenesis and maintains endothelial homeostasis. There were no studies found focusing on the value of NTN4 as a serum biomarker for the diagnosis and prognosis of HCC. In this study, we aimed to investigate the systemic expression of NTN4 in patients with HCC. We also explore the association of NTN4 with major clinicopathological and biochemical characteristics of HCC.
A total of 116 patients with HCC and 44 healthy volunteers were recruited in this case-control study. Clinical characteristics and liver function parameters were recorded among the study subjects. The levels of α-fetoprotein (AFP) were quantified in patients with HCC. The serum levels of NTN4 (pg/ml) were estimated by enzyme-linked immunosorbent assay (ELISA).
The median NTN4 levels were significantly decreased in patients with HCC when compared to control subjects (p < 0.0001). There was no difference between NTN4 levels in AFP-positive patients and AFP-negative patients (p = 0.39). Of note, NTN4 levels were significantly decreased in HCC patients with metastasis (p < 0.02) and portal vein invasion (p < 0.04). Further, NTN4 levels were significantly reduced in HCC patients with Child-Pugh C score (p < 0.05). The receiver operating characteristic curve for serum levels of NTN4 in the HCC group and control group was generated. At a cut-off of 30 pg/ml, the sensitivity and specificity for NTN4 were 80% and 82%, respectively, with an AUC of 0.894.
Low levels of NTN4 were associated with increased tumor aggressiveness and metastasis in HCC. Estimation of circulating NTN4 has prognostic value as a minimally invasive biomarker in HCC. Future studies might shed the role of NTN4 in the development of HCC.
血管生成通过促进肿瘤生长和转移在肝细胞癌（HCC）进展中起重要作用。Netrin-4（NTN4）是一种分泌型糖蛋白，可调节血管生成并维持内皮细胞稳态。尚未发现有研究关注NTN4作为HCC诊断和预后血清生物标志物的价值。在本研究中，我们旨在调查HCC患者中NTN4的全身表达情况。我们还探讨了NTN4与HCC主要临床病理和生化特征的相关性。
本病例对照研究共纳入116例HCC患者和44名健康志愿者。记录研究对象的临床特征和肝功能参数。对HCC患者的甲胎蛋白（AFP）水平进行定量检测。采用酶联免疫吸附测定（ELISA）法评估血清NTN4水平（pg/ml）。
与对照组相比，HCC患者的NTN4水平中位数显著降低（p < 0.0001）。AFP阳性患者和AFP阴性患者的NTN4水平无差异（p = 0.39）。值得注意的是，发生转移（p < 0.02）和门静脉侵犯（p < 0.04）的HCC患者NTN4水平显著降低。此外，Child-Pugh C级评分的HCC患者NTN4水平显著降低（p < 0.05）。绘制了HCC组和对照组血清NTN4水平的受试者工作特征曲线。在截断值为30 pg/ml时，NTN4的敏感性和特异性分别为80%和82%，曲线下面积为0.894。
低水平的NTN4与HCC中肿瘤侵袭性增加和转移相关。循环NTN4的评估作为HCC的一种微创生物标志物具有预后价值。未来的研究可能会阐明NTN4在HCC发生发展中的作用。
