Cancer Surgery and Metabolism Research Group, University of Sydney, Kolling Institute of Medical Research, St Leonards, NSW, Australia.
Upper GI Surgical Unit, Royal North Shore Hospital and North Shore Private Hospital, St Leonards, NSW, Australia; Discipline of Surgery, The University of Sydney, Camperdown, NSW, Australia.
J Surg Res. 2019 Jun;238:127-136. doi: 10.1016/j.jss.2019.01.008. Epub 2019 Feb 13.
Hepatocellular carcinoma (HCC) is a common cause of cancer death worldwide. Resection offers the best chance of long-term survival, but a consistent adverse prognostic factor is the presence of microvascular invasion (MVI). In this study, surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS), a high throughput method of analyzing complex samples, was used to explore differentially expressed proteins between HCC and adjacent nontumour liver tissue (ANLT). These findings were correlated with clinical outcomes.
From 2002 to 2011, tumor and ANLT were collected from patients who underwent liver resection and these samples were later prepared for SELDI-TOF MS. Output data were then used to identify proteins capable of discriminating HCC from ANLT. Proteins from the multivariate analysis were then analyzed to determine prognostic factors and the m/z ratios of these proteins were entered into the ExPASy database to infer potential candidates.
During the study period, 30 patients had SELDI-TOF MS performed on their HCC and ANLT samples. On multivariate analysis, a panel of four proteins-m/z 5840, m/z 8921, m/z 9961, and m/z 25,872-discriminated HCC from ANLT with an area under the ROC curve of 0.954 (P < 0.001). On prognostic factor assessment, decreased m/z 9961 was significantly associated with the presence of MVI (P = 0.025) and shorter disease-free survival (P = 0.045) in our patients. A potential candidate for this protein was coxsackievirus and adenovirus receptor, isoform 3 (CAR 3/7), which helps maintain tight junction integrity.
Using SELDI TOF-MS, we identified a panel of four proteins with excellent discriminative capacity between HCC and ANLT. Of these, m/z 9961 was the only protein significantly associated with a known poor prognostic factor (presence of MVI) and survival (shorter disease-free survival). While loss of CAR 3/7 could lead to MVI, further research is warranted to validate the identity of protein m/z 9961.
肝细胞癌（HCC）是全球癌症死亡的常见原因。切除是长期生存的最佳机会，但一致的不利预后因素是存在微血管侵犯（MVI）。在这项研究中，表面增强激光解吸/电离飞行时间质谱（SELDI-TOF MS），一种分析复杂样本的高通量方法，用于探索 HCC 与相邻非肿瘤肝组织（ANLT）之间差异表达的蛋白质。这些发现与临床结果相关。
2002 年至 2011 年，从接受肝切除术的患者中收集肿瘤和 ANLT 组织，并随后对这些样本进行 SELDI-TOF MS 准备。然后使用输出数据来识别能够区分 HCC 与 ANLT 的蛋白质。对多变量分析中的蛋白质进行分析，以确定预后因素，并将这些蛋白质的 m/z 比值输入 ExPASy 数据库以推断潜在候选物。
在研究期间，对 30 例 HCC 和 ANLT 样本进行了 SELDI-TOF MS 检测。在多变量分析中，一组四个蛋白质-m/z 5840、m/z 8921、m/z 9961 和 m/z 25872-区分 HCC 与 ANLT 的 ROC 曲线下面积为 0.954（P <0.001）。在预后因素评估中，m/z 9961 的减少与我们患者中 MVI 的存在（P = 0.025）和无病生存期（DFS）较短（P = 0.045）显著相关。该蛋白的一个潜在候选物是柯萨奇病毒和腺病毒受体，同种型 3（CAR 3/7），它有助于维持紧密连接的完整性。
使用 SELDI TOF-MS，我们鉴定了一组四个在 HCC 和 ANLT 之间具有出色区分能力的蛋白质。在这些蛋白质中，m/z 9961 是唯一与已知不良预后因素（MVI 存在）和生存（DFS 较短）显著相关的蛋白质。虽然 CAR 3/7 的丢失可能导致 MVI，但需要进一步研究来验证蛋白质 m/z 9961 的身份。
