Ma Xiao-Lu, Tang Wei-Guo, Yang Min-Jie, Xie Su-Hong, Wu Min-Le, Lin Guo, Lu Ren-Quan
Department of Clinical Laboratory, Shanghai Cancer Center, Fudan University, Shanghai, China.
Department of Oncology, Shanghai Medical School, Fudan University, Shanghai, China.
Front Oncol. 2020 Apr 30;10:511. doi: 10.3389/fonc.2020.00511. eCollection 2020.
Previous studies reported that stress-induced phosphoprotein 1 (STIP1) can be secreted by hepatocellular carcinoma (HCC) cells and is increased in the serum of HCC patients. However, the therapy-monitoring and prognostic value of serum STIP1 in HCC remains unclear. Here, we aimed to systemically explore the prognostic significance of serum STIP1 in HCC. A total of 340 HCC patients were recruited to this study; 161 underwent curative resection and 179 underwent transcatheter arterial chemoembolization (TACE). Serum STIP1 was detected by enzyme-linked immunosorbent assay (ELISA). Optimal cutoff values for serum STIP1 in resection and TACE groups were determined by receiver operating characteristic (ROC) analysis. Prognostic value was assessed by Kaplan-Meier, log-rank, and Cox regression analyses. Predictive values of STIP1 for objective response (OR) to TACE and MVI were evaluated by ROC curves and logistic regression. Serum STIP1 was significantly increased in HCC patients when compared with chronic hepatitis B patients or health donors (both < 0.05). Optimal cutoff values for STIP1 in resection and TACE groups were 83.43 and 112.06 ng/ml, respectively. High pretreatment STIP1 was identified as an independent prognosticator. Dynamic changes in high STIP1 status were significantly associated with long-term prognosis, regardless of treatment approaches. Moreover, post-TACE STIP1 was identified as an independent predictor for OR, with a higher area under ROC curve (AUC-ROC) than other clinicopathological features. Specifically, pretreatment STIP1 was significantly increased in patients with microvascular invasion (MVI), and was confirmed as a novel, powerful predictor for MVI. Serum STIP1 is a promising biomarker for outcome evaluation, therapeutic response assessment, and MVI prediction in HCC. Integration serum STIP1 detection into HCC management might facilitate early clinical decision making to improve the prognosis of HCC.
既往研究报道，应激诱导磷蛋白1（STIP1）可由肝细胞癌（HCC）细胞分泌，且在HCC患者血清中升高。然而，血清STIP1在HCC中的治疗监测及预后价值仍不明确。在此，我们旨在系统探讨血清STIP1在HCC中的预后意义。本研究共纳入340例HCC患者；其中161例行根治性切除术，179例行经动脉化疗栓塞术（TACE）。采用酶联免疫吸附测定（ELISA）法检测血清STIP1。通过受试者工作特征（ROC）分析确定切除组和TACE组血清STIP1的最佳临界值。采用Kaplan-Meier法、对数秩检验和Cox回归分析评估预后价值。通过ROC曲线和逻辑回归评估STIP1对TACE客观缓解率（OR）及微血管侵犯（MVI）的预测价值。与慢性乙型肝炎患者或健康供者相比，HCC患者血清STIP1显著升高（均P<0.05）。切除组和TACE组STIP1的最佳临界值分别为83.43和112.06 ng/ml。术前STIP1水平高被确定为独立预后因素。无论治疗方式如何，高STIP1状态的动态变化与长期预后显著相关。此外，TACE术后STIP1被确定为OR的独立预测因素，其ROC曲线下面积（AUC-ROC）高于其他临床病理特征。具体而言，微血管侵犯（MVI）患者术前STIP1显著升高，并被确认为MVI的新型有力预测因素。血清STIP1是HCC预后评估、治疗反应评估及MVI预测的有前景的生物标志物。将血清STIP1检测纳入HCC管理可能有助于早期临床决策，改善HCC患者预后。
