Ha Sang Yun, Song Dae Hyun, Hwang Soo Hyun, Cho Soo Youn, Park Cheol-Keun
Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Hepatobiliary Pancreat Dis Int. 2015 Apr;14(2):171-7. doi: 10.1016/s1499-3872(14)60326-x.
Prothymosin alpha (PTMA) is a nuclear oncoprotein-transcription factor essential for cell cycle progression and proliferation. PTMA was overexpressed in several human malignancies including hepatocellular carcinoma (HCC). However, the prognostic significance of PTMA protein expression in HCC remains unclear. In the present study, we evaluated PTMA protein expression by immunohistochemistry in order to elucidate the prognostic roles of PTMA in HCC patients.
By immunohistochemistry, we investigated the expression of PTMA protein in tumor tissue from 226 HCC patients who underwent curative hepatectomy. Univariate and multivariate analyses were performed to evaluate its predictive value for tumor recurrence and survival of patients. The median follow-up period was 120 months.
PTMA expression was observed in 162 (71.7%) of the 226 HCC patients and was significantly associated with higher Edmondson grade, microvascular invasion, intrahepatic metastasis, higher American Joint Committee on Cancer (AJCC) T-stage, and lower albumin level. PTMA expression was an independent predictor of early recurrence (P=0.001). PTMA expression showed an unfavorable influence on recurrence-free survival (RFS) (P<0.001). Subgroup analysis showed that among patients with tumor size ≤5.0 cm (140 patients), patients at AJCC T-stage 1 (95 patients) and patients with alpha-fetoprotein ≤20 ng/mL (83 patients), the differences in RFS between PTMA-positive and PTMA-negative groups were also statistically significant (P=0.017, P=0.002 and P=0.002, respectively). In addition, PTMA expression was an independent predictor of shorter RFS (P=0.011). PTMA expression showed an unfavorable influence on overall survival (P=0.014), but was not an independent predictor of shorter overall survival (P=0.161).
PTMA protein expression might be a novel predictor of early recurrence and RFS in HCC patients, even those at early stage or with alpha-fetoprotein-negative after curative hepatectomy. PTMA could be used as an immunohistochemical biomarker to detect patients with a high risk of recurrence.
前胸腺素α（PTMA）是一种核癌蛋白转录因子，对细胞周期进程和增殖至关重要。PTMA在包括肝细胞癌（HCC）在内的多种人类恶性肿瘤中过表达。然而，PTMA蛋白表达在HCC中的预后意义仍不明确。在本研究中，我们通过免疫组织化学评估PTMA蛋白表达，以阐明PTMA在HCC患者中的预后作用。
通过免疫组织化学，我们研究了226例行根治性肝切除术的HCC患者肿瘤组织中PTMA蛋白的表达。进行单因素和多因素分析以评估其对患者肿瘤复发和生存的预测价值。中位随访期为120个月。
226例HCC患者中有162例（71.7%）观察到PTMA表达，且与较高的Edmondson分级、微血管侵犯、肝内转移、较高的美国癌症联合委员会（AJCC）T分期及较低的白蛋白水平显著相关。PTMA表达是早期复发的独立预测因素（P=0.001）。PTMA表达对无复发生存期（RFS）有不利影响（P<0.001）。亚组分析显示，在肿瘤大小≤5.0 cm的患者（140例）、AJCC T分期为1期的患者（95例）及甲胎蛋白≤20 ng/mL的患者（83例）中，PTMA阳性组和PTMA阴性组之间的RFS差异也具有统计学意义（分别为P=0.017、P=0.002和P=0.002）。此外，PTMA表达是RFS较短的独立预测因素（P=0.011）。PTMA表达对总生存期有不利影响（P=0.014），但不是总生存期较短的独立预测因素（P=0.161）。
PTMA蛋白表达可能是HCC患者早期复发和RFS的新型预测指标，即使是根治性肝切除术后处于早期或甲胎蛋白阴性的患者。PTMA可作为一种免疫组化生物标志物用于检测复发高危患者。
