Liu Xin-Rui, Cai Cui-Xia, Luo Li-Min, Zheng Wen-Ling, Shi Rong, Zeng Jun, Xu You-Qin, Wei Min, Ma Wen-Li
Institute of Genetic Engineering, School of Basic Medical Sciences, Southern Medical University, No.1838, Baiyun Road North, Guangzhou, China.
Centre for Liver Disease, 458th Hospital of PLA, Guangzhou, 510602 China.
Cancer Cell Int. 2016 Feb 29;16:15. doi: 10.1186/s12935-016-0286-5. eCollection 2016.
Sushi Domain Containing 2 (SUSD2) has been identified as a regulator of colon and breast cancer. Increasing evidence suggests that SUSD2 plays a key role in tumorigenesis. However, the SUSD2 expression status and its functions in hepatocellular carcinoma (HCC) are still unrevealed. In the present study, we intended to investigate SUSD2 expression status and its correlation with the clinicopathological features in HCC patients. Furthermore,we examined the influence of SUSD2 on the proliferation, apoptosis, invasion and migration of the HCC cell lines HepG2 and SMMC7721.
We evaluated the SUSD2 expression in HCC tissues and paired normal liver tissues by quantitative real-time PCR and western blotting analysis. The clinicopathological significance of SUSD2 was investigated by immunohistochemistry (IHC) on a HCC tissue microarray. Receiver operating characteristic (ROC) analysis was applied to determine the optimal cut-off score for positive expression of SUSD2. The correlation between SUSD2 protein expression and clinicopathological features of HCC was analyzed by Chi square test. The cell proliferation, apoptosis, invasion and migration potential were observed to detect the functions of SUSD2 in HCC cells.
Decreased expression of SUSD2 mRNA and protein were observed in the majority of HCC tissues, compared with paired normal liver tissues. When SUSD2 high expression percentage was determined to be above 52.5 % (area under ROC curve = 0.769, P = 0.000), low expression of SUSD2 was observed in 62.2 % (112/180) of HCC tissues and high expression of SUSD2 was observed in all normal liver tissues (16/16) by IHC. Decreased expression of SUSD2 in patients was correlated with high histological grade (χ(2) = 5.198, P = 0.023), advanced clinical stage (χ(2) = 30.244, P = 0.000), pT status (χ(2) = 33.175, P = 0.000), pN status (χ(2) = 4.785, P = 0.029), pM status (χ(2) = 4.620, P = 0.032). Down-regulation of SUSD2 promoted cell proliferation,invasion and migration,reduced the cell apoptosis.
Our findings suggest that SUSD2 may play as a tumor suppressor in HCC cells and could be served as an additional potential marker for diagnosis.
含寿司结构域蛋白2（SUSD2）已被确定为结肠癌和乳腺癌的一种调节因子。越来越多的证据表明，SUSD2在肿瘤发生过程中起关键作用。然而，SUSD2在肝细胞癌（HCC）中的表达状态及其功能仍不清楚。在本研究中，我们旨在调查HCC患者中SUSD2的表达状态及其与临床病理特征的相关性。此外，我们研究了SUSD2对HCC细胞系HepG2和SMMC7721增殖、凋亡、侵袭和迁移的影响。
我们通过定量实时PCR和蛋白质印迹分析评估HCC组织及配对正常肝组织中SUSD2的表达。通过对HCC组织芯片进行免疫组织化学（IHC）检测来研究SUSD2的临床病理意义。应用受试者工作特征（ROC）分析来确定SUSD2阳性表达的最佳截断分数。通过卡方检验分析SUSD2蛋白表达与HCC临床病理特征之间的相关性。观察细胞增殖、凋亡、侵袭和迁移潜能，以检测SUSD2在HCC细胞中的功能。
与配对的正常肝组织相比，大多数HCC组织中观察到SUSD2 mRNA和蛋白表达降低。当将SUSD2高表达百分比确定为高于52.5%（ROC曲线下面积=0.769，P=0.000）时，通过IHC在62.2%（112/180）的HCC组织中观察到SUSD2低表达，而在所有正常肝组织（16/16）中观察到SUSD2高表达。患者中SUSD2表达降低与高组织学分级（χ²=5.198，P=0.023）、临床晚期（χ²=30.244，P=0.000）、pT状态（χ²=33.175，P=0.000）、pN状态（χ²=4.785，P=0.029）、pM状态（χ²=4.620，P=0.032）相关。SUSD2的下调促进细胞增殖、侵袭和迁移，减少细胞凋亡。
我们的研究结果表明，SUSD2可能在HCC细胞中起肿瘤抑制作用，并且可作为一种额外的潜在诊断标志物。
