Zhan Xiao-Yong, Zhang Yaqiong, Zhai Ertao, Zhu Qing-Yi, He Yulong
The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Guangzhou KingMed Center for Clinical Laboratory, Guangzhou, China.
PeerJ. 2018 May 29;6:e4829. doi: 10.7717/peerj.4829. eCollection 2018.
Sorting nexin-1 (SNX1) is an important functional protein in cell endocytosis, efflux, protein sorting, cell signal transduction, etc; however, the expression, the role and clinical relevance of SNX1 have not been investigated in gastric cancer (GC). In this study, we first performed a bioinformatics investigation using the data obtained from The Cancer Genome Atlas (TCGA) database. The result showed that SNX1 mRNA levels were significantly lower in GC tissues than in paracancerous tissues. In a study of 150 cases of GC, including 60 cases with paired paracancerous and cancer tissues and 90 cases with detailed follow-up information, SNX1 expression was analyzed by immunohistochemistry. Our study on paired paracancerous and cancer tissues showed that SNX1 protein expression remarkably decreased in GC tissues (50/60, 83.33%). A study on 90 patients with detailed follow-up information showed that tumors with higher SNX1 protein level were correlated with better clinicopathologic stages ( = 0.0285), nodal status ( = 0.0286), smaller tumor sizes ( = 0.0294) and a better survival rate in patients with GC ( = 0.0245). Univariate analysis of the 90 patients with GC showed that low-level SNX1 was significantly correlated with decreased overall survival of GC patients ( = 0.008), and associated with a relatively higher cumulative hazard of death. Exogenous expression of SNX1 inhibited the growth, migration, invasion and promoted the apoptosis and enhanced the sensitivity of GC cells to the chemotherapeutic drug 5-Fluorouracil (5-Fu) in vitro, while knockdown of SNX1 by short hairpin RNA (shRNA) significantly promoted the growth, migration, invasion and reduced the apoptosis and the sensitivity of GC cells to 5-Fu. SNX1 also showed to influence the levels of epithelial-mesenchymal transition markers including Vimentin, Snail, and E-cadherin in GC cells in vitro. Taken together, we propose here that SNX1 serves as a tumor suppressor and prognostic marker that reduces tumor cell malignancy for GC.
分选连接蛋白-1（SNX1）是细胞内吞作用、外排作用、蛋白质分选、细胞信号转导等过程中的一种重要功能蛋白；然而，SNX1在胃癌（GC）中的表达、作用及临床相关性尚未得到研究。在本研究中，我们首先利用从癌症基因组图谱（TCGA）数据库获得的数据进行了生物信息学研究。结果显示，GC组织中SNX1 mRNA水平显著低于癌旁组织。在一项对150例GC患者的研究中，包括60例癌旁组织与癌组织配对的患者以及90例有详细随访信息的患者，通过免疫组织化学分析了SNX1的表达。我们对癌旁组织与癌组织配对的研究表明，GC组织中SNX1蛋白表达显著降低（50/60，83.33%）。对90例有详细随访信息的患者的研究表明，SNX1蛋白水平较高的肿瘤与更好的临床病理分期（P = 0.0285）、淋巴结状态（P = 0.0286）、较小的肿瘤大小（P = 0.0294）以及GC患者更好的生存率（P = 0.0245）相关。对90例GC患者的单因素分析表明，低水平的SNX1与GC患者总生存期的降低显著相关（P = 0.008），并与相对较高的累积死亡风险相关。体外实验中，SNX1的外源性表达抑制了GC细胞的生长、迁移、侵袭，促进了细胞凋亡，并增强了GC细胞对化疗药物5-氟尿嘧啶（5-Fu）的敏感性，而短发夹RNA（shRNA）敲低SNX1则显著促进了GC细胞的生长、迁移、侵袭，降低了细胞凋亡以及GC细胞对5-Fu的敏感性。体外实验中，SNX1还显示出影响GC细胞中包括波形蛋白、Snail和E-钙黏蛋白在内的上皮-间质转化标志物的水平。综上所述，我们在此提出，SNX1作为一种肿瘤抑制因子和预后标志物，可降低GC肿瘤细胞的恶性程度。
