Ye Ling, Lin Sheng-Tao, Mi Yu-Shuai, Liu Yuan, Ma Yang, Sun Hui-Min, Peng Zhi-Hai, Fan Jun-Wei
Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Pathology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Tumour Biol. 2016 Nov;37(11):14585-14594. doi: 10.1007/s13277-016-5332-3. Epub 2016 Sep 10.
This study investigated the significance of La-related protein 1 (LARP1) in the development and progression of colorectal cancer (CRC). Quantitative real-time polymerase chain reaction and Western blot analyses were carried out to determine the mRNA and protein expression of LARP1 in CRC tumor tissues and paired adjacent normal mucosa. The expression of LARP1 was upregulated in CRC. Immunohistochemical analysis using tissue microarray was performed. A positive correlation between LARP1 and proliferating cell nuclear antigen (PCNA) in the area of proliferation was observed using the Spearman's correlation coefficient test (r = 0.332, P < 0.01). The elevated expression of LARP1 significantly correlated with T stage (P = 0.02), N stage (P = 0.006), M stage (P < 0.001), American Joint Committee on Cancer (AJCC) stage (P = 0.04), differentiation rank (P < 0.001), and PCNA level (P < 0.001). In addition, the inhibitory effect of LARP1 knockdown on CRC cell proliferation was demonstrated using Cell Counting Kit-8 (CCK8) and colony-forming cell (CFC) assays. Multivariate analysis showed that LARP1 was an independent prognostic factor for overall survival (OS; hazard rate (HR) = 0.244; 95 % confidence interval (CI), 0.078-0.769; P = 0.016) and disease-free survival (DFS; HR = 0.281; 95 % CI, 0.086-0.917; P = 0.035) in CRC patients. LARP1 plays an important role in the proliferation of colorectal cancer and represents a new prognostic indicator.
本研究调查了La相关蛋白1（LARP1）在结直肠癌（CRC）发生发展过程中的意义。采用定量实时聚合酶链反应和蛋白质免疫印迹分析，以确定LARP1在CRC肿瘤组织及配对的相邻正常黏膜中的mRNA和蛋白表达。LARP1在CRC中表达上调。利用组织芯片进行免疫组织化学分析。采用Spearman相关系数检验观察到在增殖区域LARP1与增殖细胞核抗原（PCNA）之间呈正相关（r = 0.332，P < 0.01）。LARP1表达升高与T分期（P = 0.02）、N分期（P = 0.006）、M分期（P < 0.001）、美国癌症联合委员会（AJCC）分期（P = 0.04）、分化等级（P < 0.001）及PCNA水平（P < 0.001）显著相关。此外，使用细胞计数试剂盒-8（CCK8）和集落形成细胞（CFC）试验证明了敲低LARP1对CRC细胞增殖的抑制作用。多因素分析表明，LARP1是CRC患者总生存期（OS；风险比（HR）= 0.244；95%置信区间（CI），0.078 - 0.769；P = 0.016）和无病生存期（DFS；HR = 0.281；95%CI，0.086 - 0.917；P = 0.035）的独立预后因素。LARP1在结直肠癌增殖中起重要作用，是一种新的预后指标。
