PRR11 Is a Prognostic Marker and Potential Oncogene in Patients with Gastric Cancer

PRR11 is a potential candidate oncogene that has been implicated in the pathogenesis of lung cancer, however the role of PRR11 in gastric cancer is currently unclear. In the present study, we investigated the role of PRR11 in gastric cancer by evaluating its expression status in samples from a cohort of 216 patients with gastric cancer. PRR11 was found to be overexpressed in 107 (49.5%) patients by immunohistochemistry of tissue microarrays generated using the patient samples. Furthermore, PRR11 overexpression was found to correlate significantly with clinicopathologic features such as tumor invasion, tumor differentiation, and disease stage. Survival analysis of the cohort revealed that PRR11 is an independent prognostic factor for gastric cancer patients. PRR11 was stably silenced in a gastric carcinoma cell line using an shRNA-based approach, and treated cells showed decreased cellular proliferation and colony formation in vitro and cell growth in vivo, companied by decreased expression of CTHRC1 and increased expression of LXN, proteins involved in tumor progression. Evaluation of human gastric cancer samples demonstrated that PRR11 expression was also associated with increased CTHRC1 and decreased LXN expression. These data indicate that PRR11 may be widely activated in human gastric cancer and are consistent with the hypothesis that PRR11 functions as an oncogene in the development and progression of gastric cancer.

PRR11作为一种潜在的原癌基因，其与肺癌的发病机制密切相关，然而其在胃癌中的作用目前尚不明确。本研究旨在探讨PRR11在胃癌中的功能，通过评估216例胃癌患者样本中的PRR11表达状态。通过使用患者样本构建的组织微阵列进行免疫组化检测发现，PRR11在107例（占49.5%）患者中呈过表达。此外，PRR11的过表达与临床病理特征，如肿瘤侵袭、肿瘤分化和疾病分期等显著相关。对研究队列的生存分析表明，PRR11是胃癌患者独立的不良预后因素。利用基于shRNA的沉默策略在胃癌细胞系中稳定沉默PRR11，处理后的细胞在体外表现出细胞增殖和集落形成的减少，以及体内细胞生长的抑制，伴随CTHRC1表达下降和LXN表达上升，这些蛋白与肿瘤进展密切相关。对人类胃癌样本的评估显示，PRR11的表达也与CTHRC1表达的上升和LXN表达的下降相关。这些数据表明，PRR11可能在人类胃癌中广泛激活，并与PRR11在胃癌的发生和发展过程中作为原癌基因的功能假说相一致。