Ma Gang, Li Qianjun, Dai Weijie, Yang Xiaozhong, Sang Aiyu
Department of Gastroenterology, Huai'an First People's Hospital, Nanjing Medical University, 6 Beijing Road West, Huai'an, Jiangsu, 223300, People's Republic of China.
Department of Internal Medicine, Lianshui Third People's Hospital, 12 Gaogouzhen 307 Road South, Lianshui, Jiangsu, 223411, People's Republic of China.
Pathol Oncol Res. 2017 Oct;23(4):899-905. doi: 10.1007/s12253-017-0282-7. Epub 2017 Aug 9.
The microRNA (miR)-302 family consisting four members, miR-302a, miR-302b, miR-302c and miR-302d, plays an important role in diverse biological processes, and regulates many pathological changes, including cancer. However, the involvement of the miR-302 family into human gastric cancer (GC) remains unclear. The aim of this study was to investigate the expression patterns of miR-302a/b/c/d and determine their clinical significance in GC.
Expression levels of miR-302a/b/c/d in 160 pairs of human GC and matched normal mucosa tissues were detected by quantitative real-time polymerase chain reaction. Then, the associations of miR-302a/b/c/d expression with various clinicopathological characteristics and patients' prognosis were statistically evaluated.
The expression levels of miR-302a, miR-302b and miR-302c in GC tissues were all significantly lower than those in matched normal mucosa (all P < 0.001), but miR-302d expression had no significant differences between cancer and normal groups. Additionally, GC patients with low miR-302a, miR-302b and miR-302c expression more frequently had positive lymph node metastasis (all P < 0.05), advanced TNM stage (all P < 0.05) and great depth of invasion (all P < 0.05). More importantly, low miR-302a, miR-302b and miR-302c expression in GC tissues were significantly associated with shorter disease-free and overall survivals of GC patients (all P < 0.05). Further multivariate analysis identified miR-302a, miR-302b and miR-302c as independent prognostic markers for GC patients.
GC patients with the decreased expression of miR-302a, miR-302b and miR-302c may had aggressive cancer progression and unfavorable prognosis. Further rigorous validation based on a large cohort of clinical cases should be performed.
由四个成员（miR-302a、miR-302b、miR-302c和miR-302d）组成的微小RNA（miR）-302家族在多种生物学过程中发挥重要作用，并调节包括癌症在内的许多病理变化。然而，miR-302家族在人类胃癌（GC）中的作用仍不清楚。本研究旨在探讨miR-302a/b/c/d的表达模式，并确定它们在GC中的临床意义。
采用定量实时聚合酶链反应检测160对人GC组织及配对正常黏膜组织中miR-302a/b/c/d的表达水平。然后，对miR-302a/b/c/d表达与各种临床病理特征及患者预后的相关性进行统计学评估。
GC组织中miR-302a、miR-302b和miR-302c的表达水平均显著低于配对的正常黏膜组织（均P < 0.001），但miR-302d在癌症组和正常组之间的表达无显著差异。此外，miR-302a、miR-302b和miR-302c低表达的GC患者更常出现阳性淋巴结转移（均P < 0.05）、晚期TNM分期（均P < 0.05）和侵袭深度大（均P < 0.05）。更重要的是，GC组织中miR-302a、miR-302b和miR-302c低表达与GC患者较短的无病生存期和总生存期显著相关（均P < 0.05）。进一步的多因素分析确定miR-302a、miR-302b和miR-302c为GC患者的独立预后标志物。
miR-302a、miR-302b和miR-302c表达降低的GC患者可能具有侵袭性的癌症进展和不良预后。应基于大量临床病例进行进一步严格验证。
