Zhao Qiang, Miao Congxiu, Lu Qingpu, Wu Weipeng, He Yuan, Wang Mengzhu, Liu Huimin, Zhao Jiangman, Lian Changhong
Department of Gastrointestinal Surgery, Heping Hospital, Changzhi Medical College, Changzhi, Shanxi, China.
Department of Science and Technology, Changzhi Medical College, Changzhi, Shanxi, China.
Medicine (Baltimore). 2024 Nov 22;103(47):e40601. doi: 10.1097/MD.0000000000040601.
Gastric cancer (GC) is one of the most prevalent malignant tumors in the world and has an extremely poor prognosis. Regulator of calcineurin 1 (RCAN1), a known tumor suppressor in various cancers, has an undefined role in the proliferation and metastasis of GC. Primary tumor and paired normal gastric tissues were collected from 77 patients with GC for evaluating the mRNA levels of 3 RCAN1 transcripts. Kaplan-Meier survival curves and Cox regression analysis were used to assess the prognostic value of 3 RCAN1 transcripts, and to select variables for nomogram. The mRNA levels of RCAN1 isoform 1 (RCAN1.1, P = .0312) and isoform 2 (RCAN1.2, P = .007) were significantly diminished in GC tissues compared with normal tissues, whereas isoform 4 (RCAN1.4) expression level showed no significant differences. GC patients with lower RCAN1.4 mRNA levels had shorter overall survival time than patients whose tumors had high RCAN1.4 levels (P = .04). Downregulated expression of RCAN1.4 was found to be an independent prognostic factor of overall survival in GC patients, with a hazard ratio of 2.485 and a significant P-value of .023 in multivariate Cox analysis. The concordance index of nomogram to predict overall survival was 0.788, based on RCAN1.4 level, tumor stage and lymph node metastasis status. In conclusion, our findings suggest that RCAN1.4 is a novel prognostic marker for gastric cancer, targeting RCAN1.4 may provide a promising therapeutic strategy in GC management.
胃癌(GC)是世界上最常见的恶性肿瘤之一,预后极差。钙调神经磷酸酶调节因子1(RCAN1)是各种癌症中已知的肿瘤抑制因子,在GC的增殖和转移中作用尚不明确。收集77例GC患者的原发性肿瘤组织及配对的正常胃组织,以评估3种RCAN1转录本的mRNA水平。采用Kaplan-Meier生存曲线和Cox回归分析评估3种RCAN1转录本的预后价值,并为列线图选择变量。与正常组织相比,GC组织中RCAN1亚型1(RCAN1.1,P = 0.0312)和亚型2(RCAN1.2,P = 0.007)的mRNA水平显著降低,而亚型4(RCAN1.4)的表达水平无显著差异。RCAN1.4 mRNA水平较低的GC患者总生存时间短于肿瘤RCAN1.4水平高的患者(P = 0.04)。发现RCAN1.4表达下调是GC患者总生存的独立预后因素,多因素Cox分析中风险比为2.485,P值为0.023,具有统计学意义。基于RCAN1.4水平、肿瘤分期和淋巴结转移状态的列线图预测总生存的一致性指数为0.788。总之,我们的研究结果表明,RCAN1.4是一种新的胃癌预后标志物,靶向RCAN1.4可能为GC治疗提供一种有前景的治疗策略。