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CENPL mRNA 的过表达可能受 miR-340-3p 调控，可预测胰腺癌患者的预后。

Overexpression of CENPL mRNA potentially regulated by miR-340-3p predicts the prognosis of pancreatic cancer patients.

机构信息

Department of Hepatobiliary Disease, 900th Hospital of the Joint Logistics Support Force (Dongfang Hospital), Xiamen University, Fuzhou, 350025, Fujian, China.

Department of Gastroenterology, the Fourth Affiliated Hospital (Liuzhou Workers' Hospital), Guangxi Medical University, Liuzhou, 545000, Guangxi, China.

出版信息

BMC Cancer. 2022 Dec 26;22(1):1354. doi: 10.1186/s12885-022-10450-5.

DOI:10.1186/s12885-022-10450-5

PMID:36572856

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9793567/

Abstract

BACKGROUND

In our previous study it was found that CENPL was overexpressed in hepatocellular carcinoma and significantly predicted patient's prognosis. However, the expression and prognostic value of CENPL in other gastrointestinal tumors remain unknown. Therefore, we investigated the expression and prognostic value of CENPL in esophageal carcinoma (ESCA), stomach adenocarcinoma (STAD), pancreatic adenocarcinoma (PAAD), colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ).

METHODS

In this study, Oncomine, GEPIA, OncoLnc, TIMER, cBioPortal, miRWalk and ENCORI databases were used to analyze the level of CENPL mRNA, prognostic value and potential regulatory mechanism of CENPL mRNA in tumors. The CENPL expression and clinicopathological data regarding PAAD were from the UCSC Xena database and univariate and multivariate Cox regression analyses were performed using R (Version 3.6.3). Immunohistochemical staining was used to verify the expression of CENPL protein in clinical specimens. Cytoscape (Version: 3.7.2) was used to visualize microRNA (miRNA) that potentially regulates CENPL.

RESULTS

Gene differential expression analysis showed that CENPL mRNA was significantly overexpressed in ESCA, STAD, PAAD, COAD and READ (p < 0.01). The overexpression of CENPL mRNA was significantly correlated with the poor prognosis of PAAD patients (p < 0.05). However, there was no significant correlation between the level of CENPL mRNA and the prognosis of ESCA, STAD, COAD and READ patients (p > 0.05). Univariate and multivariate Cox regression analyses suggested that CENPL was a prognostic risk factor for PAAD. The mutation rate of CENPL in PAAD was 2.2% (17/850). There was no significant correlation between the CENPL expression and the infiltration levels of immune cells in PAAD (|Cor|< 0.5). Immunohistochemical staining showed that CENPL was overexpressed in 42% (11/26) of PAAD specimens, which was significantly higher compared with that in the normal tissues. The expression of miR-340-3p and miR-484 in PAAD were significantly lower than in the normal tissues (p < 0.05) and PAAD patients with lower expression of miR-340-3p had poorer prognosis (p < 0.05).

CONCLUSION

CENPL potentially regulated by miR-340-3p, is overexpressed in PAAD and predicts patient's prognosis, suggestive of a diagnostic and prognostic value in PAAD patients.

摘要

背景

在我们之前的研究中发现，CENPL 在肝细胞癌中过表达，并显著预测了患者的预后。然而，CENPL 在其他胃肠道肿瘤中的表达和预后价值尚不清楚。因此，我们研究了 CENPL 在食管鳞癌（ESCA）、胃腺癌（STAD）、胰腺导管腺癌（PAAD）、结肠腺癌（COAD）和直肠腺癌（READ）中的表达和预后价值。

方法

本研究利用 Oncomine、GEPIA、OncoLnc、TIMER、cBioPortal、miRWalk 和 ENCORI 数据库分析了 CENPL mRNA 的水平、预后价值以及 CENPL mRNA 在肿瘤中的潜在调控机制。PAAD 中 CENPL 的表达和临床病理数据来自 UCSC Xena 数据库，采用 R（版本 3.6.3）进行单变量和多变量 Cox 回归分析。免疫组织化学染色用于验证临床标本中 CENPL 蛋白的表达。Cytoscape（版本：3.7.2）用于可视化潜在调节 CENPL 的微小 RNA（miRNA）。

结果

基因差异表达分析表明，CENPL mRNA 在 ESCA、STAD、PAAD、COAD 和 READ 中均显著过表达（p<0.01）。CENPL mRNA 的过表达与 PAAD 患者的不良预后显著相关（p<0.05）。然而，CENPL mRNA 的水平与 ESCA、STAD、COAD 和 READ 患者的预后之间没有显著相关性（p>0.05）。单变量和多变量 Cox 回归分析表明，CENPL 是 PAAD 的预后危险因素。PAAD 中 CENPL 的突变率为 2.2%（17/850）。CENPL 的表达与 PAAD 中免疫细胞浸润水平之间没有显著相关性（|Cor|<0.5）。免疫组织化学染色显示，在 42%（11/26）的 PAAD 标本中 CENPL 过表达，明显高于正常组织。PAAD 中 miR-340-3p 和 miR-484 的表达明显低于正常组织（p<0.05），miR-340-3p 表达较低的 PAAD 患者预后较差（p<0.05）。