MAPK8IP2 是前列腺癌中一个有潜力的预后生物标志物和促进肿瘤进展的因素。

MAPK8IP2 is a potential prognostic biomarker and promote tumor progression in prostate cancer.

机构信息

Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, 330000, China.

Jiangxi Institute of Urology, Nanchang, 330000, China.

出版信息

BMC Cancer. 2022 Nov 11;22(1):1162. doi: 10.1186/s12885-022-10259-2.

DOI:10.1186/s12885-022-10259-2

PMID:36357836

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9650804/

Abstract

BACKGROUND

MAPK8IP2 is one of the JNK-interacting proteins (JIPs) family members, and is involved in the regulation of the JNK and P38 MAPK signaling pathways. MAPK8IP2 has been reported to be closely associated with several cancers. However, the biological function of MAPK8IP2 in prostate cancer (PCa) remains unclear.

METHODS

MAPK8IP2 expression in PCa and subgroups of PCa was analyzed by public databases. The prognostic role of MAPK8IP2 in prostate cancer was analyzed using the Cox regression method. The potential mechanism by which MAPK8IP2 affects PCa progression was investigated by utilizing public data, including genetic alteration, DNA methylation, m6A methylation, and immune infiltration data. We further performed in vitro assays to validate the effect of MAPK8IP2 on PCa cell proliferation, migration and invasion.

RESULTS

MAPK8IP2 is highly expressed in PCa tissues. Overexpression of MAPK8IP2 is associated with adverse clinicopathological factors and a poor prognosis in PCa. Receiver operating curve analysis showed that MAPK8IP2 can distinguish PCa tissues from non-PCa tissues with a certain accuracy (AUC = 0.814). The MAPK8IP2 genetic alteration rate was 2.6% and MAPK8IP2 alterations correlated with a poor prognosis. We also found that CDK12 and TP53 mutations were associated with MAPK8IP2 expression. The DNA methylation level of MAPK8IP2 was higher in primary tumors than in normal tissues, and the high MAPK8IP2 DNA methylation group of PCa patients had poor survival. Enrichment analysis indicated that MAPK8IP2 was involved in the MAPK signaling pathway. In vitro, knockdown of MAPK8IP2 inhibited PCa cell proliferation, migration and invasion.

CONCLUSION

MAPK8IP2 is a potential target for PCa treatment and can serve as a novel biomarker for PCa diagnosis and prognosis evaluation.

摘要

背景

MAPK8IP2 是 JNK 相互作用蛋白（JIPs）家族成员之一，参与 JNK 和 P38 MAPK 信号通路的调节。已有报道称 MAPK8IP2 与多种癌症密切相关。然而，MAPK8IP2 在前列腺癌（PCa）中的生物学功能仍不清楚。

方法

通过公共数据库分析 MAPK8IP2 在 PCa 及 PCa 亚组中的表达。利用 Cox 回归方法分析 MAPK8IP2 对前列腺癌的预后作用。利用公共数据（包括遗传改变、DNA 甲基化、m6A 甲基化和免疫浸润数据）研究 MAPK8IP2 影响 PCa 进展的潜在机制。我们还进一步进行了体外实验，以验证 MAPK8IP2 对 PCa 细胞增殖、迁移和侵袭的影响。

结果

MAPK8IP2 在 PCa 组织中高表达。MAPK8IP2 的过表达与不良的临床病理因素和 PCa 的不良预后相关。ROC 曲线分析显示，MAPK8IP2 可以一定程度上区分 PCa 组织和非 PCa 组织（AUC=0.814）。MAPK8IP2 的遗传改变率为 2.6%，MAPK8IP2 的改变与预后不良相关。我们还发现 CDK12 和 TP53 突变与 MAPK8IP2 表达相关。MAPK8IP2 的 DNA 甲基化水平在原发性肿瘤中高于正常组织，MAPK8IP2 DNA 甲基化水平高的 PCa 患者生存不良。富集分析表明，MAPK8IP2 参与了 MAPK 信号通路。在体外，MAPK8IP2 的敲低抑制了 PCa 细胞的增殖、迁移和侵袭。