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无赖氨酸激酶1(WNK赖氨酸缺陷蛋白激酶1)的异常表达与结肠腺癌的不良预后相关。

Aberrant expression of WNK lysine deficient protein kinase 1 is associated with poor prognosis of colon adenocarcinoma.

作者信息

Jiang Huiyuan, Cheng Xin, Liang Yanjie, Wang Yan, Li Yiqun, Li Yaoping

机构信息

Department of Colorectal & Anal Surgery, Affiliated Tumor Hospital of Shanxi Medical University, Taiyuan, China.

Department of Gynecology, First Affiliated Hospital of Shanxi Medical University, Taiyuan, China.

出版信息

Ir J Med Sci. 2023 Feb;192(1):57-64. doi: 10.1007/s11845-021-02916-5. Epub 2022 Feb 9.

Abstract

BACKGROUNDS

WNK1 (WNK lysine deficient protein kinase 1) is a kind of protein kinase and participates in angiogenesis, having a potent tumor promoting role. WNK1 is ubiquitously expressed, and its upregulated expression has been reported in several tumor types.

AIMS

Here, we aimed to investigate the correlation between WNK1 expression and colon adenocarcinoma (COAD) progression.

METHODS

In the current study, WNK1 expression was evaluated by immunohistochemically in adjacent normal colonic mucosae and primary adenocarcinomas. The effect of WNK1 on overall survival (OS) and its associations with the clinicopathological parameters were analyzed in a retrospective cohort of COAD patients (n = 185). The tumor-related effects of WNK1 in COAD were further tested via cellular and mice experiments.

RESULTS

According to our cohort, higher WNK1 expression was significantly associated with unfavorable prognostic factors, such as high pT stage, pN stage, as well as shorter OS. Moreover, WNK1 exhibited tumor promoting role in COAD cancer cell lines as well as in nude mice. Silencing WNK1 can significantly inhibit the proliferation of COAD both in vitro and in vivo.

CONCLUSIONS

In all, WNK1 acts as a tumor promoter and may be used as a COAD prognostic biomarker.

摘要

背景

WNK1(赖氨酸缺陷型蛋白激酶1)是一种蛋白激酶,参与血管生成,具有强大的肿瘤促进作用。WNK1广泛表达,其表达上调已在多种肿瘤类型中被报道。

目的

在此,我们旨在研究WNK1表达与结肠腺癌(COAD)进展之间的相关性。

方法

在本研究中,通过免疫组织化学法评估WNK1在相邻正常结肠黏膜和原发性腺癌中的表达。在一组COAD患者(n = 185)的回顾性队列中分析WNK1对总生存期(OS)的影响及其与临床病理参数的关联。通过细胞和小鼠实验进一步测试WNK1在COAD中的肿瘤相关作用。

结果

根据我们的队列研究,较高的WNK1表达与不良预后因素显著相关,如高pT分期、pN分期以及较短的OS。此外,WNK1在COAD癌细胞系以及裸鼠中均表现出肿瘤促进作用。沉默WNK1可在体外和体内显著抑制COAD的增殖。

结论

总之,WNK1作为一种肿瘤促进因子,可能用作COAD的预后生物标志物。

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