ATP5A1的缺失促进了结肠癌的增殖,预示着结肠癌的不良预后

IF 3.2 4区 医学 Q2 PATHOLOGY
Guifeng Zhang, Jiangming Zhong, Li Lin, Zhenhua Liu
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引用次数: 1

摘要

ATP合成酶F1亚基α (ATP5F1A),也被称为ATP5A1,是线粒体ATP合成酶的一个亚基。ATP5A1表达失调已在几种恶性肿瘤中被报道,然而它在不同类型的癌症中显示出致癌或肿瘤抑制作用。本研究旨在初步探讨ATP5A1在结肠腺癌中的表达及其作用。方法我们首先利用癌症基因组图谱(TCGA)的数据评估ATP5A1的转录和mRNA水平。此外,我们在纳入的回顾性队列(n = 115)中检测了其mRNA和蛋白表达。进行单因素和多因素分析以评估其预后价值。通过细胞实验和异种移植小鼠模型验证ATP5A1在结肠癌中的作用。结果satp5a1在结肠腺癌组织中表达水平明显低于癌旁非肿瘤组织。肿瘤晚期以ATP5A1水平降低为特征。在TCGA数据集(P = 0.041)和我们的队列(P = 0.001)中,较低的ATP5A1与不良预后相关。此外,Cox回归分析显示,ATP5A1是结肠癌患者新的独立预后因素(HR=0.43, P = 0.018)。最后,细胞和异种移植数据证实,过表达ATP5A1可以显著减缓结肠癌的生长。结论ATP5A1低表达可能是结肠癌预后不良的潜在分子标志物。数据可得性数据可应要求提供。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Loss of ATP5A1 enhances proliferation and predicts poor prognosis of colon adenocarcinoma

Background

ATP Synthase F1 Subunit Alpha (ATP5F1A), also named as ATP5A1, is a subunit of mitochondrial ATP synthase. Dysregulated expression of ATP5A1 has been reported in several malignancies, nevertheless it showed either oncogenic or tumor-suppressing roles in different cancer types. Here we aimed to initially investigate the expression and role of ATP5A1 in colon adenocarcinoma.

Methods

We firstly evaluated the transcription and mRNA levels of ATP5A1 using data from The Cancer Genome Atlas (TCGA). Besides, we tested its mRNA and protein expression in our enrolled retrospective cohort (n = 115). Univariate and multivariate analyzes were conducted to assess its prognostic value. Cellular experiments and xenografts in mice model were performed to validate the role of ATP5A1 in colon cancer.

Results

ATP5A1 showed a significant lower level in colon adenocarcinoma than in adjacent nontumorous tissue. Advanced tumor stage was characterized with lower ATP5A1 level. Lower ATP5A1 was associated with poor prognosis in both TCGA dataset (P = 0.041) and our cohort (P = 0.001). Furthermore, Cox regression analysis demonstrated that ATP5A1 was a novel independent prognostic factor for colon cancer patients (HR=0.43, P = 0.018). Finally, cellular and xenografts data confirmed that overexpressing ATP5A1 can remarkably attenuate colon cancer growth.

Conclusion

Low expression of ATP5A1 may be a potential molecular marker for poor prognosis in colon cancer.

Data availability

Data will be available upon request.

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来源期刊
CiteScore
5.00
自引率
3.60%
发文量
405
审稿时长
24 days
期刊介绍: Pathology, Research and Practice provides accessible coverage of the most recent developments across the entire field of pathology: Reviews focus on recent progress in pathology, while Comments look at interesting current problems and at hypotheses for future developments in pathology. Original Papers present novel findings on all aspects of general, anatomic and molecular pathology. Rapid Communications inform readers on preliminary findings that may be relevant for further studies and need to be communicated quickly. Teaching Cases look at new aspects or special diagnostic problems of diseases and at case reports relevant for the pathologist''s practice.
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