Integrative analysis of autophagy-related genes reveals that CAPNS1 is a novel prognostic biomarker and promotes the malignancy of melanoma via Notch signaling pathway.

IF 3.6 3区 医学 Q2 ONCOLOGY
American journal of cancer research Pub Date : 2024-08-25 eCollection Date: 2024-01-01 DOI:10.62347/ECDF2762
Mengru Gao, Jisong Liu, Miaomiao Yang, Xiangzhou Zhang, Yulian Zhang, Zhuliang Zhou, Jiabin Deng
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引用次数: 0

Abstract

Skin cutaneous melanoma (SKCM) is a highly fatal form of skin cancer that develops from the malignant transformation of epidermal melanocytes. There is substantial evidence linking autophagy to cancer etiology and immunotherapy efficacy. This study aimed to conduct a comprehensive analysis of autophagy-related genes (ARGs) using TCGA datasets and further explore the potential function of critical ARGs in SKCM progression. We performed comprehensive bioinformatics analysis uses the TCGA dataset. RT-PCR was applied to examine the expression of CAPNS1 in SKCM cells. Lost-of-function experiments were performed to detect the expression of the related proteins. In this search, we screed 70 differentially expressed autophagy-related genes (DE-ARGs), including 33 up-DE-ARGs and 37 down-DE-ARGs. Enrichment assays revealed that these 70 DE-ARGs may exert influence on critical cellular processes such as autophagy, protein kinase activity, and signaling pathways, impacting cell growth, differentiation, survival, and tumor development. Then, we further explore the prognostic value of 70 DE-ARGs and confirmed 18 survival-related DE-ARGs in SKCM patients. Nearly all the 18 DE-ARGs' methylation was negatively correlated with their corresponding expression in SKCM. The 12 survival-related DE-ARGs were used to develop a unique predictive model that effectively classified SKCM patients into high- and low-risk groups with regard to overall survival. Furthermore, tumor environment analysis indicated that the risk score was associated with several immune cells. Among the 12 survival-related DE-ARGs, our attention focused on CAPNS1 which was highly expressed in SKCM patients and predicted a poor prognosis. In addition, we confirmed that knockdown of CAPNS1 distinctly suppressed the proliferation, metastasis and EMT of SKCM cells, and promoted autophagy via regulating Notch signaling pathway. Overall, this study enhances our understanding of the intricate molecular landscape of SKCM progression and presents promising avenues for future research and clinical applications.

对自噬相关基因的整合分析表明,CAPNS1是一种新的预后生物标志物,它通过Notch信号通路促进黑色素瘤的恶性发展。
皮肤黑色素瘤(SKCM)是一种高度致命的皮肤癌,由表皮黑色素细胞恶性转化而成。有大量证据表明,自噬与癌症病因学和免疫疗法的疗效有关。本研究旨在利用TCGA数据集对自噬相关基因(ARGs)进行全面分析,并进一步探索关键ARGs在SKCM进展过程中的潜在功能。我们利用TCGA数据集进行了全面的生物信息学分析。我们应用 RT-PCR 技术检测了 CAPNS1 在 SKCM 细胞中的表达。我们还进行了功能缺失实验,以检测相关蛋白的表达。在这次搜索中,我们筛选出了 70 个差异表达的自噬相关基因(DE-ARGs),包括 33 个上调表达的 DE-ARGs 和 37 个下调表达的 DE-ARGs。富集试验显示,这70个DE-ARGs可能对自噬、蛋白激酶活性和信号通路等关键细胞过程产生影响,从而影响细胞的生长、分化、存活和肿瘤发生。随后,我们进一步探讨了70个DE-ARGs的预后价值,并在SKCM患者中证实了18个与生存相关的DE-ARGs。在 SKCM 中,几乎所有 18 个 DE-ARGs 的甲基化都与其相应的表达呈负相关。利用这12个与生存相关的DE-ARGs建立了一个独特的预测模型,该模型能有效地将SKCM患者的总生存期分为高危和低危两组。此外,肿瘤环境分析表明,风险评分与几种免疫细胞有关。在 12 个与生存相关的 DE-ARGs 中,我们关注的重点是 CAPNS1,它在 SKCM 患者中高表达,预示着不良预后。此外,我们还证实,敲除 CAPNS1 能明显抑制 SKCM 细胞的增殖、转移和 EMT,并通过调节 Notch 信号通路促进自噬。总之,这项研究加深了我们对 SKCM 进展过程中错综复杂的分子图谱的理解,并为未来的研究和临床应用提供了前景广阔的途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
自引率
3.80%
发文量
263
期刊介绍: The American Journal of Cancer Research (AJCR) (ISSN 2156-6976), is an independent open access, online only journal to facilitate rapid dissemination of novel discoveries in basic science and treatment of cancer. It was founded by a group of scientists for cancer research and clinical academic oncologists from around the world, who are devoted to the promotion and advancement of our understanding of the cancer and its treatment. The scope of AJCR is intended to encompass that of multi-disciplinary researchers from any scientific discipline where the primary focus of the research is to increase and integrate knowledge about etiology and molecular mechanisms of carcinogenesis with the ultimate aim of advancing the cure and prevention of this increasingly devastating disease. To achieve these aims AJCR will publish review articles, original articles and new techniques in cancer research and therapy. It will also publish hypothesis, case reports and letter to the editor. Unlike most other open access online journals, AJCR will keep most of the traditional features of paper print that we are all familiar with, such as continuous volume, issue numbers, as well as continuous page numbers to retain our comfortable familiarity towards an academic journal.
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