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ADAMTS12作为一种新的预后生物标志物,促进胃癌的增殖和侵袭。

ADAMTS12 serves as a novel prognostic biomarker and promotes proliferation and invasion in gastric cancer.

作者信息

Gao Ruimei, Hu Yalan, Yuan Qiuxiang

机构信息

Department of Gastroenterology, Qingdao Chengyang People's Hospital, Qingdao, China.

Department of Anorectal Surgery, Qingdao Eighth People's Hospital, Qingdao, China.

出版信息

Discov Oncol. 2024 Dec 25;15(1):837. doi: 10.1007/s12672-024-01724-4.

DOI:10.1007/s12672-024-01724-4
PMID:39720953
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11669643/
Abstract

Gastric cancer (GC) remains a prevalent and aggressive malignancy with a poor prognosis. This study aimed to identify diagnostic and prognostic biomarkers while exploring their potential functions in GC. A total of 598 upregulated and 506 downregulated genes were identified in GC patients. Among these, survival-related differentially expressed genes (DEGs), including ADAMTS12, F5, and VCAN, were highlighted. Pan-cancer analyses revealed their dysregulation across multiple tumor types. A novel prognostic signature, incorporating ADAMTS12 and F5, effectively stratified GC patients into low- and high-risk groups, demonstrating significant differences in overall survival and robust predictive performance. ADAMTS12, strongly associated with advanced clinical stages and poor prognosis, was validated in an independent cohort and exhibited promising diagnostic potential. RT-PCR and western blot analyses confirmed its high expression in GC tissues and cell lines. Functional assays further demonstrated that ADAMTS12 promotes GC cell proliferation and invasion. In summary, this study provides critical insights into the molecular landscape of GC, offering a potential prognostic tool and therapeutic target.

摘要

胃癌(GC)仍然是一种常见且侵袭性强的恶性肿瘤,预后较差。本研究旨在识别诊断和预后生物标志物,同时探索它们在胃癌中的潜在功能。在胃癌患者中总共鉴定出598个上调基因和506个下调基因。其中,包括ADAMTS12、F5和VCAN在内的与生存相关的差异表达基因(DEG)受到关注。泛癌分析揭示了它们在多种肿瘤类型中的失调情况。一个包含ADAMTS12和F5的新型预后特征有效地将胃癌患者分为低风险和高风险组,在总生存期方面显示出显著差异且具有强大的预测性能。与晚期临床阶段和不良预后密切相关的ADAMTS12在一个独立队列中得到验证,并表现出有前景的诊断潜力。逆转录聚合酶链反应(RT-PCR)和蛋白质免疫印迹分析证实其在胃癌组织和细胞系中高表达。功能实验进一步证明ADAMTS12促进胃癌细胞增殖和侵袭。总之,本研究为胃癌的分子格局提供了关键见解,提供了一种潜在的预后工具和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0460/11669643/0c65af5c22c8/12672_2024_1724_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0460/11669643/f869fdc8c29e/12672_2024_1724_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0460/11669643/414a13848e4d/12672_2024_1724_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0460/11669643/fe4699a9b0f4/12672_2024_1724_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0460/11669643/36f2c8dd07cf/12672_2024_1724_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0460/11669643/7c267b40fa2d/12672_2024_1724_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0460/11669643/e5690ecf0202/12672_2024_1724_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0460/11669643/e57b28fbb307/12672_2024_1724_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0460/11669643/0c65af5c22c8/12672_2024_1724_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0460/11669643/f869fdc8c29e/12672_2024_1724_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0460/11669643/414a13848e4d/12672_2024_1724_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0460/11669643/fe4699a9b0f4/12672_2024_1724_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0460/11669643/36f2c8dd07cf/12672_2024_1724_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0460/11669643/7c267b40fa2d/12672_2024_1724_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0460/11669643/e5690ecf0202/12672_2024_1724_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0460/11669643/e57b28fbb307/12672_2024_1724_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0460/11669643/0c65af5c22c8/12672_2024_1724_Fig8_HTML.jpg

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本文引用的文献

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Genes Environ. 2024 Jan 3;46(1):1. doi: 10.1186/s41021-023-00296-z.
2
ADAMTS12 is a stromal modulator in chronic liver disease.ADAMTS12 是慢性肝病中的一种基质调节剂。
FASEB J. 2023 Nov;37(11):e23237. doi: 10.1096/fj.202200692RRRR.
3
Effects of metalloprotease ADAMTS12 on cervical cancer cell phenotype and its potential mechanism.金属蛋白酶ADAMTS12对宫颈癌细胞表型的影响及其潜在机制。
Discov Oncol. 2023 Aug 29;14(1):162. doi: 10.1007/s12672-023-00776-2.
4
Targeting cancer with mRNA-lipid nanoparticles: key considerations and future prospects.利用 mRNA-脂质纳米颗粒靶向癌症:关键考虑因素和未来前景。
Nat Rev Clin Oncol. 2023 Nov;20(11):739-754. doi: 10.1038/s41571-023-00811-9. Epub 2023 Aug 16.
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Epigenetic regulatory mechanism of ADAMTS12 expression in osteoarthritis.ADAMTS12 表达在骨关节炎中的表观遗传调控机制。
Mol Med. 2023 Jul 3;29(1):86. doi: 10.1186/s10020-023-00661-2.
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mRNA-based cancer therapeutics.mRNA 癌症疗法。
Nat Rev Cancer. 2023 Aug;23(8):526-543. doi: 10.1038/s41568-023-00586-2. Epub 2023 Jun 13.
7
Predictive biomarkers in gastric cancer.胃癌的预测生物标志物。
J Cancer Res Clin Oncol. 2023 Jan;149(1):467-481. doi: 10.1007/s00432-022-04408-0. Epub 2022 Oct 19.
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Characteristics of gastric cancer around the world.世界各地胃癌的特征。
Crit Rev Oncol Hematol. 2023 Jan;181:103841. doi: 10.1016/j.critrevonc.2022.103841. Epub 2022 Oct 11.
9
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Int J Mol Sci. 2022 Oct 2;23(19):11684. doi: 10.3390/ijms231911684.
10
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