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初探环境因素对 BRAF 突变型结直肠癌微卫星状态的影响。

Preliminary exploration of the effects of environmental factors on the microsatellite status of BRAF-mutated colorectal cancer.

机构信息

Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai, 200080, China.

Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai, 200080, China.

出版信息

World J Surg Oncol. 2023 Aug 25;21(1):264. doi: 10.1186/s12957-023-03106-6.

DOI:10.1186/s12957-023-03106-6
PMID:37620872
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10463889/
Abstract

BACKGROUND

To investigate the expression of EBV products and frequency of gallstone disease (GD) among different microsatellite status in colorectal cancer (CRC) with BRAF mutation.

METHODS

We collected 30 CRC patients with BRAF mutation and 10 BRAF ( -) CRC patients as well as 54 healthy subjects. Tumor tissue samples were collected to detect the mutation of BRAF, KRAS, and TP53. Microsatellite status was determined by immunohistochemistry and PCR. EBER in situ hybridization was performed to detect EBV. In addition, we also collected clinical information about the patients.

RESULTS

We found that although EBV products were detected in CRC, there were no significant differences in the EBV distribution between the different BRAF groups. Our study demonstrated that BRAF mutation and BRAF with MSI were significantly more frequent in the right CRC. Furthermore, the KRAS mutation rate in the BRAF-wild-type group was proved to be significantly higher than that in the BRAF mutation group. In addition, we revealed that BRAF mutation and MSI were independent risk factors of TNM stage. The frequency of GD was higher in CRC patients than in general population, and although there was no significant difference between CRC with or without BRAF mutation, the highest frequency of GD was found in MSS CRC with BRAF mutation.

CONCLUSIONS

EBV plays a role in CRC, but is not a determinant of different microsatellite status in CRC with BRAF mutation. The frequency of GD in MSS CRC with BRAF mutation is significantly higher than that in the general population.

摘要

背景

研究 BRAF 突变型结直肠癌(CRC)中不同微卫星状态下 EBV 产物的表达和胆石病(GD)的频率。

方法

我们收集了 30 例 BRAF 突变型 CRC 患者和 10 例 BRAF(-)CRC 患者以及 54 例健康对照者。采集肿瘤组织标本,检测 BRAF、KRAS 和 TP53 的突变情况。采用免疫组化和 PCR 法检测微卫星状态。采用 EBER 原位杂交法检测 EBV。此外,还收集了患者的临床资料。

结果

我们发现虽然在 CRC 中检测到 EBV 产物,但不同 BRAF 组之间 EBV 分布无显著差异。我们的研究表明,BRAF 突变和 BRAF 微卫星不稳定性(MSI)在右半 CRC 中更为常见。此外,BRAF 野生型组的 KRAS 突变率明显高于 BRAF 突变组。此外,我们揭示 BRAF 突变和 MSI 是 TNM 分期的独立危险因素。CRC 患者的 GD 发生率高于普通人群,虽然 BRAF 突变型 CRC 与无 BRAF 突变型 CRC 之间无显著差异,但 BRAF 突变型 MSS CRC 的 GD 发生率最高。

结论

EBV 在 CRC 中起作用,但不是 BRAF 突变型 CRC 中不同微卫星状态的决定因素。MSS CRC 伴 BRAF 突变的 GD 发生率明显高于普通人群。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4bd/10463889/da0faf2a6624/12957_2023_3106_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4bd/10463889/d0a4492721ab/12957_2023_3106_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4bd/10463889/1560a5081308/12957_2023_3106_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4bd/10463889/f798714474d3/12957_2023_3106_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4bd/10463889/da0faf2a6624/12957_2023_3106_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4bd/10463889/d0a4492721ab/12957_2023_3106_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4bd/10463889/1560a5081308/12957_2023_3106_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4bd/10463889/f798714474d3/12957_2023_3106_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4bd/10463889/da0faf2a6624/12957_2023_3106_Fig4_HTML.jpg

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本文引用的文献

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Combined PD-1, BRAF and MEK inhibition in BRAF colorectal cancer: a phase 2 trial.联合 PD-1、BRAF 和 MEK 抑制治疗 BRAF 结直肠癌:一项 2 期试验。
Nat Med. 2023 Feb;29(2):458-466. doi: 10.1038/s41591-022-02181-8. Epub 2023 Jan 26.
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Downregulation of ZNF280A inhibits proliferation and tumorigenicity of colorectal cancer cells by promoting the ubiquitination and degradation of RPS14.ZNF280A的下调通过促进RPS14的泛素化和降解来抑制结肠癌细胞的增殖和致瘤性。
Front Oncol. 2022 Aug 17;12:906281. doi: 10.3389/fonc.2022.906281. eCollection 2022.
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Single-Cell Sequencing and Its Applications in Liver Cancer.
单细胞测序及其在肝癌中的应用
Front Oncol. 2022 Apr 21;12:857037. doi: 10.3389/fonc.2022.857037. eCollection 2022.
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Downregulation of the farnesoid X receptor promotes colorectal tumorigenesis by facilitating enterotoxigenic Bacteroides fragilis colonization.法尼醇 X 受体下调通过促进产肠毒素脆弱拟杆菌定植促进结直肠肿瘤发生。
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Alteration in stemness causes exclusivity between Epstein-Barr virus-positivity and microsatellite instability status in gastric cancer.干性维持的改变导致胃癌中 EBV 阳性和微卫星不稳定状态之间的排他性。
Gastric Cancer. 2021 May;24(3):602-610. doi: 10.1007/s10120-020-01146-5. Epub 2021 Jan 2.
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Dietary fat, bile acid metabolism and colorectal cancer.饮食中的脂肪、胆汁酸代谢与结直肠癌。
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Reabsorption of bile acids regulated by FXR-OATP1A2 is the main factor for the formation of cholesterol gallstone.法尼醇 X 受体-OATP1A2 调控的胆汁酸重吸收是胆固醇结石形成的主要因素。
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