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细胞骨架基因改变与肝癌索拉非尼耐药相关。

Cytoskeletal gene alterations linked to sorafenib resistance in hepatocellular carcinoma.

机构信息

Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Hainan, China.

Department of Pharmacy, Peking University Third Hospital, 49 Huayuan North Rd, Haidian District, Beijing, 100191, China.

出版信息

World J Surg Oncol. 2024 Jun 7;22(1):152. doi: 10.1186/s12957-024-03417-2.

DOI:10.1186/s12957-024-03417-2
PMID:38849867
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11157844/
Abstract

BACKGROUND

Although sorafenib has been consistently used as a first-line treatment for advanced hepatocellular carcinoma (HCC), most patients will develop resistance, and the mechanism of resistance to sorafenib needs further study.

METHODS

Using KAS-seq technology, we obtained the ssDNA profiles within the whole genome range of SMMC-7721 cells treated with sorafenib for differential analysis. We then intersected the differential genes obtained from the analysis of hepatocellular carcinoma patients in GSE109211 who were ineffective and effective with sorafenib treatment, constructed a PPI network, and obtained hub genes. We then analyzed the relationship between the expression of these genes and the prognosis of hepatocellular carcinoma patients.

RESULTS

In this study, we identified 7 hub ERGs (ACTB, CFL1, ACTG1, ACTN1, WDR1, TAGLN2, HSPA8) related to drug resistance, and these genes are associated with the cytoskeleton.

CONCLUSIONS

The cytoskeleton is associated with sorafenib resistance in hepatocellular carcinoma. Using KAS-seq to analyze the early changes in tumor cells treated with drugs is feasible for studying the drug resistance of tumors, which provides reference significance for future research.

摘要

背景

尽管索拉非尼一直被用作晚期肝细胞癌（HCC）的一线治疗药物，但大多数患者会产生耐药性，需要进一步研究索拉非尼耐药的机制。

方法

使用 KAS-seq 技术，我们获得了索拉非尼处理的 SMMC-7721 细胞全基因组范围内的 ssDNA 图谱，用于差异分析。然后，我们将从 GSE109211 中分析对索拉非尼治疗无效和有效的肝细胞癌患者中获得的差异基因进行交集，构建 PPI 网络，并获得枢纽基因。然后，我们分析了这些基因的表达与肝细胞癌患者预后之间的关系。

结果

在这项研究中，我们确定了 7 个与耐药相关的 ERGs（ACTB、CFL1、ACTG1、ACTN1、WDR1、TAGLN2、HSPA8），这些基因与细胞骨架有关。

结论

细胞骨架与肝细胞癌对索拉非尼的耐药性有关。使用 KAS-seq 分析药物处理后的肿瘤细胞的早期变化，对于研究肿瘤的耐药性是可行的，为未来的研究提供了参考意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b9/11157844/5fa787a1a6af/12957_2024_3417_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b9/11157844/f1be29429c71/12957_2024_3417_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b9/11157844/6a89bb09b740/12957_2024_3417_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b9/11157844/eb075466ad4a/12957_2024_3417_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b9/11157844/38a6902d2917/12957_2024_3417_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b9/11157844/7be3c7e9168e/12957_2024_3417_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b9/11157844/a2898d12c44b/12957_2024_3417_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b9/11157844/b63c94a82ae8/12957_2024_3417_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b9/11157844/d600ecae06cc/12957_2024_3417_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b9/11157844/5fa787a1a6af/12957_2024_3417_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b9/11157844/f1be29429c71/12957_2024_3417_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b9/11157844/6a89bb09b740/12957_2024_3417_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b9/11157844/eb075466ad4a/12957_2024_3417_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b9/11157844/38a6902d2917/12957_2024_3417_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b9/11157844/7be3c7e9168e/12957_2024_3417_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b9/11157844/a2898d12c44b/12957_2024_3417_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b9/11157844/b63c94a82ae8/12957_2024_3417_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b9/11157844/d600ecae06cc/12957_2024_3417_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12b9/11157844/5fa787a1a6af/12957_2024_3417_Fig9_HTML.jpg

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