Based on whole-exome sequencing to explore the rule of Herceptin and TKI resistance in breast cancer patients.

Autor: Guo L; Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuhan, Hubei, 430060, People's Republic of China., Cheng H; Department of Breast Surgery, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei, 430060, People's Republic of China., Liu J; Department of breast surgery, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei Provincial Clinical Research Center for Breast Cancer, Wuhan Clinical Research Center for Breast Cancer, No.116 Zhuo Daoquan South Road, Wuhan, Hubei, 430079, People's Republic of China., Shao W; Genecast Biotechnology Co., Ltd., Wuxi, Jiangsu, 214000, People's Republic of China., Luo L; Department of Breast Surgery, The Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Road, Yunyan District, Guiyang, Guizhou, 550001, People's Republic of China., Zheng W; Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuhan, Hubei, 430060, People's Republic of China., Sun S; Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuhan, Hubei, 430060, People's Republic of China., Kong D; Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuhan, Hubei, 430060, People's Republic of China. 2016103030008@whu.edu.cn., Chen C; Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuhan, Hubei, 430060, People's Republic of China. qq332031867@163.com.
Jazyk: angličtina
Zdroj: BMC medical genomics [BMC Med Genomics] 2024 Jan 19; Vol. 17 (1), pp. 25. Date of Electronic Publication: 2024 Jan 19.
DOI: 10.1186/s12920-023-01762-x
Abstrakt: Background: Breast cancer is the second leading cause of cancer-related death in women, and drug resistance during treatment is a major challenge. However, the mechanisms underlying drug resistance are not fully understood. Here we applied whole-exome sequencing (WES) to clarify resistant rules to Herceptin and tyrosine kinase inhibitors (TKIs).
Methods: There are 12 HER2+ breast cancer patients who were done WES. Samples from tumor and surrounding tissues underwent DNA sequencing and analysis. Various experimental and bioinformatics techniques were employed, including genomic capture, mutation analysis (Genome Analysis Toolkit (GATK), etc.), bioinformatics assessments, and drug-gene interaction investigations. Ultimately, the study explored the association of APOB gene expression with breast cancer recurrence rates, immune cell infiltration, and drug response.
Results: The C > T mutation frequency was highest in the Herceptin-insensitive (HI) and verification groups, codenamed YI, contrasting with the Herceptin-sensitive (HE) group. No microsatellite instability (MSI)-H patients were in the HE group, but both HI and YI groups had 1 each. Significant differences in transition-transversion (TiTv) were observed in the HI and YI groups rather than the HE group. In the TKI- insensitive (TI) group, C > T mutations were highest, differing from the TKI-sensitive (TE) group. TE group included 2 MSI-H patients. Significant differences in TiTv were found in the TI group rather than the TE group. Mutated APOB may resist Herceptin and TKI, increasing immune infiltration. We identified potential drugs targeting it.
Conclusions: Our study suggested that a higher percentage of C > T mutations, significant differences in TiTv, and MSI-H status may indicate Herceptin resistance, while a higher percentage of C > T mutations, significant differences in TiTv, and the absence of MSI-H may indicate TKI resistance in breast cancer patients. For patients resistant to both Herceptin and TKI, mutated APOB may play a crucial role in resistance.
(© 2024. The Author(s).)
Databáze: MEDLINE
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