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Breast Cancer Research and Treatment

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08.07.2021 | Preclinical study

KMT2C is a potential biomarker of prognosis and chemotherapy sensitivity in breast cancer

verfasst von: Xinhua Liu, Rongfang Qiu, Min Xu, Miaomiao Meng, Siyu Zhao, Jiansong Ji, Yang Yang

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 2/2021

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Abstract

Purpose

Epigenetic regulation plays critical roles in cancer progression, and high-frequency mutations or expression variations in epigenetic regulators have been frequently observed in tumorigenesis, serving as biomarkers and targets for cancer therapy. Here, we aimed to explore the function of epigenetic regulators in breast cancer.

Methods

The mutational landscape of epigenetic regulators in breast cancer samples was investigated based on datasets from the Cancer Genome Atlas. The Kaplan–Meier method was used for survival analysis. RNA sequencing (RNA-seq) in MCF-7 cells transfected with control siRNA or KMT2C siRNA was performed. Quantitative reverse transcription-PCR and chromatin immunoprecipitation were used to validate the RNA-seq results.

Results

Among the 450 epigenetic regulators, KMT2C was frequently mutated in breast cancer samples. The tumor mutational burden (TMB) was elevated in breast cancer samples with KMT2C mutations or low KMT2C mRNA levels compared to their counterparts with wild-type KMT2C or high KMT2C mRNA levels. Somatic mutation and low expression of KMT2C were independently correlated with the poor overall survival (OS) and disease-free survival (DFS) of the breast cancer samples, respectively. RNA-seq analysis combined with chromatin immunoprecipitation and qRT-PCR assays revealed that the depletion of KMT2C remarkably affected the expression of DNA damage repair-related genes. More importantly, the low expression of KMT2C was related to breast cancer cell sensitivity to chemotherapy and longer OS of breast cancer patients who underwent chemotherapy.

Conclusion

We conclude that KMT2C could serve as a potential biomarker of prognosis and chemotherapy sensitivity by affecting the DNA damage repair-related genes of breast cancer.

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Titel: KMT2C is a potential biomarker of prognosis and chemotherapy sensitivity in breast cancer
verfasst von: Xinhua Liu
Rongfang Qiu
Min Xu
Miaomiao Meng
Siyu Zhao
Jiansong Ji
Yang Yang
Publikationsdatum: 08.07.2021
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 2/2021
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-021-06325-1

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

KMT2C is a potential biomarker of prognosis and chemotherapy sensitivity in breast cancer

Abstract

Purpose

Methods

Results

Conclusion

Neu im Fachgebiet Onkologie

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Update Onkologie

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

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