The overexpression of DNA repair genes in invasive ductal and lobular breast carcinomas: Insights on individual variations and precision medicine.

Ruwaa I Mohamed,Nurcan Tuncbag,Alaa S Ahmed,Eman Badr,Menattallah Elserafy,Salma A Bargal,Iman El-Shiekh,Asmaa S Mekawy,Suhwan Chang

doi:10.1371/journal.pone.0247837

Ruwaa I Mohamed, Nurcan Tuncbag + Show 7 more

Open Access

https://doi.org/10.1371/journal.pone.0247837

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Abstract

In the era of precision medicine, analyzing the transcriptomic profile of patients is essential to tailor the appropriate therapy. In this study, we explored transcriptional differences between two invasive breast cancer subtypes; infiltrating ductal carcinoma (IDC) and lobular carcinoma (LC) using RNA-Seq data deposited in the TCGA-BRCA project. We revealed 3854 differentially expressed genes between normal ductal tissues and IDC. In addition, IDC to LC comparison resulted in 663 differentially expressed genes. We then focused on DNA repair genes because of their known effects on patients’ response to therapy and resistance. We here report that 36 DNA repair genes are overexpressed in a significant number of both IDC and LC patients’ samples. Despite the upregulation in a significant number of samples, we observed a noticeable variation in the expression levels of the repair genes across patients of the same cancer subtype. The same trend is valid for the expression of miRNAs, where remarkable variations between patients’ samples of the same cancer subtype are also observed. These individual variations could lie behind the differential response of patients to treatment. The future of cancer diagnostics and therapy will inevitably depend on high-throughput genomic and transcriptomic data analysis. However, we propose that performing analysis on individual patients rather than a big set of patients’ samples will be necessary to ensure that the best treatment is determined, and therapy resistance is reduced.

Highlights

MethodsBoth RNA sequencing (RNA-seq) and microRNA sequencing (miRNA-seq) data were retrieved from The Cancer Genome Atlas—Breast Invasive Carcinoma (TCGA-BRCA) project (accession date: March 05, 2020) in the format of HTSeq-Counts for RNA-seq and BCGSC miRNA Profiling text files for miRNA-seq
Breast cancer is the most frequent cancer in women and the second most common cancer overall
Our data indicate that lobular carcinoma (LC) and infiltrating ductal carcinoma (IDC) have different transcriptomic profiles, while they express DNA repair genes in a more similar manner

Summary

Methods

Both RNA sequencing (RNA-seq) and microRNA sequencing (miRNA-seq) data were retrieved from The Cancer Genome Atlas—Breast Invasive Carcinoma (TCGA-BRCA) project (accession date: March 05, 2020) in the format of HTSeq-Counts for RNA-seq and BCGSC miRNA Profiling text files for miRNA-seq. The focus of this study is on females with ductal and lobular neoplasms. We further selected the cases with either invasive ductal carcinoma (IDC) or lobular carcinoma (LC) using the clinical datasheet of the TCGA-BRCA project. The 964 cases contributed 1,063 RNA-seq samples (89 normal_ductal, 771 IDC, and 203 LC) and 1,044 miRNA-seq samples (82 normal_ductal, 760 IDC, and 202 LC). Note that 7 RNA-seq and 6 miRNA-seq normal lobular samples were excluded because of the small sample size.

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