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Abstract
Breast cancer is the most common cancer among women globally. In India, the incidence of breast cancer has increased significantly during the last two decades with a higher proportion of the disease at a young age compared to the west. To understand the molecular processes underlying breast cancer in Indian women, we analysed gene expression profiles of 29 tumours and 9 controls using microarray. In the present study, we obtained 2413 differentially expressed genes, consisting of overexpressed genes such as COL10A1, COL11A1, MMP1, MMP13, MMP11, GJB2, and CST1 and underexpressed genes such as PLIN1, FABP4, LIPE, AQP7, LEP, ADH1A, ADH1B, and CIDEC. The deregulated pathways include cell cycle, focal adhesion and metastasis, DNA replication, PPAR signaling, and lipid metabolism. Using PAM50 classifier, we demonstrated the existence of molecular subtypes in Indian women. In addition, qPCR validation of expression of metalloproteinase genes, MMP1, MMP3, MMP11, MMP13, MMP14, ADAMTS1, and ADAMTS5 showed concordance with that of the microarray data; wherein we found a significant association of ADAMTS5 down-regulation with older age (≥55 years) of patients. Together, this study reports gene expression profiles of breast tumours from the Indian subcontinent, throwing light on the pathways and genes associated with the breast tumourigenesis in Indian women.
Highlights
Breast cancer is the most common cancer among women worldwide, representing nearly a quarter (25%) of all cancers with an estimated 2.1 million new cancer cases diagnosed in 20181
Molecular subtyping based on expression of estrogen receptor (ER), progesterone receptor (PR), and HER2/neu, yielded 33 cases (42.85%) to luminal subtype, 17 (22.07%) cases to basal subtype, and 23 cases (29.87%) to HER2/neu overexpressing subtype (Supplementary Table S2), and for 4 cases (5.19%) molecular subtype could not be determined as the expression of ER, PR and HER2/neu were not available for these cases
Volcano plots were drawn to get an overview of differential gene expression among different tumour groups (Fig. 1); it was observed that the proportion of down-regulated genes were more than up-regulated genes in Total tumours (TT), Early-onset tumours (ET), and Late-onset tumours (LT) tumour groups
Summary
Breast cancer is the most common cancer among women worldwide, representing nearly a quarter (25%) of all cancers with an estimated 2.1 million new cancer cases diagnosed in 20181. Over the past two decades, there has been a rapid increase in breast cancer incidence throughout Asia, mainly South-Eastern Asia, including India[2,3,4,5,6]. An incidence rate of 45.5% has been observed in Asian countries for this age group, suggesting a higher incidence of breast cancer in the younger age group in India and other Asian countries as compared to the western population[8]. There is a single report describing gene expression profiles of breast cancer from Indian patients, focusing mainly on estrogen receptor (ER) positive and ER-negative tumours profiles alone[11]. We have analysed the gene signatures and molecular pathways involved in breast carcinogenesis in Indian women by transcriptome profiling
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