Abstract
Invasive ductal breast carcinoma (IDBC) is the most prevalent type of invasive breast cancer in females; however, the pathogenesis of IDBC remains to be elucidated. Therefore, the identification of novel markers may enhance current understanding of the initiation and development of IDBC as well as elucidate potential therapeutic targets for effective treatment of IDBC. In the present study, a pilot study was conducted to screen for potential mRNAs and long non-coding (lnc)RNAs that exhibit aberrantly altered expression in patients with IDBC. Fresh breast cancer specimens and normal breast tissues were obtained from three female patients with IDBC aged ≥60 years following a modified radical mastectomy without chemotherapy. Expression levels of 44,244 probes were detected and included in the analysis, of which 22,078 (49.9%) were mRNAs and 22,166 (50.1%) were lncRNAs. Potential marker screening was performed using paired t-tests (criterion 1), false discovery rates (FDR; criterion 2) and sure independence screening procedures based on distance correlations (DC-SIS; criterion 3). The results showed that in IDBC tissues 3,510 probes had a ≥2-fold statistically significant change in expression levels compared to those in the corresponding normal breast tissue (P<0.05); in addition, following FDR analysis, 353 probes were found to have significantly altered expression levels. Furthermore, DC-SIS analysis identified 18 probes (12 mRNA and 6 lncRNAs) with significantly altered expression levels in IDBC tissue; these 18 probes therefore demonstrated significant results in all three criteria. Several of the mRNAs identified have been previously reported to be involved in signal transduction, protein binding, and cancer pathways, and the present study revealed that the majority of their gene products were located in the cytoplasm. Two of the six identified lncRNAs demonstrated a >10-fold decrease in expression levels in IDBC tissues compared to that in the normal breast tissue. However, further studies are required in order to elucidate the biological functions of the identified probes.
Highlights
Breast cancer is the most prevalent type of malignant cancer in females worldwide, of which invasive ductal breast carcinoma (IDBC), known as infiltrating ductal carcinoma, accounts for 70‐80% of invasive breast cancer cases [1]
A previous study identified a paracrine network between tumor and stromal cells comprising of CXCL1 and 2, which indicated that lung metastasis was associated with chemotherapy resistance in breast cancer [25]
Another mRNA identified in the present study, A_33_P3290338, is found in the PARP1 gene, which encodes a nuclear enzyme that has an important role in regulating DNA repair [26]
Summary
Breast cancer is the most prevalent type of malignant cancer in females worldwide, of which invasive ductal breast carcinoma (IDBC), known as infiltrating ductal carcinoma, accounts for 70‐80% of invasive breast cancer cases [1]. It was reported that an interim stage, DCIS with microinvasion, may have an important role in the progression from DCIS to metastatic IDBC [5]. This linear multi‐step model of human breast cancer progression serves as a starting point for current understanding of breast cancer pathogenesis; numerous studies have contradicted this model [4,6]. A previous study into the transcriptomic landscape of breast cancer using in‐depth mRNA sequencing revealed numerous novel and annotated transcripts in breast cancer tissue; this reflected the limited current understating of mRNAs in the pathogenesis of the disease [8]
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