Integrated analysis of expression profiling data identifies three genes in correlation with poor prognosis of triple-negative breast cancer

Abstract

Triple-negative breast cancer (TNBC) shows more aggressive clinical behavior and poorer outcome than non-triple-negative breast cancer (NTNBC), and cannot be treated either via endocrine therapy or by Trastuzumab. For TNBC, chemotherapy is currently the mainstay of systemic medical treatment, the lack of more efficient options of treatment has been a problem in breast cancer prevention. In this study, we aimed to find genes related to prognosis in TNBC by bioinformatic analysis and to provide therapeutic candidates for TNBC treatment. We compared the differences in gene expression levels between cancer patients and healthy individuals across five breast cancer microarray databases to generate a gene cohort specifically upregulated in the NTNBC subtype, whose expression levels are ≥2-fold higher in TNBC compared to NTNBC and healthy individuals. Another two databases with clinical information were applied for following Kaplan-Meier analysis, and high expression of BIRC5, CENPA and FAM64A in this cohort were found to be related to poor survival (OS, DMFS, DFS and RFS). This correlation was also seen in patients at early stages and grades. On the other hand, the outcome of patients with synchronous upregulation of these three genes was the worst, while those with synchronous low gene level was the best. In conclusion, BIRC5, CENPA and FAM64A are specifically upregulated in TNBC, and the high expression of these three genes is associated with poor breast cancer prognosis, suggesting their clinical implication as therapeutic targets in TNBC.

Transcriptional response profiles of paired tumor-normal samples offer novel perspectives in pan-cancer analysis

“…FAM64A and TROAP were selected based on the following five criteria: (1) they were rarely reported in previous researches; (2) they have been detected in tumor tissues; (3) their functions in cancer progression are still unclear; (4) they belong to cell cycle related genes and other genes, respectively; (5) their proportions of samples with log2(fold-change) ≥ 2 in all 633 samples ranked at the top in all the genes satisfying criteria (1-4). Among cell cycle related genes, FAM64A was reported only in five papers and one paper reported its association with poor prognosis of triple-negative breast cancer [43]. Among other genes, TROAP was reported only in four papers and one paper reported its detection in serous ovarian adenocarcinoma [44].…”

Associating transcriptional modules with colon cancer survival through weighted gene co-expression network analysis

“…This gene is implicated in cell cycle and mitotic pathways; the GO annotations of this gene include protein heterodimerisation activity and chromatin binding. CENPA is also a potential prognostic biomarker of breast cancer, and the increased expression of this gene is associated with the poor survival of breast cancer patients [27, 28]. Among various core markers in neoplasic intratubullar germ cells, such as CD9, CENPA and PODXL, CENPA is overexpressed, and this finding suggests that this gene may be a potential biological marker of human diseases [29].…”

Elevated expression of the centromere protein‐A(CENP‐A)‐encoding gene as a prognostic and predictive biomarker in human cancers

“…There is a critical need for prognostic and predictive biomarkers in oncology. To date, elevated CENP‐A expression in breast and ovarian cancer patients has been associated with poor patient survival . In the present study, we have investigated whether elevated expression of CENP‐A could be used as a prognostic and predictive factor in a variety of human cancers.…”