In Silico Identification of Genes Associated with Breast Cancer Progression and Prognosis and Novel Therapeutic Targets

Abstract

Molecular mechanisms underlying breast cancer (BC) progression are complex and remain unclear. In this study, we used bioinformatic tools to identify genes associated with tumor progression mechanisms and novel therapeutic targets in BC. We identified genes with stepwise upregulated expression overlapping between the T and N stages during BC progression using LinkedOmics. We compared the expression level of each gene in BC tissues with that in normal breast tissues and evaluated differences in expression in their intrinsic subtypes and their prognostic value using UALCAN and GEPIA2. We also investigated the dependency of BC cell lines on these genes and whether they are potential therapeutic targets using DepMap. SPDEF, TRIM3, ABCB9, HSPB1, RHBG, SPINT1, EPN3, LRFN2, and PRPH were found to be involved in BC progression. High expression of ABCB9 and SPINT1 was associated with a poor prognosis. SPDEF, TRIM3, ABCB9, RHBG, SPINT1, and PRPH were found to be essential for survival in some BC cell lines (gene effect score < −0.5). PRPH was newly discovered to be involved in the progression of BC and the growth and survival of BC cell lines. Hence, SPDEF, TRIM3, ABCB9, RHBG, SPINT1, and PRPH may serve as novel potential therapeutic targets in BC.

Pharmacokinetics and drug-likeness of anticancer phytoconstituents: ADMET, Molecular docking, and Simulation studies

“…Disease development is also influenced by a number of other factors, such as environmental and lifestyle impacts (Criscitiello and Corti 2022). There are several other genes known to be involved in breast cancer progression like TRIM3, ABCB9, SPDEF, HSPB1, RHBG, SPINT1, EPN3, LRFN2, PRPH, etc (Uchida et al 2022). SPDEF (Sam pointed domain containing ETS transcription factor) is a prostate-derived ETS factor that maintains homeostasis, and differentiation of epithelial tissues, and heritable alterations in cancer.…”

State-of-the-Art Cancer Biology, Biodiagnostics and Therapeutics in Japan

“…Next, Kawashita et al revealed that the degree of radiation-induced mucositis can be predicted on the basis of patient lymphocyte counts at the pre-radiation stage [5]. Other studies focusing on individual cancer types are included in this Special Edition, with research on breast cancer [6], renal cell carcinoma [7,8], ovarian cancer from ovarian endometrioma [9], and inflammatory bowel disease (IBD), conditions which sometimes transform into cancer-prone phenotype [10]. Breast cancer is the most commonly diagnosed cancer in women, and Uchida et al identified the nine candidate genes constituting therapeutic targets of breast cancer using existing databases.…”

“…Breast cancer is the most commonly diagnosed cancer in women, and Uchida et al identified the nine candidate genes constituting therapeutic targets of breast cancer using existing databases. These were RNA-seq-based expression profiles taken from breast cancer tissues and CRISPR-Cas9/RNAi-based dependency maps of genes based upon the survival rate of cell lines derived from breast cancer tissue [6]. Clear cell renal cell carcinoma (ccRCC) is dominant in kidney cancer, the mortality rate for which has recently increased worldwide.…”