Abstract
TRIP-Brs, a group of transcription factors (TFs) that modulate several mechanisms in higher organisms. However, the novel paradigm to target TRIP-Brs in specific cancer remains to be deciphered. In particular, comprehensive analysis of TRIP-Brs in clinicopathological and patients’ prognosis, especially in breast cancer (BRCA), is being greatly ignored. Therefore, we explored the key roles of TRIP-Br expression, modulatory effects, mutations, immune infiltration, and prognosis in BRCA using multidimensional approaches. We found elevated levels of TRIP-Brs in numerous cancer tissues than normal. Higher expression of TRIP-Br-2/4/5 was shown to be positively associated with lower survival, tumor grade, and malignancy of patients with BRCA. Additionally, higher TRIP-Br-3/4 were also significantly linked with worse/short survival of BRCA patients. TRIP-Br-1/4/5 were significantly overexpressed and enhanced tumorigenesis in large-scale BRCA datasets. The mRNA levels of TRIP-Brs have been also correlated with tumor immune infiltrate in BRCA patients. In addition, TRIP-Brs synergistically play a pivotal role in central carbon metabolism, cancer-associated pathways, cell cycle, and thyroid hormone signaling, which evoke that TRIP-Brs may be a potential target for the therapy of BRCA. Thus, this investigation may lay a foundation for further research on TRIP-Br-mediated management of BRCA.
Highlights
Breast cancer (BRCA) is referred as the most deadly disease, and it causes approximately 6% deaths among all cancer-associated deaths worldwide.[1]
A higher expression of TRIP-Br-4 was seen in invasive breast carcinoma stroma with 2.022 mRNA levels and male breast carcinoma with fold change 1.44 that was reported by Finak et al.[32] and The Cancer Genome Atlas (TCGA) analysis
The TRIP-Brs significantly overexpressed in BRCA, kidney-carcinoma (KIRC), cholangiocarcinoma (CHOL), lung-adenocarcinoma (LUAD; except TRIP-Br-1), colon-adenocarcinoma (COAD), esophageal-carcinoma (ESCA), uterine-endometrial-carcinoma (UCEC), and lung squamous cell carcinoma (LUSC; except TRIP-Br-1), whereas significant downregulation of TRIP-Brs was observed in KICH and PRAD as compared with normal tumor tissue samples (Figures 1B–1F)
Summary
Breast cancer (BRCA) is referred as the most deadly disease, and it causes approximately 6% deaths among all cancer-associated deaths worldwide.[1]. Luminal-B: ERpositive/PRpositive/HER2positive; (3) basal-like subtypes: ERnegative/PRnegative/HER2negative/CK-5/6positive/EGFRpositive; (4) HER2overexpressing subtype: ERnegative/PRnegative/HER2positive.[3] In BRCA management, ER, PR, and HER2 have been opted as a classical prognostic biomarker that played a key function in the diagnosis and therapy of BRCA.[3,4] Despite great development in BRCA detection, treatment, and management, it has been found that around 5% to 10% of patients exhibit metastatic tumors after the first treatment, and about 1/5 of all survive 5 years.[1] Tumor heterogeneity is a common hallmark of most of cancers, including breast carcinoma.[5] Due to tumor heterogeneity, several biomarkers are suffering from limitations associated with patients’ survival and prognosis.
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