Abstract
Breast cancer (BC) is a common malignant tumor in females around the world. While multimodality therapies exist, the mortality rate remains high. The hypoxic condition was one of the potent determinants in BC progression. The molecular mechanisms underpinning hypoxia and their association with BC can contribute to a better understanding of tailored therapies. In this study, two hypoxic induced BC transcriptomic cohorts (GSE27813 and GSE47533) were assessed from the GEO database. The P4HA1 gene was identified as a putative candidate and significantly regulated in hypoxic BC cells compared to normal BC cells at different time intervals (6 h, 9 h, 16 h, 32 h, and 48 h). In patients with Luminal (p < 1E-12), triple-negative subclasses (p = 1.35059E-10), Stage 1 (p = 8.8817E-16), lymph node N1 (p = 1.62436E-12), and in the 40–80 age group (p = 1.62447E-12), the expression of P4HA1 was closely associated with the clinical subtypes of BC. Furthermore, at the 10q22.1 chromosomal band, the P4HA1 gene displayed a high copy number elevation and was associated with a poor clinical regimen with overall survival, relapse-free survival, and distant metastases-free survival in BC patients. In addition, using BioGRID, the protein–protein interaction (PPI) network was built and the cellular metabolic processes, and hedgehog pathways are functionally enriched with GO and KEGG terms. This tentative result provides insight into the molecular function of the P4HA1 gene, which is likely to promote hypoxic-mediated carcinogenesis, which may favor early detection of BC and therapeutic stratification.
Highlights
The second leading cause of tumor-related death worldwide is breast cancer (BC) (WCRF, 2018)
A differential transcriptional level of P4HA1 between Breast cancer (BC) and paired normal breast tissue was evaluated by the UALCAN database to determine the mRNA expression of P4HA1 in BC patients
P4HA1 expression was analyzed with the metastatic lymph node classification and elevated level of expression in N1 (p = 1.62436E-12) than N0 (p ≤ 1E-12)
Summary
The second leading cause of tumor-related death worldwide is breast cancer (BC) (WCRF, 2018). Molecular heterogeneity in BC inter-/intra-tumor increases tumor growth and becomes more complex in therapy (Koren and Bentires-Alj, 2015; Haynes et al, 2017)A common trait of cancer cells is that they quickly proliferate, consuming significant amounts of oxygen that hampers the low-level oxygen. Multi-Omics Analysis in Breast Cancer state called hypoxia. The hypoxia-inducible factor 1 (HIF-1) regulator pathway gets activated once the cancer cell enters hypoxic conditions (1–5% O2), contributing to the promotion of angiogenesis and metastatic tumor characteristics in BC (Murugesan and Premkumar, 2018; Al Tameemi et al, 2019; Dillekas et al, 2019). Almost 90% of BC deaths are reported due to delayed late diagnosis (Dillekas et al, 2019). HIF-1 was implicated in hematogenous breast metastases to lung cancer and was associated with low patient survival and resistance to chemotherapy in breast (Campbell et al, 2019), gastric (Cheng et al, 2012), and colorectal (Baba et al, 2010) cancer
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