Hypoxia-inducible factor 1-alpha expression correlates with response to neoadjuvant chemotherapy in women with breast cancer

Abstract

Hypoxia-inducible factor 1-alpha (HIF-1a) has been shown to contribute to resistance to chemotherapy in breast cancer. The purpose of this study was to investigate whether HIF-1a is predictive for pathological response and the prognostic value of HIF-1a in local advanced breast undergoing neoadjuvant chemotherapy.Two hundred twenty patients with none-metastatic locally advanced invasive breast cancer (stages II–III) that subsequently received neoadjuvant chemotherapy were included in an observational study to assess the HIF-1a protein expression by immunohistochemistry. Associations between HIF-1a expression and pathological complete response (pCR) were analyzed using univariate and multivariate analysis. Independent prognostic factors for RFS were identified by multivariate Cox's proportional hazard analysis. A P value < .05 was considered to be statistically significant.The median age was 46 years, Luminal A, Luminal B, HER2-positive, and triple-negative accounted for 3.6%, 57.7%, 7.0% and 16.0%, respectively. A total of 41 patients (18.6%) achieved a pCR after neoadjuvant chemotherapy in the present study. HIF-1α negative patients had a significantly higher pCR rate than HIF-1α positive patients (P = .027). Multivariate analysis demonstrated that HIF-1α negative expression is an independent favorable predictor of pCR. Multivariate Cox regression analysis demonstrated that the HIF-1a expression before NCT showed an independent prognostic value for RFS (HR = 4.168, 95% CI: 1.012–17.170, P = .048).HIF-1a expression correlates with pCR in breast cancer undergoing neoadjuvant chemotherapy. Absent expression of HIF-1a was associated with a better pathological response and could indicate a favorable prognosis in non-pCR breast cancer patients.

The plasma peptides of breast versus ovarian cancer

“…The striking agreement between the peptides and proteins observed in the plasma of breast cancer patients and the previous literature on breast cancer tumors, adjacent fluids, cell lines or blood fluids indicates that LC–ESI–MS/MS of blood peptides will be a powerful tool for selecting plasma proteins and peptides for further research and confirmation. The results of mass spectrometry show striking agreement with previous genetic or biochemical experiments on cancer tissues, tumors, biopsies or cell lines: CPEB1 [63], LTBP4 [64], HIF1A [65, 66], IGHE [67], RAB44 [68], NEFM [39], C19orf82, SLC35B1 [69], 1D12A that shows a cyptic alignment with cyclin-dependent kinase-like isoform 1 [70], C8orf34 [71], OCLN [72], EYA1 [73], HLA-DRB1 [74], LAR [75] and LRRC4B that interacts with the LARS receptor phosphatases [76], PTPDC1 [77], WWC1 [78], ZNF562, PTMA [79], MGAT1 [80], NDUFA1 [81], NOGOC [82], olfactory receptors OR1E or the HSA12 protein [83], GCSH [84], ELTD1 [85], TBX15 [86], orphan nuclear receptors such as NR2C2 [87], autophagy related proteins such as ATG16L1 (FLJ00045) that regulate the production of extracellular vesicles called exosomes [88], PDLIM1 [89, 90], GALNT9 [91], ASH2L [92], PPFIBP1 [93], SLCO3A1 [94], BHMT2 [95], CS citrate synthase [96] FAM188B2 inactive ubiquitin carboxyl-terminal hydrolase MINDY4B that is expressed in breast cancer tissue, LGALS7 [97] SAT2 [98], SFRS8, SLC22A12 [99], WNT9B [100], SLC2A4 [101], ZNF101, WT1 (Wilms Tumor Protein) [102], CCDC47 [103], ERLIN1 (SPFH1) and MREG [104], EID2 [105], THOC1 [106, 107], DDX47 [108], PTPRE [109], EMILIN1 [110], DKFZp779G1236 (piccolo, or piBRCA2) [111], MAP3K8 [112] regulated by Serine/Arginine-Rich Splicing Factor Kinase [113], QSER1 [39], IQCJ-SCHIP1 [114, 115], ANXA4 [116] and DHDDS [117] among others. The disease-specific proteins and peptides may result from the introduction of new proteins into cir...…”

An Overview of Vasculogenic Mimicry in Breast Cancer

“…The presence of VM in breast cancer has been associated with poor prognosis in several clinical parameters ( Table 1). Overexpression of factors regulating VM in breast tumors, such as HIF1alpha, VE-cadherin, and EPHA2 has also been reported (33)(34)(35)(36). In a mouse breast cancer model, inhibition of angiogenesis promoted VM by expression of VE-Cadherin and other VM regulators in triple-negative tumors (37).…”

Microbiome—Microbial Metabolome—Cancer Cell Interactions in Breast Cancer—Familiar, but Unexplored

“…Later, besides changes to glycolysis and mitochondrial oxidation, other metabolic pathways were shown to be upregulated in breast cancer [25], such as glutamine metabolism [26], lipid and fatty acid [27,28,29,30,31], glutamine-serine pathway [26,32,33], protein translation [34], or cholesterol metabolism [21]. These changes are the consequences of a complex rearrangement of the cellular energy sensor web, such as the activation of hypoxia-inducible factors (HIFs) [35,36], mammalian target of rapamcyin (mTOR) [37,38,39,40], estrogen-related receptors [41], estrogen receptors [19], phosphatidyl-inositol-3 kinase (PI3 kinase) [42,43], AMP-activated protein kinase (AMPK) [44,45], peroxisome proliferator-activated receptor cofactor-1α and β (PGC1α and PGC1β) [46,47], or nuclear respiratory factor 1 (NRF1) [46].…”