Postpartum breast cancer has a distinct molecular profile that predicts poor outcomes.
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ABSTRACT:
SUBMITTER: Jindal S
PROVIDER: S-EPMC8566602 | biostudies-literature | 2021 Nov
REPOSITORIES: biostudies-literature
Publications
Postpartum breast cancer has a distinct molecular profile that predicts poor outcomes.
Jindal Sonali S Pennock Nathan D ND Sun Duanchen D Horton Wesley W Ozaki Michelle K MK Narasimhan Jayasri J Bartlett Alexandra Q AQ Weinmann Sheila S Goss Paul E PE Borges Virginia F VF Xia Zheng Z Schedin Pepper P
Nature communications 20211103 1
Young women's breast cancer (YWBC) has poor prognosis and known interactions with parity. Women diagnosed within 5-10 years of childbirth, defined as postpartum breast cancer (PPBC), have poorer prognosis compared to age, stage, and biologic subtype-matched nulliparous patients. Genomic differences that explain this poor prognosis remain unknown. In this study, using RNA expression data from clinically matched estrogen receptor positive (ER+) cases (n = 16), we observe that ER+ YWBC can be diffe ...[more]
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Project description:PurposePatients with postpartum breast cancer diagnosed after cessation of breastfeeding (postweaning, PP-BCPW) have a particularly poor prognosis compared with patients diagnosed during lactation (PP-BCDL), or to pregnant (Pr-BC) and nulliparous (NP-BC) patients, regardless of standard prognostic characteristics. Animal studies point to a role of the involution process in stimulation of tumor growth in the mammary gland. However, in women, the molecular mechanisms that underlie this poor prognosis of patients with PP-BCPW remain vastly underexplored, due to of lack of adequate patient numbers and outcome data.Experimental designWe explored whether distinct prognostic features, common to all breast cancer molecular subtypes, exist in postpartum tumor tissue. Using detailed breastfeeding data, we delineated the postweaning period in PP-BC as a surrogate for mammary gland involution and performed whole transcriptome sequencing, immunohistochemical, and (multiplex) immunofluorescent analyses on tumor tissue of patients with PP-BCPW, PP-BCDL, Pr-BC, and NP-BC.ResultsWe found that patients with PP-BCPW having a low expression level of an immunoglobulin gene signature, but high infiltration of plasma B cells, have an increased risk for metastasis and death. Although PP-BCPW tumor tissue was also characterized by an increase in CD8+ cytotoxic T cells and reduced distance among these cell types, these parameters were not associated with differential clinical outcomes among groups.ConclusionsThese data point to the importance of plasma B cells in the postweaning mammary tumor microenvironment regarding the poor prognosis of PP-BCPW patients. Future prospective and in-depth research needs to further explore the role of B-cell immunobiology in this specific group of young patients with breast cancer.
| S-EPMC10502474 | biostudies-literature
Project description:ObjectiveMenage a trois 1 (MAT1) is a targeting subunit of cyclin-dependent kinase-activating kinase and general transcription factor IIH kinase, which modulates cell cycle, transcription and DNA repair. Its dysregulation is responsible for diseases including cancers. To further explore the role of MAT1 in breast cancer, we investigated the pathways in which MAT1 might be involved, the association between MAT1 and molecular subtypes, and the role of MAT1 in clinical outcomes of breast cancer patients.MethodsWe conducted immunohistochemistry staining on tissue microarray and immunofluorescence staining on sections of MAT1 stable breast cancer cells. Also, we performed Kyoto Encyclopedia of Genes and Genomes pathway analysis, correlation analysis and prognosis analysis on public databases.ResultsMAT1 was involved in multiple pathways including normal physiology signaling and disease-related signaling. Furthermore, MAT1 positively correlated with the protein status of estrogen receptor and progesterone receptor, and was enriched in luminal-type and human epidermal growth factor receptor 2-enriched breast cancer in comparison with basal-like subtype at both mRNA and protein levels. Correlation analysis revealed significant association between MAT1 mRNA amount and epithelial markers, mesenchymal markers, cancer stem cell markers, apoptosis markers, transcription markers and oncogenes. Consistently, the results of immunofluorescence stain indicated that MAT1 overexpression enhanced the protein abundance of epidermal growth factor receptor, vimentin, sex determining region Y-box 2 and sine oculis homeobox homolog 1. Importantly, Kaplan-Meier Plotter analysis reflected that MAT1 could serve as a prognostic biomarker predicting worse relapse-free survival and metastasis-free survival.ConclusionsMAT1 is correlated with molecular subtypes and is associated with unfavorable prognosis for breast cancer patients.
| S-EPMC6037588 | biostudies-literature
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| S-EPMC2584947 | biostudies-other
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| S-EPMC10688681 | biostudies-literature
Project description:BACKGROUND:DNA methylation (DNAm) age was found to be an indicator for all-cause mortality, cancer incidence, and longevity, but no study has involved in the associations of DNAm age with the prognosis of breast cancer. METHODS:We retrieved information of 1076 breast cancer patients from Genomic Data Commons (GDC) data portal on March 30, 2017, including breast cancer DNAm profiling, demographic features, clinicopathological parameters, recurrence, and all-cause fatality. Horvath's method was applied to calculate the DNAm age. Cox proportional hazards regression models were used to test the associations between DNAm age of the cancerous tissues and the prognosis (recurrence of breast cancer and all-cause fatality) with or without adjusting for chronological age and clinicopathological parameters. RESULTS:The DNAm age was markedly decelerated in the patients who were premenopausal, ER or PR negative, HER2-enriched or basal-like than their counterparts. In the first five-year follow-up dataset for survival, every ten-year increase in DNAm age was associated with a 15% decrease in fatality; subjects with DNAm age in the second (HR: 0.52; 95%CI: 0.29-0.92), the third (HR: 0.49; 95%CI: 0.27-0.87) and the fourth quartile (HR: 0.38; 95%CI: 0.20-0.72) had significant longer survival time than those in the first quartile. In the first five-year follow-up dataset for recurrence, every ten-year increase in DNAm age was associated with a 14% decrease of the recurrence; in the categorical analysis, a clear dose-response was shown (P for trend =0.02) and the fourth quartile was associated with a longer recurrence free survival (HR: 0.32; 95%CI: 0.14-0.74). In the full follow-up dataset, similar results were obtained. CONCLUSIONS:DNAm age of breast cancer tissue, which associated with menopausal status and pathological features, was a strong independent predictor of the prognosis. It was suggested that the prognosis of breast cancer was related to intrinsic biological changes and specific molecular targets for treatment of breast cancer may be implicit.
| S-EPMC6191915 | biostudies-literature
Project description:BackgroundAccumulating studies have focused on the oncogenic roles of the newly identified lncRNAs in human cancers. The aim of this study was to examine the expression pattern of Linc00959 in BC and to evaluate its biological role and clinical significance in prediction of prognosis.MethodsExpression of Linc00959 was detected in 290 BC tissues by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). We analyzed the relationship between Linc00959 expression and clinic pathological features of BC patients. The correlation was calculated by SPSS software.ResultsOur results revealed that Linc00959 expression was correlated with ER status (p = 0.005), PR status (p = 0.036), Ki67 (p = 0.025) and HER2 status (p = 0.009). The Kaplan-Meier survival curves indicated that the overall survival (OS) (p = 0.022) and relapse-free survival (RFS) (p = 0.002) were significantly poor in high Linc00959 expression BC patients (p = 0.023). Furthermore, the survival analysis by Cox regression showed that Linc00959 served as an independent prognostic marker in breast cancer (p = 0.004).ConclusionOur studies indicate that Linc00959 is significantly associated with poor prognosis and may represent a new marker of prognosis in breast cancer.
| S-EPMC6381736 | biostudies-literature