RNA expression classifiers from a model of breast epithelial cell organization to predict pathological complete response in triple negative breast cancer

Chen, Joan; Russell, Ryan P.; Desai, Trushna; Fiel-Gan, Mary; Bhat, Varun; Gauí, Maria de Fátima Dias; Amendola, Luis Claudio; Vasconcelos, Zilton; Brufsky, Adam; Fournier, Marcia V.; Tannenbaum, Susan

doi:10.1101/2021.02.10.21251517

Cited by 4 publications

(3 citation statements)

References 28 publications

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“…Clinicopathological factors for GSE96058 were downloaded using the R package GEOquary and RNA sequence data annotated with the HUGO symbol were downloaded directly from NCBI Gene Expression Omnibus database [39]. For neoadjuvant chemotherapy response following primary breast cancer cohorts were analyzed: GSE21974 [40], GSE28844 [41], GSE114403 [42], GSE87455 [43,44], GSE25066 [45,46], GSE50948 [47], GSE20271 [48,49], GSE20194 [50,51], GSE180962 [52], GSE22358 [53], GSE22226 [54], GSE163882 [55], GSE34138 [56,57], and GSE16446 [58]. These cohorts were downloaded from the GEO database via the R package GEOquary as well.…”

Section: Patient Data Acquisitionmentioning

confidence: 99%

High RAD51 Gene Expression is Associated with Aggressive Biology and with Poor Survival in Breast Cancer

Patel

Tokumaru

et al. 2021

Preprint

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Purpose: Although DNA repair mechanism is a key to prevent carcinogenesis, its activation in established cancer cells may support their proliferation and aggravate cancer progression. RAD51 cooperates with BRCA2 and is essential in the homologous recombination of DNA repair. To this end, we hypothesized that RAD51 gene expression is associated with cancer cell proliferation and poor prognosis of breast cancer (BC) patients.Methods: A total of 8515 primary BC patients with transcriptome and clinical data from 17 independent cohorts were analyzed. Median was used to divide each cohort into high and low RAD51 expression groups.Results: High RAD51 expression enriched DNA repair gene set and was correlated with DNA repair-related genes. Nottingham histological grade, Ki67 expression and cell proliferation-related gene sets (E2F Targets, G2M Checkpoint and Myc Targets) were all significantly associated with the high RAD51 BC. RAD51 expression was positively correlated with Homologous Recombination Deficiency, as well as both mutation burden and neoantigen that accompanied with higher infiltration of immune cells. Primary BC with lymph node metastases were associated with high expression of RAD51 in 2 cohorts. There was no strong correlation between RAD51 expression and drug sensitivity in cell lines, and RAD51 expression was lower after the neoadjuvant chemotherapy compared to before the treatment. High RAD51 BC was associated with poor prognosis consistently in 3 independent cohorts.Conclusion: RAD51 gene expression is associated with aggressive cancer biology, cancer cell proliferation, and poor survival in breast cancer.

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Section: Patient Data Acquisitionmentioning

confidence: 99%

High RAD51 Gene Expression is Associated with Aggressive Biology and with Poor Survival in Breast Cancer

Patel

Tokumaru

et al. 2021

Preprint

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show abstract

“…Breast cancer RNA-sequencing data and corresponding patients’ clinical characteristics were downloaded from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). We searched for the data from GEO using the keywords “breast cancer”, “triple-negative”, and “drug”, ultimately, obtaining the GSE163882 dataset (n=222) [ 21 ]. This data was downloaded using R GEOquery package (ver.…”

Section: Methodsmentioning

confidence: 99%

Tumor Microenvironment Can Predict Chemotherapy Response of Patients with Triple-Negative Breast Cancer Receiving Neoadjuvant Chemotherapy

Kim¹,

Yu²,

Jung³

et al. 2024

Cancer Res Treat

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Purpose Triple-negative breast cancer (TNBC) is a breast cancer subtype that has poor prognosis and exhibits a unique tumor microenvironment. Analysis of the tumor microbiome has indicated a relationship between the tumor microenvironment and treatment response. Therefore, we attempted to reveal the role of the tumor microbiome in patients with TNBC receiving neoadjuvant chemotherapy.Materials and Methods We collected TNBC patient RNA-sequencing samples from the Gene Expression Omnibus and extracted microbiome count data. Differential and relative abundance were estimated with linear discriminant analysis effect size. We calculated the immune cell fraction with CIBERSORTx and conducted survival analysis using the Cancer Genome Atlas patient data. Correlations between the microbiome and immune cell compositions were analyzed and a prediction model was constructed to estimate drug response.Results Among the pathological complete response group (pCR), the beta diversity varied considerably; consequently, 20 genera and 24 species were observed to express a significant differential and relative abundance. Pandoraea pulmonicola and Brucella melitensis were found to be important features in determining drug response. In correlation analysis, Geosporobacter ferrireducens, Streptococcus sanguinis, and resting natural killer cells were the most correlated factors in the pCR, whereas Nitrosospira briensis, Plantactinospora sp. BC1, and regulatory T cells were key features in the residual disease group.Conclusion Our study demonstrated that the microbiome analysis of tumor tissue can predict chemotherapy response of patients with TNBC. Further, the immunological tumor microenvironment may be impacted by the tumor microbiome, thereby affecting the corresponding survival and treatment response.

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Section: Patient Data Acquisitionmentioning

confidence: 99%

High RAD51 gene expression is associated with aggressive biology and with poor survival in breast cancer

Patel

Tokumaru

et al. 2022

Breast Cancer Res Treat

View full text Add to dashboard Cite

Purpose: Although DNA repair mechanism is a key to prevent carcinogenesis, its activation in established cancer cells may support their proliferation and aggravate cancer progression. RAD51 cooperates with BRCA2 and is essential in the homologous recombination of DNA repair. To this end, we hypothesized that RAD51 gene expression is associated with cancer cell proliferation and poor prognosis of breast cancer (BC) patients.Methods: A total of 8515 primary BC patients with transcriptome and clinical data from 17 independent cohorts were analyzed. Median was used to divide each cohort into high and low RAD51 expression groups.Results: High RAD51 expression enriched DNA repair gene set and was correlated with DNA repair-related genes. Nottingham histological grade, Ki67 expression and cell proliferation-related gene sets (E2F Targets, G2M Checkpoint and Myc Targets) were all signi cantly associated with the high RAD51 BC.RAD51 expression was positively correlated with Homologous Recombination De ciency, as well as both mutation burden and neoantigen that accompanied with higher in ltration of immune cells. Primary BC with lymph node metastases were associated with high expression of RAD51 in 2 cohorts. There was no strong correlation between RAD51 expression and drug sensitivity in cell lines, and RAD51 expression was lower after the neoadjuvant chemotherapy compared to before the treatment. High RAD51 BC was associated with poor prognosis consistently in 3 independent cohorts. Conclusion: RAD51 gene expression is associated with aggressive cancer biology, cancer cell proliferation, and poor survival in breast cancer.

show abstract

RNA expression classifiers from a model of breast epithelial cell organization to predict pathological complete response in triple negative breast cancer

Cited by 4 publications

References 28 publications

High RAD51 Gene Expression is Associated with Aggressive Biology and with Poor Survival in Breast Cancer

High RAD51 Gene Expression is Associated with Aggressive Biology and with Poor Survival in Breast Cancer

Tumor Microenvironment Can Predict Chemotherapy Response of Patients with Triple-Negative Breast Cancer Receiving Neoadjuvant Chemotherapy

High RAD51 gene expression is associated with aggressive biology and with poor survival in breast cancer

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