Dataset Information

Biomarker signatures of mitochondrial NDUFS3 in invasive breast carcinoma.

ABSTRACT: We present evidence for potential biomarker utility of a mitochondrial complex I subunit, (NDUFS3) in discriminating normal and highly invasive breast carcinoma specimens obtained from clinical patients. Besides being a robust indicator of breast cancer aggressiveness, NDUFS3 also shows clear signatures of a hypoxia/necrosis marker in invasive ductal carcinoma specimens. Statistically significant positive correlation was observed between nuclear grade and NDUFS3 expression level in the tumor specimens analyzed. We support these findings with a plausible mechanism involving mitochondrial complex I assembly defects and/or redox buffering induced mitochondrial dysfunction during the process of cancer cell transformation. From a clinical standpoint, this novel observation adds value in augmenting the current receptor-based biomarkers for better accuracy in diagnosis and predicting survival rate in patients with breast carcinoma.

SUBMITTER: Suhane S

PROVIDER: S-EPMC3171595 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Biomarker signatures of mitochondrial NDUFS3 in invasive breast carcinoma.

Suhane Sonal S Berel Dror D Ramanujan V Krishnan VK

Biochemical and biophysical research communications 20110816 4

We present evidence for potential biomarker utility of a mitochondrial complex I subunit, (NDUFS3) in discriminating normal and highly invasive breast carcinoma specimens obtained from clinical patients. Besides being a robust indicator of breast cancer aggressiveness, NDUFS3 also shows clear signatures of a hypoxia/necrosis marker in invasive ductal carcinoma specimens. Statistically significant positive correlation was observed between nuclear grade and NDUFS3 expression level in the tumor spe ...[more]

PMID: 21867691

Similar Datasets

Project description:BackgroundBone is the most common metastatic site of Breast invasive carcinoma (BRCA). In this study, the bone metastasis-specific regulation network of BRCA was constructed based on prognostic stemness-related signatures (PSRSs), their upstream transcription factors (TFs) and downstream pathways.MethodsClinical information and RNA-seq data of 1,080 primary BRCA samples (1,048 samples without bone metastasis and 32 samples with bone metastasis) were downloaded from The Cancer Genome Atlas (TCGA). The edgeR method was performed to identify differential expressed genes (DEGs). Next, mRNA stemness index (mRNAsi) was calculated by one-class logistic regression (OCLR). To analyze DEGs by classification, similar genes were integrated into the same module by weighted gene co-expression network analysis (WGCNA). Then, univariate and multivariate Cox proportional hazard regression were applied to find the PSRSs. Furthermore, PSRSs, 318 TFs obtained from Cistrome database and 50 hallmark pathways quantified by GSVA were integrated into co-expression analysis. Significant co-expression patterns were used to construct the bone metastasis-specific regulation network. Finally, spatial single-cell RNA-seq and chromatin immunoprecipitation sequence (ChIP-seq) data and multi-omics databases were applied to validate the key scientific hypothesis in the regulation network. Additionally, Connectivity Map (CMap) was utilized to select the potential inhibitors of bone metastasis-specific regulation network in BRCA.ResultsBased on edgeR and WGCNA method, 43 PSRSs were identified. In the bone metastasis-specific regulation network, MAF positively regulated CD248 (R = 0.435, P < 0.001), and hallmark apical junction was the potential pathway of CD248 (R = 0.353, P < 0.001). This regulatory pattern was supported by spatial single-cell RNA sequence, ChIP-seq data and multi-omics online databases. Additionally, alexidine was identified as the possible inhibitor for bone metastasis of BRCA by CMap analysis.ConclusionPSRSs played important roles in bone metastasis of BRCA, and the prognostic model based on PSRSs showed good performance. Especially, we proposed that CD248 was the most significant PSRS, which was positively regulated by MAF, influenced bone metastasis via apical junction pathway. And this axis might be inhibited by alexidine, which providing a potential treatment strategy for bone metastasis of BRCA.

Dataset Information

Biomarker signatures of mitochondrial NDUFS3 in invasive breast carcinoma.

Publications

Biomarker signatures of mitochondrial NDUFS3 in invasive breast carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets