Expression Pattern of Smad4/GATA3 as a Predictor of Survival in Invasive Ductal Carcinoma of the Breast

Min, Kyueng‐Whan; Kim, Dong-Hoon; Im, Sung Il; Chae, Seoung Wan; Kim, Kyungeun; Sohn, Jin Hee; Lee, Hyun Joo; Do, In‐Gu; Pyo, Jung‐Soo; Kim, Yuil; Kim, Dong Hyun; Yang, Jeongmo; Lee, Sang-Jo; Oh, Young Ha; Oh, Sukjoong; Choi, Sang‐Hoon; Park, Yong Lai; Park, Chan Heun; Kim, Min Jung; Kwon, Mi Jung; Seo, Jinwon

doi:10.1159/000449428

Cited by 10 publications

(6 citation statements)

References 40 publications

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“…In our study, ADRN-specific GATA3 was overexpressed in breast invasive carcinoma (BRCA), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), testicular germ cell tumours (TGCT), STAD, PAAD, and THYM, data that we matched with the mutational profiles of these genes. Consistent with these findings, the predictive value of SMAD4/GATA3 for OS and relapse-free survival (RFS) for breast invasive ductal carcinoma has been reported in previous studies with SMAD4-/GATA3+ patients displaying better OS and RFS [76].…”

Section: Discussionsupporting

confidence: 82%

Deep analysis of neuroblastoma core regulatory circuitries using online databases and integrated bioinformatics shows their pan-cancer roles as prognostic predictors

et al. 2021

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Aim Neuroblastoma is a heterogeneous childhood cancer derived from the neural crest. The dual cell identities of neuroblastoma include Mesenchymal (MES) and Adrenergic (ADRN). These identities are conferred by a small set of tightly-regulated transcription factors (TFs) binding super enhancers, collectively forming core regulatory circuitries (CRCs). The purpose of this study was to gain a deep understanding of the role of MES and ADRN TFs in neuroblastoma and other cancers as potential indicators of disease prognosis, progression, and relapse. Methods To that end, we first investigated the expression and mutational profile of MES and ADRN TFs in neuroblastoma. Moreover, we established their correlation with neuroblastoma risk groups and overall survival while establishing their extended networks with long non-coding RNAs (lncRNAs). Furthermore, we analysed the pan-cancer expression and mutational profile of these TFs and their correlation with patient survival and finally their network connectivity, using a panel of bioinformatic tools including GEPIA2, human pathology atlas, TIMER2, Omicsnet, and Cytoscape. Results We show the association of multiple MES and ADRN TFs with neuroblastoma risk groups and overall survival and find significantly higher expression of various MES and ADRN TFs compared to normal tissues and their association with overall survival and disease-free survival in multiple cancers. Moreover, we report the strong correlation of the expression of these TFs with the infiltration of stromal and immune cells in the tumour microenvironment and with stemness and metastasis-related genes. Furthermore, we reveal extended pan-cancer networks comprising these TFs that influence the tumour microenvironment and metastasis and may be useful indicators of cancer prognosis and patient survival. Conclusion Our meta-analysis shows the significance of MES and ADRN TFs as indicators of patient prognosis and the putative utility of these TFs as potential novel biomarkers.

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Section: Discussionsupporting

confidence: 82%

Deep analysis of neuroblastoma core regulatory circuitries using online databases and integrated bioinformatics shows their pan-cancer roles as prognostic predictors

et al. 2021

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“…Together with two other transcription factors, including oestrogen receptor alpha (ESR1) and Forkhead Box A1 (FOXA1), GATA3/ESR1/FOXA1 forms transcriptional networks responding to the changes of reproductive hormones such as oestrogen and progesterone 30. In the luminal subtypes of human breast carcinoma cells, GATA3 functions through ESR1/FOXA1 transcription network and regulates the expression of target genes, such as Smad4 and fascin, to drive luminal differentiation, which tends to have a better prognosis compare with other non-luminal subtype breast cancer 30 32 33. A similar mechanism was seen in urothelial carcinomas to drive the luminal subtype.…”

Section: Discussionmentioning

confidence: 99%

GATA3 positivity is associated with poor prognosis in patients with oesophageal squamous cell carcinoma

et al. 2022

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AimsGATA-binding protein 3 (GATA3) is a zinc finger transcription factor with diverse biological functions and is an excellent diagnostic marker for breast and urothelial carcinoma. We aimed to study GATA3 expression in oesophageal squamous cell carcinoma (SCC) and its significance with respect to histological features, clinical parameters and overall survival.MethodsWe characterised GATA3 immunohistochemistry in 40 patients with oesophageal SCC. Electronic medical records were reviewed for clinical and follow-up information, as well as patient survival.ResultsEleven (28%) oesophageal SCC were positive for GATA3. The predominant stain patterns were patchy, with either mild or moderate intensities. Patients with GATA3-positive tumours showed significantly shorter overall survival than those with GATA3-negative tumours (p=0.023, Kaplan-Meier survival analysis with log-rank test). In the multivariate Cox proportional hazards regression model, GATA3 positivity was an independent adverse prognostic factor for overall survival (p=0.019, HR 5.671). Surgery, definitive chemotherapy and/or radiotherapy, and initial clinical stage were confirmed as independent prognostic factors.ConclusionTo the best of our knowledge, this is the first study to investigate the incidence of GATA3 positivity in oesophageal SCC and showed GATA3 positivity is associated with poor prognosis in oesophageal SCC.

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“…In a more refined analysis, the miRWalk databases were used to determine validated targets miR-106b-5p genes involved in gastric carcinogenesis and 14 genes from this pathway were found: APC (regulator of the WNT signaling pathway), CCND1 (cyclin D1) CDKN1A (cyclin-dependent kinase inhibitor 1), E2F1, E2F2, E2F3 (transcription factor 1, 2, and 3, respectively), FZD9 (frizzled class receptor 9), MAPK1 (mitogen-activated protein kinase 1), MYC (proto-oncogene BHLH transcription factor), RB1 (transcriptional corepressor 1), SMAD4 (SMAD family member 4), TCF7L2 (transcription factor 7-like 2), TGFBR2 (transforming growth factor β receptor 2), and TP53 (tumor protein p53). Considering the main functions described in the process of carcinogenesis, these genes are involved in cell cycle regulation and tumor progression, cell growth, adhesion and migration, proliferation, differentiation, genome stability, DNA repair, and apoptosis [42][43][44][45][46][47][48][49].…”

Section: Discussionmentioning

confidence: 99%

Analysis of Gene Expression of miRNA-106b-5p and TRAIL in the Apoptosis Pathway in Gastric Cancer

Pereira

Santos

Delabio

et al. 2020

Genes

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Helicobacter pylori (H. pylori) is one of the main causes of gastric gancer. TNF-related apoptosis-inducing ligand (TRAIL) is a protein able to promote apoptosis in cancer cells, however not in gastric cancer, which presents resistance to apoptosis via TRAIL. It is believed that MicroRNA-106b-5p might be involved in this resistance, although its role in Gastric Cancer is unclear. We aimed to determine the expression of microRNA-106b-5p and TRAIL in patients with gastric diseases, infected by H. pylori, and understand the relationship between these genes and their role in apoptosis and the gastric cancer pathways. H. pylori was detected by PCR, gene expression analysis was performed by real-time-qPCR, and bioinformatics analysis was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Cytoscape software. A total of 244 patients were divided into groups (Control, Gastritis, and Cancer); H. pylori was detected in 42.2% of the samples. The cancer group had a poor expression of TRAIL (p < 0.0001) and overexpression of microRNA-106b-5p (p = 0.0005), however, our results confirmed that these genes are not directly related to each other although both are apoptosis-related regulators. Our results also indicated that H. pylori decreases microRNA-106b-5p expression and that this is a carcinogenic bacterium responsible for gastric diseases.

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Expression Pattern of Smad4/GATA3 as a Predictor of Survival in Invasive Ductal Carcinoma of the Breast

Cited by 10 publications

References 40 publications

Deep analysis of neuroblastoma core regulatory circuitries using online databases and integrated bioinformatics shows their pan-cancer roles as prognostic predictors

Deep analysis of neuroblastoma core regulatory circuitries using online databases and integrated bioinformatics shows their pan-cancer roles as prognostic predictors

GATA3 positivity is associated with poor prognosis in patients with oesophageal squamous cell carcinoma

Analysis of Gene Expression of miRNA-106b-5p and TRAIL in the Apoptosis Pathway in Gastric Cancer

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