Correction: GATA6 Expression Distinguishes Classical and Basal-like Subtypes in Advanced Pancreatic Cancer

O’Kane, Grainne M.; Grünwald, Barbara; Jang, Gun-Ho; Masoomian, Mehdi; Picardo, Sarah; Grant, Robert C.; Denroche, Robert E.; Zhang, Amy; Wang, Yifan; Miller, Jessica K.; Lam, Bernard; Krzyzanowski, Paul M.; Lungu, Ilinca M.; Bartlett, John M.S.; Peralta, Melanie; Vyas, Foram; Khokha, Rama; Biagi, James; Chadwick, Dianne; Ramotar, Stephanie; Hutchinson, Shawn; Dodd, Anna; Wilson, Julie M.; Notta, Faiyaz; Zogopoulos, George; Gallinger, Steven; Knox, Jennifer J.; Fischer, Sandra E.

doi:10.1158/1078-0432.ccr-22-1272

Cited by 6 publications

(8 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have used IHC to classify PDAC as classical (GATA6 positive; ref. 29) or basal types (positive for KRT5/6, p63, or KRT17; refs. 30,31).…”

Section: Growth Of Pdac Pdos In Basal and Classical Subtypesmentioning

confidence: 99%

Organoid Sensitivity Correlates with Therapeutic Response in Patients with Pancreatic Cancer

Grossman

Muthuswamy

Huang

et al. 2021

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: Pancreatic ductal adenocarcinoma (PDAC) remains a significant health issue. For most patients, there are no options for targeted therapy, and existing treatments are limited by toxicity. The HOPE trial (Harnessing Organoids for PErsonalized Therapy) was a pilot feasibility trial aiming to prospectively generate patient-derived organoids (PDO) from patients with PDAC and test their drug sensitivity and correlation with clinical outcomes. Experimental Design: PDOs were established from a heterogeneous population of patients with PDAC including both basal and classical PDAC subtypes. Results: A method for classifying PDOs as sensitive or resistant to chemotherapy regimens was developed to predict the clinical outcome of patients. Drug sensitivity testing on PDOs correlated with clinical responses to treatment in individual patients. Conclusions: These data support the investigation of PDOs to guide treatment in prospective interventional trials in PDAC.

show abstract

“…Previous studies have used IHC to classify PDAC as classical (GATA6 positive; ref. 29) or basal types (positive for KRT5/6, p63, or KRT17; refs. 30,31).…”

Section: Growth Of Pdac Pdos In Basal and Classical Subtypesmentioning

confidence: 99%

Organoid Sensitivity Correlates with Therapeutic Response in Patients with Pancreatic Cancer

Grossman

Muthuswamy

Huang

et al. 2021

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…We validated the GIP signature associated with elevated NKX6-2 expression using multiple orthogonal approaches, including RNA sequencing performed on archival microdissected IPMN samples and cross-species spatial transcriptomics performed in a genetically engineered model of IPMNs (13,14). Moreover, using a quantitative high-plex platform for protein profiling on archival material (Lunaphore COMET assay), we confirmed that elevated nuclear NKX6-2 was a feature of the gastric subtype of IPMNs, wherein this transcription was co-localized with markers of gastric foveolar mucin (TFF1 and MUC5AC), and with nuclear GATA6, a prototypal marker of socalled "classical" differentiation within pancreatic neoplasms (15). The GIP signature was also recapitulated with overexpression of NKX6-2 in cells derived from a genetically engineered model of IPMNs.…”

Section: Introductionmentioning

confidence: 53%

“…4F, S7D). Expression of transcripts associated with the classical subtype of PDAC, such as GATA6, was also higher in epilesional spots with high NKX6-2 expression (15,30). Moreover, GATA6 and NKX6-2 protein co-localization was observed in the nuclei of LG IPMN using the COMET platform, with overall significantly higher median intensity of GATA6 observed in NKX6-2 positive versus negative nuclei (Fig.…”

Section: Elevated Epithelial Nkx6-2 Expression Is Associated With Gas...mentioning

confidence: 84%

“…On the other hand, enrichment of the classical-like signature was observed in spots with high NKX6-2 expression, with higher levels of GATA6 staining quantified in NKX6-2-expressing nuclei by cyclic IF (15,30). Similarly, SCENIC analysis for aberrant regulons found that even in LG IPMNs, loss of NKX6-2 leads to higher predicted activities of ONECUT-2 and SPDEF regulatory networks, both markers of PDAC progression and aggressive biology (37)(38)(39).…”

Section: Discussionmentioning

confidence: 98%

See 1 more Smart Citation

Spatial Transcriptomics of Intraductal Papillary Mucinous Neoplasms of The Pancreas Identifies NKX6-2 as a Driver of Gastric Differentiation and Indolent Biological Potential

Sans

Makino

Min

et al. 2022

Preprint

View full text Add to dashboard Cite

Intraductal Papillary Mucinous Neoplasms (IPMNs) of the pancreas are bona fide precursor lesions of pancreatic ductal adenocarcinoma (PDAC). The most common subtype of IPMNs harbor a gastric foveolar type lining epithelium, and these low-grade mucinous neoplasms are harbingers of IPMNs with high-grade dysplasia and cancer. The molecular underpinning of gastric differentiation in IPMNs is unknown, although identifying drivers of this indolent phenotype might enable opportunities for intercepting progression to high-grade IPMN and cancer. We conducted spatial transcriptomics on a cohort of patient IPMNs, followed by orthogonal and cross species validation studies, which established the transcription factor NKX6-2 as a key determinant of gastric cell identity in low-grade IPMNs. Loss of NKX6-2 expression is a consistent feature of IPMN progression, while restitution of NKX6-2 in murine IPMN lines recapitulates the aforementioned gastric transcriptional program. Our study identifies NKX6-2 as a previously unknown transcription factor driving indolent gastric differentiation in IPMN pathogenesis.

show abstract

“…Satoshi et al revealed that in urothelial carcinoma, GATA3 is one of the most useful markers in diagnostic surgical pathology and may serve as a reliable prognostic marker in patients with urothelial carcinoma [ 30 ]. Grainne et al found that GATA6 regulates epithelial-mesenchymal transition and tumor dissemination and is a marker of adjuvant chemotherapy response in pancreatic ductal adenocarcinoma (PDAC) [ 31 , 32 ]. Moreover, Andrés et al demonstrated that GATA4 is a potential marker of tumor growth in PDAC and that the expression of GATA4 and GATA6 is a biomarker of poor prognosis and therapeutic response [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Expression profile and prognostic values of GATA family members in kidney renal clear cell carcinoma

Yang

Mei

Nie

et al. 2023

Aging

View full text Add to dashboard Cite

To investigate the possible diagnostic and prognostic biomarkers of kidney renal clear cell carcinoma (KIRC), an integrated study of accumulated data was conducted to obtain more reliable information and more feasible measures. Using the Tumor Immune Estimation Resource (TIMER), University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN), Human Protein Atlas (HPA), Kaplan-Meier plotter database, Gene Expression Profiling Interactive Analysis (GEPIA2) database, cBioPortal, and Metascape, we analyzed the expression profiles and prognoses of six members of the GATA family in patients with KIRC. Compared to normal samples, KIRC samples showed significantly lower GATA2/3/6 mRNA and protein expression levels. KIRC's pathological grades, clinical stages, and lymph node metastases were closely related to GATA2 and GATA5 levels. Patients with KIRC and high GATA2 and GATA5 expression had better overall survival (OS) and recurrence-free survival (RFS), while those with higher expression of GATA3/4/6 had worse outcomes. The role and underlying mechanisms of the GATA family in cell cycle, cell proliferation, metabolic processes, and other aspects were evaluated based on Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses. Furthermore, we found that infiltrating immune cells were highly correlated with GATA expression profiles. These results showed that GATA family members may serve as prognostic biomarkers and therapeutic targets for KIRC.

show abstract

Correction: GATA6 Expression Distinguishes Classical and Basal-like Subtypes in Advanced Pancreatic Cancer

Cited by 6 publications

References 1 publication

Organoid Sensitivity Correlates with Therapeutic Response in Patients with Pancreatic Cancer

Organoid Sensitivity Correlates with Therapeutic Response in Patients with Pancreatic Cancer

Spatial Transcriptomics of Intraductal Papillary Mucinous Neoplasms of The Pancreas Identifies NKX6-2 as a Driver of Gastric Differentiation and Indolent Biological Potential

Expression profile and prognostic values of GATA family members in kidney renal clear cell carcinoma

Contact Info

Product

Resources

About