Differential Diagnosis of Reactive Mesothelial Cells and Malignant Mesothelioma Cells Using the Cell Proliferation Markers Minichromosome Maintenance Protein 7, Geminin, Topoisomerase II Alpha and Ki-67

Kimura, Futoshi; Okayasu, Isao; Kakinuma, Hirokuni; Satoh, Yukitoshi; Kuwao, Sadahito; Saegusa, Makoto; Watanabe, Jun

doi:10.1159/000350262

Cited by 16 publications

(15 citation statements)

References 24 publications

(38 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Suggesting that geminin is a genuine oncogene that promotes genomic instability when overexpressed as a wild-type protein. In keeping with that, geminin is overexpressed in many tumor types [12]–[16], and to our knowledge the protein is wild type in these tumors. In fact, we recently analyzed a cohort of 150 DNA samples freshly isolated from patients’ breast tumors and found that geminin gene carries no mutation or any alterations that can affect the protein in all these tumors (ElShamy WM and Iglehart D, unpublished data).…”

Section: Introductionsupporting

confidence: 66%

Geminin Overexpression Promotes Imatinib Sensitive Breast Cancer: A Novel Treatment Approach for Aggressive Breast Cancers, Including a Subset of Triple Negative

et al. 2014

View full text Add to dashboard Cite

Breast cancer is the second leading cause of cancer-related deaths in women. Triple negative breast cancer (TNBC) is an aggressive subtype that affects 10–25% mostly African American women. TNBC has the poorest prognosis of all subtypes with rapid progression leading to mortality in younger patients. So far, there is no targeted treatment for TNBC. To that end, here we show that c-Abl is one of several tyrosine kinases that phosphorylate and activate geminin’s ability to promote TNBC. Analysis of >800 breast tumor samples showed that geminin is overexpressed in ∼50% of all tumors. Although c-Abl is overexpressed in ∼90% of all tumors, it is only nuclear in geminin overexpressing tumors. In geminin-negative tumors, c-Abl is only cytoplasmic. Inhibiting c-Abl expression or activity (using imatinib or nilotinib) prevented geminin Y150 phosphorylation, inactivated the protein, and most importantly converted overexpressed geminin from an oncogene to an apoptosis inducer. In pre-clinical orthotopic breast tumor models, geminin-overexpressing cells developed aneuploid and invasive tumors, which were suppressed when c-Abl expression was blocked. Moreover, established geminin overexpressing orthotopic tumors regressed when treated with imatinib or nilotinib. Our studies support imatinib/nilotonib as a novel treatment option for patients with aggressive breast cancer (including a subset of TNBCs)-overexpressing geminin and nuclear c-Abl.

show abstract

Section: Introductionsupporting

confidence: 66%

Geminin Overexpression Promotes Imatinib Sensitive Breast Cancer: A Novel Treatment Approach for Aggressive Breast Cancers, Including a Subset of Triple Negative

et al. 2014

View full text Add to dashboard Cite

show abstract

“… 55 Similar studies of MCM7 also have been reported in gastric cancer (GC), 56 esophageal lesions, 57 reactive mesothelial cells, and malignant cells. 58 , 59 Because of the close relationship between MCM gene and cell proliferation, MCM genes are also found to be associated with tumor progression. Overexpression of MCM7 was significantly associated with prostate cancer progression, relapse, local invasion, and a worse tumor grade, 60 as well as in OSCC development and metastasis.…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of minichromosome maintenance mRNA expression in early-stage pancreatic ductal adenocarcinoma patients after pancreaticoduodenectomy

Liao¹,

Han²,

Wang³

et al. 2018

CMAR

View full text Add to dashboard Cite

BackgroundThe aim of the current study was to investigate the potential prognostic value of minichromosome maintenance (MCM) genes in patients with early-stage pancreatic ductal adenocarcinoma (PDAC) after pancreaticoduodenectomy by using the RNA-sequencing dataset from The Cancer Genome Atlas (TCGA).MethodsAn RNA-sequencing dataset of 112 early-stage PDAC patients who received a pancreaticoduodenectomy was obtained from TCGA. Survival analysis was used to identify potential prognostic values of MCM genes in PDAC overall survival (OS).ResultsThrough mining public databases, we observed that MCM genes (MCM2, MCM3, MCM4, MCM5, MCM6, and MCM7) were upregulated in pancreatic cancer tumor tissue and have a strong positive coexpression with each other. Multivariate survival analysis indicated that a high expression of MCM4 significantly increased the risk of death in patients with PDAC, and time-dependent receiver operating characteristic analysis showed an area under the curve of 0.655, 0.587, and 0.509 for a 1-, 2-, and 3-year PDAC OS prediction, respectively. Comprehensive survival analysis of MCM4 using stratified and joint effects survival analysis suggests that MCM4 may be an independent prognostic indicator for PDAC OS. Gene set enrichment analysis indicated that MCM4 may participate in multiple biologic processes and pathways, including DNA replication, cell cycle, tumor protein p53, and Notch signaling pathways, thereby affecting prognosis of PDAC patients.ConclusionsOur study indicates that MCM2–7 were upregulated in pancreatic cancer tumor tissues, and mRNA expression of MCM4 may serve as an independent prognostic indicator for PDAC OS prediction after pancreaticoduodenectomy.

show abstract

“…In the same study by Kimura, other proliferative markers were examined on PEs: minichromosome maintenance protein 7 (MCM7), geminin, and topoisomerase II alpha (Topo II α). All of these proteins showed high expression in MPM; their sensitivity and specificity were 100% and 100% for MCM7 (cut-off value 20.0%), 88% and 70% for geminin (cutoff value 4.5%), 88% and 92% for Topo II α (cut-off value 11.0%), respectively (22).…”

Section: Diagnostic Markers By Ihc or Fishmentioning

confidence: 98%

“…Ki-67 was additionally analyzed by Hasteh et al, who found no significant difference between reactive MH and MPM cases (10), as well as by Kimura et al on PEs, showing a sensitivity of 78% and a specificity of 79% (22). In the same study by Kimura, other proliferative markers were examined on PEs: minichromosome maintenance protein 7 (MCM7), geminin, and topoisomerase II alpha (Topo II α).…”

Section: Diagnostic Markers By Ihc or Fishmentioning

confidence: 99%

Molecular markers and new diagnostic methods to differentiate malignant from benign mesothelial pleural proliferations: a literature review

Bruno¹,

Alì²,

Fontanini³

2018

J. Thorac. Dis.

View full text Add to dashboard Cite

Malignant pleural mesothelioma (MPM) is an aggressive tumor associated with asbestos exposure. Histopathological analysis of pleural tissues is the gold standard for diagnosis; however, it can be difficult to differentiate malignant from benign pleural lesions. The purpose of this review is to describe the most important biomarkers and new diagnostic tools suggested for this differential diagnosis. There are many studies concerning the separation between MPM and benign pleural proliferations from both pleural tissues or effusions; most of them are based on the evaluation of one or few biomarkers by immunohistochemistry (IHC) or enzyme-linked immunosorbent assays (ELISAs), whereas others focused on the identification of MPM signatures given by microRNA (miRNA) or gene expression profiles as well as on the combination of molecular data and classification algorithms. None of the reported biomarkers showed adequate diagnostic accuracy, except for p16 [evaluated by fluorescent in situ hybridization (FISH)] and BAP1 (evaluated by IHC), both biomarkers are recommended by the International Mesothelioma Interest Group guidelines for histological and cytological diagnosis. BAP1 and p16 showed a specificity of 100% in discerning malignant from benign lesions because they are exclusively unexpressed or deleted in MPM. However, their sensitivity, even when used together, is not completely sufficient, and absence of their alterations cannot confirm the benign nature of the lesion. Recently, the availability of new techniques and increasing knowledge regarding MPM genetics led to the definition of some molecular panels, including genes or miRNAs specifically deregulated in MPM, that are extremely valuable for differential diagnosis. Moreover, the development of classification algorithms is facilitating the application of molecular data for clinical practice. Data regarding new diagnostic tools and MPM signatures are absolutely promising; however, before their application in clinical practice, a prospective validation is necessary, as these approaches could surely improve the differential diagnosis between malignant and benign pleural lesions.

show abstract

Differential Diagnosis of Reactive Mesothelial Cells and Malignant Mesothelioma Cells Using the Cell Proliferation Markers Minichromosome Maintenance Protein 7, Geminin, Topoisomerase II Alpha and Ki-67

Cited by 16 publications

References 24 publications

Geminin Overexpression Promotes Imatinib Sensitive Breast Cancer: A Novel Treatment Approach for Aggressive Breast Cancers, Including a Subset of Triple Negative

Geminin Overexpression Promotes Imatinib Sensitive Breast Cancer: A Novel Treatment Approach for Aggressive Breast Cancers, Including a Subset of Triple Negative

Prognostic value of minichromosome maintenance mRNA expression in early-stage pancreatic ductal adenocarcinoma patients after pancreaticoduodenectomy

Molecular markers and new diagnostic methods to differentiate malignant from benign mesothelial pleural proliferations: a literature review

Contact Info

Product

Resources

About