Minichromosome maintenance protein 7 as prognostic marker of tumor aggressiveness in pituitary adenoma patients

Coli, Antonella; Sylvia, L.; Fadda, Guido; Scannone, Domenico; Chiloiro, Sabrina; Marinis, Laura De; Lauretti, Liverana; Ranelletti, Franco O.; Lauriola, Libero

doi:10.1530/eje-15-0586

Cited by 28 publications

(25 citation statements)

References 44 publications

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“…High MCM7 protein levels were demonstrated to correlate with prostate cancer progression, poor prognosis of non-small cell lung cancer patients, recurrence of colorectal cancer, as well as distant metastases, high histological grade and poor prognosis is soft tissue sarcomas [58–62]. Examination of MCM7 expression pattern in a series of PAs revealed its significantly higher levels in invasive ACTH-producing adenomas, compared to noninvasive tumors [18]. In the same set of PAs, no significant difference was detected in Ki-67 levels between the invasive and the noninvasive group.…”

Section: Discussionmentioning

confidence: 99%

“…Other biomarkers of PA aggressiveness include fibroblast growth factor receptor 4 (FGFR 4), matrix metalloproteinases (MMPs), presence of growth hormone receptor mutations, loss of chromosome arm 11p and/or 11q and pituitary tumor transforming gene 1 (PTTG1) overexpression [17]. Most recently, Coli et al have reported a significantly increased expression of minichromosome maintenance complex component 7 (MCM7) in invasive ACTH-producing PAs [18] and proposed MCM7 labeling index as a prognostic marker of clinical outcome in PA patients.…”

Section: Introductionmentioning

confidence: 99%

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Increased expression of the microRNA 106b~25 cluster and its host gene MCM7 in corticotroph pituitary adenomas is associated with tumor invasion and Crooke’s cell morphology

et al. 2017

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PurposeMCM7 (minichromosome maintenance complex component 7), a DNA replication licensing factor, is a host gene for the oncogenic miR-106b~25 cluster. It has been recently revealed as a relevant prognostic biomarker in a variety of cancers, including pituitary adenomas. The purpose of this study was to assess whether miR-106b~25 and MCM7 levels correlate with tumor invasiveness in a cohort of ACTH-immunopositive adenomas.MethodsTissue samples were obtained intraoperatively from 25 patients with pituitary adenoma. Tumor invasiveness was assessed according to the Knosp grading scale. MCM7, Ki-67 and TP53 levels were assessed by immunohistochemical staining, while the expression of miR-106b-5p, miR-93-5p, miR-93-3p and miR-25-3p were measured using quantitative real-time PCR performed on RNA isolated from FFPE tissues.ResultsWe have found a significant increase in MCM7 and Ki-67 labeling indices in invasive ACTHomas. Moreover, MCM7 was ubiquitously overexpressed in Crooke’s cell adenomas. The expression of miR-93-5p was significantly elevated in invasive compared to noninvasive tumors. In addition, all four microRNAs from the miR-106b~25 cluster displayed marked upregulation in Crooke’s cell adenomas. Remarkably, MCM7 and miR-106b-5p both strongly correlated with Knosp grade. A combination of MCM7 LI and miR-106b~25 cluster expression was able to accurately differentiate invasive from noninvasive tumors and had a significant discriminatory ability to predict postoperative tumor recurrence/progression.ConclusionsmiR-106b~25 and its host gene MCM7 are potential novel biomarkers for invasive ACTH-immunopositive pituitary adenomas. Additionally, they are both significantly upregulated in rare Crooke’s cell adenomas and might therefore contribute to their aggressive phenotype.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Increased expression of the microRNA 106b~25 cluster and its host gene MCM7 in corticotroph pituitary adenomas is associated with tumor invasion and Crooke’s cell morphology

et al. 2017

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“…Qu K et al found that MCM7 promoted hepatocellular carcinoma progression through cyclin D1-dependent signaling as a prognostic marker for patients [10].Liu YZ et al found that MCM7 may be a potential prognostic marker in non-small cell lung cancer [22]. It has also been reported that MCM7 was a prognostic marker of esophageal cancer [23], endometrial cancer [24] and pituitary adenoma [25]. We have demonstrated that high expression of MCM7 is an independent poor prognostic factor in CRC.…”

Section: Discussionmentioning

confidence: 99%

Up-Regulated Expression of MCM7 is a Poor Prognostic Factor in Colorectal Cancer

Dong¹,

Wang²,

Xu³

et al. 2019

CSROA

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Objective: Colorectal cancer (CRC) is one of the most common malignancies worldwide. MCM7 is one of the important components of DNA replication complex involved in cancer progression. At present, the significance of MCM7 and its mechanisms in CRC development are still unclear. Materials and Methods:Gene expression data of CRC was downloaded from Gene Expression Omnibus (GEO) and TCGA databases. Bioinformatics method was applied to screen CRC differentially expressed genes (DEGs). MCODE and degree value analysis were used to select core genes. The datasets were explored to verify the mRNA expression level of MCM7, and the protein expression level of MCM7 was further verified by Western Blotting and immunohistochemical analysis. Moreover, we also analyzed the correlation between MCM7 and clinical characteristics. The prognostic value of MCM7 in CRC was explored through Kaplan-Meier analysis, univariate and multivariate Cox regression analysis. Results:We confirmed that MCM7 was up-regulated in CRC tissues compared with adjacent non-tumor tissues. MCM7 overexpression was positively associated with lymph node metastasis and TNM stage in CRC. Higher expression of MCM7 showed shorter overall survival rate. Furthermore, MCM7 level could be an independent prognostic factor for CRC. Conclusion:Our study suggested that MCM7 may be a new prognostic factor or molecular target in CRC.The R package 'edgeR' and'limma' were applied to identify the DEGs between CRC tissues and normal tissues. The inclusion standard of DEGs from TCGA was adjusted P <0.01 and log2 Fold Change (FC)>2. DEGs from GEO datasets were selected with the criterion of combined adjusted p< 0.01 and log2FC >1 or log2FC>0.58. Protein-protein interaction (PPI) network construction and module analysisSTRING (https://string-db.org) was applied to construct PPI network for DEGs with confidence score>0.4 and p<0.01. Cytoscape software was used to visualize network. Another, the Molecular Complex Detection (MCODE) app was used to screen modules of PPI network in Cytoscape under degree cutoff =2, node score cutoff=0.2, k-core=2, and max.depth=100. Moreover, the nodes were calculated the degree value.

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“…The host gene of miR‐106b‐25 cluster, MCM7 involves in cell cycle regulation and is a prognostic marker in pituitary adenoma . MCM7 is a proliferation marker in cutaneous T‐cell lymphomas .…”

Section: Discussionmentioning

confidence: 99%

“…12 The host gene of miR-106b-25 cluster, MCM7 involves in cell cycle regulation and is a prognostic marker in pituitary adenoma. 43 MCM7 is a proliferation marker in cutaneous T-cell lymphomas. 44 The current analysis of the RNA sequencing profile of stomach adenocarcinoma reveals the tight co-expression between MCM7 and its intronic counterpart miR-25.…”

Section: Discussionmentioning

confidence: 99%

Amplified 7q21‐22 gene MCM7 and its intronic miR‐25 suppress COL1A2 associated genes to sustain intestinal gastric cancer features

Tamilzhalagan

Rathinam

Ganesan

2017

Molecular Carcinogenesis

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Frequent amplification of 7q21-22 genomic region is known in gastric cancer. Multiple genes including SHFM1, MCM7, and COL1A2 were reported to be the potential cancer candidate genes of this 20 Mb amplicon. This amplicon has two polycistrionic miRNA clusters and in the present study, miR-106b-25 cluster located in intron-13 of MCM7 was identified to express in gastric tumors. Among the 7q21-22 candidate genes, SHFM1 and MCM7 are expressed in intestinal type gastric tumors, whereas COL1A2 is expressed in diffuse type gastric tumors. Across gastric tumors, miR-25 was identified to co-express with MCM7 and SHFM1. On the other hand, negative correlation was observed between miR-25 and COL1A2 expression. miR-25 originating from MCM7 was found capable of selectively targeting the adjacent gene COL1A2. Silencing of miR-25 was found capable of elevating the expression of COL1A2 and inhibiting E-cadherin expression, revealing the diffuse type gastric cancer suppressive role conferred by miR-25. miR-25 was also found to suppress p53, and activate c-Src revealing its intestinal type gastric cancer associated oncogenic functions. Genome-wide expression profiling upon miR-25 silencing reveals that miR-25 is capable of suppressing 40 genes which are co-expressed with COL1A2, involved in epithelial to mesenchymal transition and angiogenesis which are the typical diffuse type gastric cancer features. The results clearly demonstrate 7q21-22 amplification, MCM7, and its intronic miR-25 are the major molecular switches involved in the complex oncogenic circuits of gastric cancer.

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Minichromosome maintenance protein 7 as prognostic marker of tumor aggressiveness in pituitary adenoma patients

Cited by 28 publications

References 44 publications

Increased expression of the microRNA 106b~25 cluster and its host gene MCM7 in corticotroph pituitary adenomas is associated with tumor invasion and Crooke’s cell morphology

Increased expression of the microRNA 106b~25 cluster and its host gene MCM7 in corticotroph pituitary adenomas is associated with tumor invasion and Crooke’s cell morphology

Up-Regulated Expression of MCM7 is a Poor Prognostic Factor in Colorectal Cancer

Amplified 7q21‐22 gene MCM7 and its intronic miR‐25 suppress COL1A2 associated genes to sustain intestinal gastric cancer features

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