MCM2-7 in Clear Cell Renal Cell Carcinoma: MCM7 Promotes Tumor Cell Proliferation

Zhang, Junneng; Zhang, Huanzong; Wang, Yinghui; Wang, Qingshui

doi:10.3389/fonc.2021.782755

Cited by 14 publications

(12 citation statements)

References 54 publications

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“…7 H). As a potential marker of cell proliferation, MCM2-7 is required for DNA replication, and is related to the progression and prognosis in liver cancer 18 , 19 .PLK1 is an important cell cycle-regulated protein $kinase that is positively correlated with HAUS5 mRNA expression. As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Comprehensive analysis of the correlation of the pan-cancer gene HAUS5 with prognosis and immune infiltration in liver cancer

Zhang

Yang

et al. 2023

Sci Rep

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Liver hepatocellular carcinoma (LIHC) is one of the most common malignancies and places a heavy burden on patients worldwide. HAUS augmin-like complex subunit 5 (HAUS5) is involved in the occurrence and development of various cancers. However, the functional role and significance of HAUS5 in LIHC remain unclear. The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Cancer Cell Line Encyclopedia (CCLE) and Gene Expression Omnibus (GEO) databases were used to analyze the mRNA expression of HAUS5. The value of HAUS5 in predicting LIHC prognosis and the relationship between HAUS5 and clinicopathological features were assessed by the Kaplan–Meier plotter and UALCAN databases. Functional enrichment analyses and nomogram prediction model construction were performed with the R packages. The LinkedOmics database was searched to reveal co-expressed genes associated with HAUS5. The relationship between HAUS5 expression and immune infiltration was explored by searching the TISIDB database and single-sample gene set enrichment analysis (ssGSEA). The Clinical Proteomic Tumor Analysis Consortium (CPTAC) and the Human Protein Atlas (HPA) databases were used to evaluate HAUS5 protein expression. Finally, the effect of HAUS5 on the proliferation of hepatoma cells was verified by CCK-8, colony formation and EdU assays. HAUS5 is aberrantly expressed and associated with a poor prognosis in most tumors, including LIHC. The expression of HAUS5 is significantly correlated with clinicopathological indicators in patients with LIHC. Functional enrichment analysis showed that HAUS5 was closely related to DNA replication, cell cycle and p53 signaling pathway. HAUS5 may serve as an independent risk factor for LIHC prognosis. The nomogram based on HAUS5 had area under the curve (AUC) values of 0.74 and 0.77 for predicting the 3-year and 5-year overall survival (OS) of LIHC patients. Immune correlation analysis showed that HAUS5 was significantly associated with immune infiltration. Finally, the results of in vitro experiments showed that when HAUS5 was knocked down, the proliferation of hepatoma cells was significantly decreased. The pan-oncogene HAUS5 is a positive regulator of LIHC progression and is closely associated with a poor prognosis in LIHC. Moreover, HAUS5 is involved in immune infiltration in LIHC. HAUS5 may be a new prognostic marker and therapeutic target for LIHC patients.

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Section: Resultsmentioning

confidence: 99%

Comprehensive analysis of the correlation of the pan-cancer gene HAUS5 with prognosis and immune infiltration in liver cancer

Zhang

Yang

et al. 2023

Sci Rep

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“…We first screened the clinicopathological parameters associated with the therapeutic effects of second-line treatment with axitinib using univariate Cox proportional-hazards regression (CPHR) analysis. Because CPHR is not used to analyze multidimensional survival datasets, the least absolute shrinkage and selection operator (LASSO) technique was subsequently performed for variable selection and shrinkage from many clinical variables identified by univariate CPHR, using the glmnet package of R ( 8 , 14 ). Finally, we identified and then established a predictive model based on four clinical parameters (albumin, calcium, IMDC grade, and adverse reaction grade) through multivariate CPHR.…”

Section: Methodsmentioning

confidence: 99%

Development and validation of a nomogram to evaluate the therapeutic effects of second-line axitinib in patients with metastatic renal cell carcinoma

Lin

Peng²,

Zhang³

et al. 2023

Front. Oncol.

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The unpredictable biological behavior and tumor heterogeneity of metastatic renal cell carcinoma (mRCC) cause significant differences in axitinib efficacy. The aim of this study is to establish a predictive model based on clinicopathological features to screen patients with mRCC who can benefit from axitinib treatment. A total of 44 patients with mRCC were enrolled and divided into the training set and validation set. In the training set, variables related with the therapeutic efficacy of second-line treatment with axitinib were screened through univariate Cox proportional hazards regression and least absolute shrinkage and selection operator analyses. A predictive model was subsequently established to assess the therapeutic efficacy of second-line treatment with axitinib. The predictive performance of the model was evaluated by analyzing the concordance index and time-dependent receiver operating characteristic, calibration, and decision curves. The accuracy of the model was similarly verified in the validation set. The International Metastatic RCC Database Consortium (IMDC) grade, albumin, calcium, and adverse reaction grade were identified as the best predictors of the efficacy of second-line axitinib treatment. Adverse reaction grade was an independent prognostic index that correlated with the therapeutic effects of second-line treatment with axitinib. Concordance index value of the model was 0.84. Area under curve values for the prediction of 3-, 6-, and 12-month progression-free survival after axitinib treatment were 0.975, 0.909, and 0.911, respectively. The calibration curve showed a good fit between the predicted and actual probabilities of progression-free survival at 3, 6, and 12 months. The results were verified in the validation set. Decision curve analysis revealed that the nomogram based on a combination of four clinical parameters (IMDC grade, albumin, calcium, and adverse reaction grade) had more net benefit than adverse reaction grade alone. Our predictive model can be useful for clinicians to identify patients with mRCC who can benefit from second-line treatment with axitinib.

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“…115,225,[273][274][275] Consistent with this notion, overexpression of MCM5 also associates with tumor stages, which appears to be potential diagnostic and prognostic markers in thyroid cancer, 276,277 ovarian cancer, 269,[278][279][280] bladder cancer, [281][282][283] and renal cell carcinoma. 284 On the contrary, WGCNA combining with TCGA and GEO analysis identified that exceptional expression of MCM6 reflects pathologic stage of multiple tumors, serving as putative biomarkers for breast cancer, [285][286][287] gastric cancer, 288,289 renal cell carcinoma, 215,290,291 HCC, [292][293][294][295] and non-small cell lung carcinoma. 217,296,297 Meanwhile, MCM7 is widely regarded as an extensive biomarker in multiple tumor types since its overexpression pattern.…”

Section: Mcms As Diagnostic and Prognostic Biomarkersmentioning

confidence: 99%

“…On the contrary, WGCNA combining with TCGA and GEO analysis identified that exceptional expression of MCM6 reflects pathologic stage of multiple tumors, serving as putative biomarkers for breast cancer, 285–287 gastric cancer, 288,289 renal cell carcinoma, 215,290,291 HCC, 292–295 and non‐small cell lung carcinoma 217,296,297 . Meanwhile, MCM7 is widely regarded as an extensive biomarker in multiple tumor types since its overexpression pattern 233,234,298–310 .…”

Section: Dna Replication Disease and Therapymentioning

confidence: 99%

DNA replication: Mechanisms and therapeutic interventions for diseases

Song

Shen

Mahasin

et al. 2023

MedComm

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Accurate and integral cellular DNA replication is modulated by multiple replication-associated proteins, which is fundamental to preserve genome stability. Furthermore, replication proteins cooperate with multiple DNA damage factors to deal with replication stress through mechanisms beyond their role in replication. Cancer cells with chronic replication stress exhibit aberrant DNA replication and DNA damage response, providing an exploitable therapeutic target in tumors. Numerous evidence has indicated that posttranslational modifications (PTMs) of replication proteins present distinct functions in DNA replication and respond to replication stress. In addition, abundant replication proteins are involved in tumorigenesis and development, which act as diagnostic and prognostic biomarkers in some tumors, implying these proteins act as therapeutic targets in clinical. Replication-target cancer therapy emerges as the times require. In this context, we outline the current investigation of the DNA replication mechanism, and simultaneously enumerate the aberrant expression of replication proteins as hallmark for various diseases, revealing their therapeutic potential for target therapy. Meanwhile, we also discuss current observations that the novel PTM of replication proteins in response to replication stress, which seems to be a promising strategy to eliminate diseases.

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MCM2-7 in Clear Cell Renal Cell Carcinoma: MCM7 Promotes Tumor Cell Proliferation

Cited by 14 publications

References 54 publications

Comprehensive analysis of the correlation of the pan-cancer gene HAUS5 with prognosis and immune infiltration in liver cancer

Comprehensive analysis of the correlation of the pan-cancer gene HAUS5 with prognosis and immune infiltration in liver cancer

Development and validation of a nomogram to evaluate the therapeutic effects of second-line axitinib in patients with metastatic renal cell carcinoma

DNA replication: Mechanisms and therapeutic interventions for diseases

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