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Transcriptional expressions of Chromobox 1/2/3/6/8 as independent indicators for survivals in hepatocellular carcinoma patients.

ABSTRACT: Chromobox (CBX) proteins are important components of epigenetic regulation complexes known to play key roles in hepatocellular carcinoma (HCC). Little is known about the function of distinct CBXs in HCC. To address this issue, the study investigated the roles of CBXs in the prognosis of HCC using ONCOMINE, UALCAN, Human Protein Atlas, Kaplan-Meier Plotter, c-BioPortal databases. Over expressions of 8 CBXs members were found to be significantly associated with clinical cancer stages and pathological tumor grades in HCC patients. Besides, higher mRNA expressions of CBX1/2/3/6/8 were found to be significantly associated with shorter overall survival (OS) in HCC patients, while higher mRNA expression of CBX7 was associated with favorable OS. Multivariate analysis also showed that high mRNA expressions of CBX1/2/3/6/8 were independent prognostic factors for shorter OS of HCC patients. Moreover, high mutation rate of CBXs (51%) was also observed in HCC patients, and genetic alteration in CBXs was associated with shorter OS and disease-free survival (DFS) in HCC patients. Taken together, these results indicated that CBX1/2/3/6/8 could be prognostic biomarkers for survivals of HCC patients.

SUBMITTER: Ning G

PROVIDER: S-EPMC6286817 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Transcriptional expressions of Chromobox 1/2/3/6/8 as independent indicators for survivals in hepatocellular carcinoma patients.

Ning Gang G Huang Yan-Lin YL Zhen Li-Min LM Xu Wen-Xiong WX Jiao Qian Q Yang Fang-Ji FJ Wu Li-Na LN Zheng Yong-Yuan YY Song Jie J Wang Yen-Sheng YS Xie Chan C Peng Liang L

Aging 20181101 11

Chromobox (CBX) proteins are important components of epigenetic regulation complexes known to play key roles in hepatocellular carcinoma (HCC). Little is known about the function of distinct CBXs in HCC. To address this issue, the study investigated the roles of CBXs in the prognosis of HCC using ONCOMINE, UALCAN, Human Protein Atlas, Kaplan-Meier Plotter, <i>c-BioPortal</i> databases. Over expressions of 8 CBXs members were found to be significantly associated with clinical cancer stages and pa ...[more]

PMID: 30481161

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Project description:The study was conducted to unveil the significance of protein phosphatases in the prognosis of hepatocellular carcinoma (HCC) patients and its related molecular biological attributes as well as to discover novel potential biomarkers for therapeutic significance and diagnostic purposes that may benefit clinical practice. Analyzing a data set from 159 HCC patients using high-throughput phosphoproteomics, we examined the dysregulated expression of protein phosphatases. Employing bioinformatic and pathway analyses, we explored differentially expressed genes linked to protein phosphatases. A protein-protein interaction network was constructed using the search tool for the retrieval of interacting genes/proteins database. We quantified a total of 11,547 phosphorylation sites associated with 4043 phosphoproteins from HCC patients. Within this data set, we identified 105 identified phosphorylation sites associated with protein phosphatases; 28 genes were upregulated and 3 were downregulated in HCC. Enriched pathways using Gene Set Enrichment Analysis encompassed oocyte meiosis, proteoglycans in cancer, the oxytocin signaling pathway, the cGMP-PKG signaling pathway, the vascular smooth muscle, and the cAMP signaling pathway. The Kyoto encyclopedia of genes and genomes (KEGG) analysis highlighted pathways like mitogen-activated protein kinase, AMPK, and PI3K-Akt, indicating potential involvement in HCC progression. Notably, the PPI network identified hub genes, emphasizing their interconnections and potential roles in HCC. In our study, we found significantly upregulated levels of CDC25C, PPP1R13L, and PPP1CA, which emerge as promising avenues. This significant expression could serve as potent diagnostic and prognostic markers to enhance the effectiveness of HCC cancer treatment, offering efficiency and accuracy in patient assessment. The findings regarding protein phosphatases reveal their elevated expression in HCC, correlating with unfavorable prognosis. Moreover, the outcomes of gene ontology and KEGG pathway analyses suggest that protein phosphatases may influence liver cancer by engaging diverse targets and pathways, ultimately fostering the progression of HCC. These results underscore the substantial potential of protein phosphatases as key contributors to HCC's development and advancement. This insight holds promise for identifying therapeutic targets and charting research avenues to enhance the comprehension of the intricate molecular mechanisms underpinning HCC.

Project description:BackgroundThe chromobox family, a critical component of epigenetic regulators, participates in the tumorigenesis and progression of many malignancies. However, the roles of the CBX family members (CBXs) in glioblastoma (GBM) remain unclear.MethodsThe mRNA expression of CBXs was analyzed in tissues and cell lines by Oncomine and Cancer Cell Line Encyclopedia (CCLE). The differential expression of CBXs at the mRNA level was explored in The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases with the "beeswarm" R package. The protein expression of CBXs in GBM was further examined on Human Protein Atlas (HPA). The correlations between CBXs and IDH mutation and between CBXs and GBM subtypes were investigated in the TCGA portal and CGGA database with the "survminer" R package. The alteration of CBXs and their prognostic value were further determined via the cBioPortal and CGGA database with the "survival" R package. The univariate and multivariate analyses were performed to screen out the independent prognostic roles of CBXs in the CGGA database. Cytoscape was used to visualize the functions and related pathways of CBXs in GBM. U251 and U87 glioma cells with gene intervention were used to validate the role of CBX7/8 in tumor proliferation and invasion. Proliferation/invasion-related markers were conducted by Western blot and immunostaining.ResultsCBXs presented significantly differential expressions in pan-cancers. CBX2/3/5/8 were upregulated, whereas CBX6/7 were downregulated at mRNA level in GBM of TCGA and CGGA databases. Similarly, high expression of CBX2/3/5 and low expression of CBX6/8 were further confirmed at the protein level in the HPA. CBX2/6/7 were positively correlated with IDH mutation and CBX1/2/4/5/8 were closely related to GBM subtypes. CBX7 and CBX8 presented the independent prognostic factors for GBM patient survival. GO and KEGG analyses indicated that CBXs were closely related to the histone H3-K36, PcG protein complex, ATPase, and Wnt pathway. The overexpression of CBX7 and underexpression of CBX8 significantly inhibited the proliferation and invasion of glioma cells in vivo and in vitro.ConclusionOur results suggested that CBX7 and CBX8 served as independent prognostic indicators that promoted the proliferation and invasion of glioma cells, providing a promising strategy for diagnosing and treating GBM.

Project description:BackgroundHepatocellular carcinoma (HCC) is the most common and deadly type of liver cancer. Autophagy is the process of transporting damaged or aging cellular components into lysosomes for digestion and degradation. Accumulating evidence implies that autophagy is a key factor in tumor progression. The aim of this study was to determine a panel of novel autophagy-related prognostic markers for liver cancer.MethodsWe conducted a comprehensive analysis of autophagy-related gene (ARG) expression profiles and corresponding clinical information based on The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. The univariate Cox proportional regression model was used to screen candidate autophagy-related prognostic genes. In addition, a multivariate Cox proportional regression model was used to identify five key prognostic autophagy-related genes (ATIC, BAX, BIRC5, CAPNS1, and FKBP1A), which were used to construct a prognostic signature. Real-time qPCR analysis was used to evaluate the expression levels of ARGs in 20 surgically resected HCC samples and matched tumor-adjacent normal tissue samples. In addition, the effect of FKBP1A on autophagy and tumor progression was determined by performing in vitro and in vivo experiments.ResultsBased on the prognostic signature, patients with liver cancer were significantly divided into high-risk and low-risk groups in terms of overall survival (OS). A subsequent multivariate Cox regression analysis indicated that the prognostic signature remained an independent prognostic factor for OS. The prognostic signature possessing a better area under the curve (AUC) displayed better performance in predicting the survival of patients with HCC than other clinical parameters. Furthermore, FKBP1A was overexpressed in HCC tissues, and knockdown of FKBP1A impaired cell proliferation, migration, and invasion through the PI3K/AKT/mTOR signaling pathway.ConclusionThis study provides a prospective biomarker for monitoring outcomes of patients with HCC.

Project description:BackgroundCervical cancer is the second leading cause of death in women 20-39 years old. Because coverage for cervical cancer screening is low, and the vaccination rate of human papillomavirus (HPV) is poor in some countries, potential markers to detect the disease at early stages are needed. E2F transcription factors (E2Fs) are a family of transcription factors that function in cell proliferation, differentiation, apoptosis, and tumorigenesis. As abnormal activation and regulation of E2Fs are related to tumor development and poor prognosis, we performed bioinformatic analyses and in vitro assays to evaluate the role of E2Fs in cervical cancer.MethodsTranscriptional expression of E2Fs was initially evaluated in silico using ONCOMINE and Gene Expression Profiling Interactive Analysis (GEPIA), followed by evaluation of E2F1/2/7/8 protein levels using immunohistochemistry in 88 patient tissues. E2F2 and E2F7 mRNA levels were measured by RT-qPCR. LinkedOmics and Metascape were used to predict functions of E2Fs, and in vitro experiments were performed to assess the tumorigenic role of E2F2 and E2F7.ResultsIn silico analysis showed that E2F1/2/7/8 were significantly overexpressed in cervical cancer, findings which were confirmed at the protein level using immunohistochemistry. Further, upregulation of E2F1/2/7/8 was associated with different clinicopathological prognostic factors, including positivity for lymph vessel invasion and deep invasion of cervical stroma. Increased expression of E2F1/2/7/8 was also related to shorter overall survival (OS) and disease-free survival (DFS) in patients with cervical cancer. Using multivariate analysis, we confirmed E2F1/2/7/8 as independent prognostic factors for shorter OS of patients with cervical cancer. Finally, in vitro experiments showed that E2F2 and E2F7 are involved in cell proliferation and migration and cell cycle regulation in both HPV-positive and HPV-negative cervical cancer cells.ConclusionsE2F1/2/7/8 may be prognostic biomarkers for survival of patients with cervical cancer. E2F2 and E2F7 are involved in cell proliferation, migration, and cell cycle in both HPV-positive and HPV-negative cervical cancer cells.

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Transcriptional expressions of Chromobox 1/2/3/6/8 as independent indicators for survivals in hepatocellular carcinoma patients.

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Transcriptional expressions of Chromobox 1/2/3/6/8 as independent indicators for survivals in hepatocellular carcinoma patients.

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