Alteration of tumor suppressor BMP5 in sporadic colorectal cancer: a genomic and transcriptomic profiling based study

Chen, Erfei; Yang, Fangfang; He, Hongbin; Zhang, Wei; Xing, Jinliang; Zhu, Zijue; Jiang, Jingjing; Wang, Hua; Zhao, Xiaojuan; Liu, Ruitao; Lei, Lei; Dong, Jing; Pei, Yuchen; Yang, Ying; Pan, Junqiang; Zhang, Pan; Liu, Shuzhen; Du, Le; Zeng, Yuan

doi:10.1186/s12943-018-0925-7

Cited by 43 publications

(40 citation statements)

References 29 publications

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“…Downregulated ATP6V0D2 probably functions through increasing HIF-2α expression produced by macrophage to enhance tumor vascularization and growth [49]. Previous studies showed that an elevated expression of ATP6V0D2 was found in stomach cancer specimens, whereas the expression was reduced in the colorectal and renal cancer specimens, which confirmed our findings [50,51]. But so far, as for the specific mechanism between ATP6V0D2 and ccRCC, there has been no research reported yet.…”

Section: Discussionsupporting

confidence: 88%

Construction of a novel gene-based model for prognosis prediction of clear cell renal cell carcinoma

et al. 2020

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Background: Clear cell renal cell carcinoma (ccRCC) comprises the majority of kidney cancer death worldwide, whose incidence and mortality are not promising. Identifying ideal biomarkers to construct a more accurate prognostic model than conventional clinical parameters is crucial.Methods: Raw count of RNA-sequencing data and clinicopathological data were acquired from The Cancer Genome Atlas (TCGA). Tumor samples were divided into two sets. Differentially expressed genes (DEGs) were screened in the whole set and prognosis-related genes were identified from the training set. Their common genes were used in LASSO and best subset regression which were performed to identify the best prognostic 5 genes. The gene-based risk score was developed based on the Cox coefficient of the individual gene. Time-dependent receiver operating characteristic (ROC) and Kaplan-Meier (KM) survival analysis were used to assess its prognostic power. GSE29609 dataset from GEO (Gene Expression Omnibus) database was used to validate the signature. Univariate and multivariate Cox regression were performed to screen independent prognostic parameters to construct a nomogram. The predictive power of the nomogram was revealed by time-dependent ROC curves and the calibration plot and verified in the validation set. Finally, Functional enrichment analysis of DEGs and 5 novel genes were performed to suggest the potential biological pathways.Results: PADI1, ATP6V0D2, DPP6, C9orf135 and PLG were screened to be significantly related to the prognosis of ccRCC patients. The risk score effectively stratified the patients into high-risk group with poor overall survival (OS) based on survival analysis. AJCC-stage, age, recurrence and risk score were regarded as independent prognostic parameters by Cox regression analysis and were used to construct a nomogram. Time-dependent ROC curves showed the nomogram performed best in 1-, 3-and 5-year survival predictions compared with AJCC-stage and risk score in validation sets. The calibration plot showed good agreement of the nomogram between predicted and observed outcomes. Functional enrichment analysis suggested several enriched biological pathways related to cancer. Conclusions:In our study, we constructed a gene-based model integrating clinical prognostic parameters to predict prognosis of ccRCC well, which might provide a reliable prognosis assessment tool for clinician and aid treatment decision-making in the clinic. © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article' s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article'

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Section: Discussionsupporting

confidence: 88%

Construction of a novel gene-based model for prognosis prediction of clear cell renal cell carcinoma

et al. 2020

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“…In the digestive system, BMP-5 plays similar roles in both colorectal cancer (CRC) and pancreatic cancer. The loss of BMP-5 expression takes place as an early event in CRC where BMP-5 may dysregulate E-cadherin and then trigger tumor initiation and development [61]. Also, miR32 may target BMP-5 to help CRC development [62].…”

Section: Discussionmentioning

confidence: 99%

Utilizing Experimental Mouse Model to Identify Effectors of Hepatocellular Carcinoma Induced by HBx Antigen

Yang

Chen

et al. 2020

Cancers

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Hepatocellular carcinoma (HCC) is among the ten most commonly diagnosed cancers and the fourth leading cause of cancer-related death. Patients with hepatitis B virus (HBV) infection are prone to developing chronic liver diseases (i.e., fibrosis and cirrhosis), and the HBV X antigen plays an important role in the development of HCC. The difficulty in detecting HCC at the early stages is one of the main reasons that the death rate approximates the incidence rate. The regulators controlling the downstream liver protein expression from HBV infection are unclear. Mass spectrometric techniques and customized programs were used to identify differentially expressed proteins which may be involved in the development of liver fibrosis and HCC progression in hepatitis B virus X protein transgenic mice (HBx mice). FSTL1, CTSB, and TGF-β enhanced the signaling pathway proteins during the pathogenesis of HBx. Missing proteins can be essential in cell growth, differentiation, Cancers 2020, 12, 409 2 of 32 apoptosis, migration, metastasis or angiogenesis. We found that LHX2, BMP-5 and GDF11 had complex interactions with other missing proteins and BMP-5 had both tumor suppressing and tumorigenic roles. BMP-5 may be involved in fibrosis and tumorigenic processes in the liver. These results provide us an understanding of the mechanism of HBx-induced disorders, and may serve as molecular targets for liver treatment.

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“…Total DNA was isolated using the QIAamp Tissue Kit (Qiagen, Dusseldorf, CA). Three cases of fresh sCRC tissue samples were used for whole‐exome sequencing (data were shown in Chen's study), while the matched blood samples were used to validate mutations present in their own cancer tissue samples. Fifty cases of FFPE sCRC tissue samples were used for the deep sequencing of SARDH exons (primers used as shown in Table S2), while their adjacent normal tissue samples were used to validate mutations present in their own cancer tissue samples.…”

Section: Methodsmentioning

confidence: 99%

Alteration of the tumor suppressor SARDH in sporadic colorectal cancer: A functional and transcriptome profiling‐based study

Chen

Lei

et al. 2019

Molecular Carcinogenesis

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Sporadic colorectal cancer (sCRC) is one of the leading causes of cancer death worldwide. As a highly heterogeneous complex disease, the currently reported classical genetic markers for sCRC, including APC, KRAS, BRAF, and TP53 gene mutations and epigenetic alterations, can explain only some sCRC patients. Here, we first reported a deleterious c.551C>T mutation in SARDH in sCRC. SARDH was identified as a novel tumor suppressor gene and was abnormally decreased in sCRC at both the transcriptional and the translational level. SARDH mRNA levels were also down‐regulated in oesophageal cancer, lung cancer, liver cancer, and pancreatic cancer in the TCGA database. SARDH overexpression inhibited the proliferation, migration, and invasion of CRC cell lines, whereas its depletion improved these processes. SARDH overexpression was down‐regulated in multiple pathways, especially in the chemokine pathway. The SARDH transcript level was positively correlated with the methylation states of CXCL1 and CCL20. Therefore, we concluded that SARDH depletion is involved in the development of sCRC.

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Alteration of tumor suppressor BMP5 in sporadic colorectal cancer: a genomic and transcriptomic profiling based study

Cited by 43 publications

References 29 publications

Construction of a novel gene-based model for prognosis prediction of clear cell renal cell carcinoma

Construction of a novel gene-based model for prognosis prediction of clear cell renal cell carcinoma

Utilizing Experimental Mouse Model to Identify Effectors of Hepatocellular Carcinoma Induced by HBx Antigen

Alteration of the tumor suppressor SARDH in sporadic colorectal cancer: A functional and transcriptome profiling‐based study

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