Integrated TCGA and GEO analysis showed that SMAD7 is an independent prognostic factor for lung adenocarcinoma

Dai, Zhou-Tong; Wang, Jun; Zhao, Kai; Yuan, Xiang; Li, Jia Peng; Zhang, Huimin; Peng, Zi-Tan; Liao, Xing

doi:10.1097/md.0000000000022861

Cited by 6 publications

(4 citation statements)

References 43 publications

(43 reference statements)

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“…The third pathway identified was TGF-b through the overexpression of the SMAD9 gene. This gene belongs to the SMAD superfamily (Drosophila mothers against decapentaplegic protein) made up of important cytokines in the TGF-b family (32). SMAD9 overexpression is associated with the prevalence of hamartomatous polyposis and is a prognostic factor for lung cancer (33,34).…”

Section: Discussionmentioning

confidence: 99%

A 4-Gene Signature Associated With Recurrence in Low- and Intermediate-Risk Endometrial Cancer

et al. 2021

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BackgroundThe molecular profile of endometrial cancer has become an important tool in determining patient prognosis and their optimal adjuvant treatment. In addition to The Cancer Genome Atlas (TCGA), simpler tools have been developed, such as the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE). We attempted to determine a genetic signature to build a recurrence risk score in patients diagnosed with low- and intermediate-risk endometrial cancer.MethodsA case-control study was conducted. The eligible patients were women diagnosed with recurrence low- and intermediate-risk endometrial cancer between January 2009 and December 2014 at a single institution; the recurrence patients were matched to two nonrecurrence patients with the same diagnosis by age and surgical staging. Following RNA isolation of 51 cases, 17 recurrence and 34 nonrecurrence patients, the expression profile was determined using the nCounter® PanCancer Pathways Panel, which contains 770 genes.ResultsThe expression profile was successfully characterized in 49/51 (96.1%) cases. We identified 12 genes differentially expressed between the recurrence and nonrecurrence groups. The ROC curve for each gene was generated, and all had AUCs higher than 0.7. After backward stepwise logistic regression, four genes were highlighted: FN1, DUSP4, LEF1, and SMAD9. The recurrence risk score was calculated, leading to a ROC curve of the 4-gene model with an AUC of 0.93, sensitivity of 100%, and specificity of 72.7%.ConclusionWe identified a four-gene signature that may be associated with recurrence in patients with low- and intermediate-risk endometrial cancer. This finding suggests a new prognostic factor in this poorly explored group of patients with endometrial cancer.

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Section: Discussionmentioning

confidence: 99%

A 4-Gene Signature Associated With Recurrence in Low- and Intermediate-Risk Endometrial Cancer

et al. 2021

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“…Clinical information was obtained from TCGA database. Gene expression (CDK1, CDK2, CDK4, and CDK6) was determined using R and Perl software ( 17 ). Gene expression levels of different tumor stages and survival rate calculations were processed by Gene Expression Profiling Interactive Analysis (GEPIA) ( 18 ).…”

Section: Methodsmentioning

confidence: 99%

Identification of the Effects of Chondroitin Sulfate on Inhibiting CDKs in Colorectal Cancer Based on Bioinformatic Analysis and Experimental Validation

Zhou

Morita

et al. 2021

Front. Oncol.

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With a high occurrence rate and high mortality, the treatment of colorectal cancer (CRC) is increasingly attracting the attention of scholars. Hub genes that determine the phenotypes of CRC become essential for targeted therapy. In the present study, the importance of cyclin-dependent kinases (CDKs) on the occurrence of CRC was identified by data mining of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The results showed that the gene expression levels of CDK1, CDK4, and CDK6 were obviously changed in different stages of CRC. Among the CDKs, CDK4 was suggested as an independent risk factor for CRC based on Cox analysis. Furthermore, chondroitin sulfate (CS), a kind of dietary supplement to treat osteoarthritis, was predicted to treat CRC based on its chemical structure and GEO datasets. Cell assay experiments with the human CRC cell line HCT-116 also verified this prediction. CS inhibited the gene and protein expression levels of CDKs and increased the ratios of apoptotic or dead HCT-116 cells by regulating mitogen-activated protein (MAP) kinase pathways. Our data highlight the essential roles of CDKs in CRC carcinogenesis and the effects of CS on treating CRC, both of which will contribute to the future CRC treatment.

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“…Dysregulation of SMAD7 expression by a post-transcriptional regulation leads to aberrant activation of TGF-β signaling pathway, and such a scenario has been found in the malignant progression of multiple cancer types 8 – 12 . Interestingly, the mRNA level of SMAD7 was found markedly lower in LAD samples than that in paired adjacent normal tissues, and lower SMAD7 level correlated with poor prognosis of LAD patients 13 – 15 . In such a context, therefore, better understanding of the underlying mechanism of restraining SMAD7 transcription in LAD may implicate promising therapeutic targets or prognostic biomarkers for metastatic LAD.…”

Section: Introductionmentioning

confidence: 95%

PHF14 enhances DNA methylation of SMAD7 gene to promote TGF-β-driven lung adenocarcinoma metastasis

Tian

Liu

et al. 2023

Cell Discov

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Aberrant activation of TGF-β signaling plays a pivotal role in cancer metastasis and progression. However, molecular mechanisms underlying the dysregulation of TGF-β pathway remain to be understood. Here, we found that SMAD7, a direct downstream transcriptional target and also a key antagonist of TGF-β signaling, is transcriptionally suppressed in lung adenocarcinoma (LAD) due to DNA hypermethylation. We further identified that PHF14 binds DNMT3B and serves as a DNA CpG motif reader, recruiting DNMT3B to the SMAD7 gene locus, resulting in DNA methylation and transcriptional suppression of SMAD7. Our in vitro and in vivo experiments showed that PHF14 promotes metastasis through binding DNMT3B to suppress SMAD7 expression. Moreover, our data revealed that PHF14 expression correlates with lowered SMAD7 level and shorter survival of LAD patients, and importantly that SMAD7 methylation level of circulating tumor DNA (ctDNA) can potentially be used for prognosis prediction. Together, our present study illustrates a new epigenetic mechanism, mediated by PHF14 and DNMT3B, in the regulation of SMAD7 transcription and TGF-β-driven LAD metastasis, and suggests potential opportunities for LAD prognosis.

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Integrated TCGA and GEO analysis showed that SMAD7 is an independent prognostic factor for lung adenocarcinoma

Abstract: Supplemental Digital Content is available in the text

Cited by 6 publications

References 43 publications

A 4-Gene Signature Associated With Recurrence in Low- and Intermediate-Risk Endometrial Cancer

A 4-Gene Signature Associated With Recurrence in Low- and Intermediate-Risk Endometrial Cancer

Identification of the Effects of Chondroitin Sulfate on Inhibiting CDKs in Colorectal Cancer Based on Bioinformatic Analysis and Experimental Validation

PHF14 enhances DNA methylation of SMAD7 gene to promote TGF-β-driven lung adenocarcinoma metastasis

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