Dataset Information

Tumor-suppressive role of Smad ubiquitination regulatory factor 2 in patients with colorectal cancer.

ABSTRACT: Smad ubiquitination regulatory factor 2 (Smurf2) plays various roles in cancer progression. However, the correlation between Smurf2 and clinical outcomes has not been determined in patients diagnosed with colorectal cancer and colorectal liver metastases. We analyzed 66 patients with colorectal cancer who developed liver metastases. Smurf2 expression was assessed using immunohistochemical analysis of primary and metastatic liver tumors. High Smurf2 expression in both primary and metastatic tumors was significantly associated with longer overall survival time and time to surgical failure. Multivariate analyses revealed that low Smurf2 expression in primary tumors was an independent predictor of poor prognosis. In vitro experiments using colon cancer cell lines demonstrated that short interfering RNA knockdown of Smurf2 increased cell migration and tumor sphere formation. Western blot analyses revealed that Smurf2 knockdown increased the protein expression of epithelial cell adhesion molecule (EpCAM). Thus, in summary, high Smurf2 expression in cancer cells was found to be an independent predictor of better prognosis in patients with primary colorectal cancer and consequent liver metastases. The tumor-suppressive role of Smurf2 was found to be associated with cell migration and EpCAM expression; hence, Smurf2 can be considered a positive biomarker of cancer stem cell-like properties.

SUBMITTER: Sato N

PROVIDER: S-EPMC8971512 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Tumor-suppressive role of Smad ubiquitination regulatory factor 2 in patients with colorectal cancer.

Sato Nami N Sakai Nozomu N Furukawa Katsunori K Takayashiki Tsukasa T Kuboki Satoshi S Takano Shigetsugu S Ohira Gaku G Miyauchi Hideaki H Matsubara Hisahiro H Ohtsuka Masayuki M

Scientific reports 20220331 1

Smad ubiquitination regulatory factor 2 (Smurf2) plays various roles in cancer progression. However, the correlation between Smurf2 and clinical outcomes has not been determined in patients diagnosed with colorectal cancer and colorectal liver metastases. We analyzed 66 patients with colorectal cancer who developed liver metastases. Smurf2 expression was assessed using immunohistochemical analysis of primary and metastatic liver tumors. High Smurf2 expression in both primary and metastatic tumor ...[more]

PMID: 35361871

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Project description:BackgroundSince interferon regulatory factor (IRF) family functions in immune response to viral infection, its role in colorectal cancer (CRC) has not been inspected before. This study tries to investigate members of IRF family using bioinformatics approaches in aspect of differential expressions, biological function, tumor immune infiltration and clinical prognostic value for patients with CRC.MethodsTranscriptome profiles data, somatic mutations and clinical information of CRC were obtained from COAD/READ dataset of The Cancer Genome Atlas (TCGA) as a training set. Gene expression data (GSE17536 and GSE39582) were downloaded from the Gene Expression Omnibus as a validating set. A random forest algorithm was used to score the risk for every case. Analyzing gene and function enrichment, constructing protein-protein interaction and noncoding RNA network, identifying hub-gene, characterizing tumor immune infiltration, evaluating differences in tumor mutational burden (TMB) and sensitivity to chemotherapeutics or immunotherapy were performed by a series of online tools and R packages. Immunohistochemical (IHC) examinations were carried out validation in tissue samples.ResultsPrincipal-component analysis (PCA) suggested that the transcript expression levels of nine members of IRF family differed between normal colorectum and CRC. The risk score constructed by IRF family not only acted as an independent factor for predicting survival in CRC patients with different biological processes, signaling pathways and TMB, but also indicated different immunotherapy response with diverse immune and stromal cells infiltration. IRF3 and IRF7 were upregulated in CRC and suggested a shorter survival time in patients with CRC. Differentially expressed members of IRF family exhibited varying degrees of immune cell infiltration. IHC analysis showed a positive association between IRF3 and IRF7 expression and tumor-infiltrating immune cells, including CD4+ T cell and CD68+ macrophages.ConclusionsOn account of differential expression, IRF family members can help to predict both response to immunotherapy and clinical prognosis of patients with CRC. Our bioinformatic investigation not only gives a preliminary picture of the genetic features as well as tumor microenvironment, but it may provide a clue for further experimental exploration and verification on IRF family members in CRC.

Dataset Information

Tumor-suppressive role of Smad ubiquitination regulatory factor 2 in patients with colorectal cancer.

Publications

Tumor-suppressive role of Smad ubiquitination regulatory factor 2 in patients with colorectal cancer.

Similar Datasets

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