SMOC2, an intestinal stem cell marker, is an independent prognostic marker associated with better survival in colorectal cancers

Jang, Bo Gun; Kim, Hye Sung; Bae, Jeong Mo; Kim, Woo Ho; Kim, Heung Up; Kang, Gyeong Hoon

doi:10.1038/s41598-020-71643-1

Cited by 23 publications

(20 citation statements)

References 25 publications

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“…A volcano plot for strongly up/downregulated genes in the iHUCO stem cell sub-population consistently showed suppression of Lgr5-expressing cells (Supplementary Fig. 5d ) whereas genes such as SMOC2 78 , which promotes matrix assembly and cell adhesiveness, were overexpressed. Our in situ hybridization for Lgr5 confirmed that this stem cell marker was suppressed in iHUCOs (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 91%

Induced organoids derived from patients with ulcerative colitis recapitulate colitic reactivity

Sarvestani

Signs

et al. 2021

Nat Commun

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The pathogenesis of ulcerative colitis (UC), a major type of inflammatory bowel disease, remains unknown. No model exists that adequately recapitulates the complexity of clinical UC. Here, we take advantage of induced pluripotent stem cells (iPSCs) to develop an induced human UC-derived organoid (iHUCO) model and compared it with the induced human normal organoid model (iHNO). Notably, iHUCOs recapitulated histological and functional features of primary colitic tissues, including the absence of acidic mucus secretion and aberrant adherens junctions in the epithelial barrier both in vitro and in vivo. We demonstrate that the CXCL8/CXCR1 axis was overexpressed in iHUCO but not in iHNO. As proof-of-principle, we show that inhibition of CXCL8 receptor by the small-molecule non-competitive inhibitor repertaxin attenuated the progression of UC phenotypes in vitro and in vivo. This patient-derived organoid model, containing both epithelial and stromal compartments, will generate new insights into the underlying pathogenesis of UC while offering opportunities to tailor interventions to the individual patient.

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Section: Resultsmentioning

confidence: 91%

Induced organoids derived from patients with ulcerative colitis recapitulate colitic reactivity

Sarvestani

Signs

et al. 2021

Nat Commun

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“…Higher expression of TEADs, as well as association with poor patient survival, have been observed in many cancers including CRC [52,53]. On the other hand, the target gene SMOC2 was recently shown to be a favorable prognostic biomarker for better clinical outcomes in a large cohort of CRC patients [54]. Therefore, the MethReg prediction that transcription factor TEAD3 suppresses target gene SMOC2 is consistent with the oncogenic role of TEAD3 and the favorable prognostic potential of SMOC2.…”

Section: Simulation Analysismentioning

confidence: 56%

MethReg: estimating the regulatory potential of DNA methylation in gene transcription

Silva

Young

Martin

et al. 2021

Preprint

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Epigenome-wide association studies (EWAS) often detect a large number of differentially methylated sites or regions, many are located in distal regulatory regions. To further prioritize these significant sites, there is a critical need to better understand the functional impact of CpG methylation. Recent studies demonstrated CpG methylation-dependent transcriptional regulation is a widespread phenomenon. Here we present MethReg, an R/Bioconductor package that analyzes matched DNA-methylation and gene-expression data, along with external transcription factor (TF) binding information, to evaluate, prioritize, and annotate CpG sites with high regulatory potential. By simultaneous modeling three key elements that contribute to gene transcription (CpG methylation, target gene expression and TF activity), MethReg identifies TF-target gene associations that are present only in a subset of samples with high (or low) methylation levels at the CpG that influences TF activities, which can be missed in analyses that use all samples. Using real colorectal cancer and Alzheimer's disease datasets, we show MethReg significantly enhances our understanding of the regulatory roles of DNA methylation in complex diseases.

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“…The correlation between SMOC2 and diseases has been widely reported. Jang et al[34] reported that SMOC2 is a tumor suppressor in colorectal cancer and can elevate the expression of SMOC2 and suppress cell migration, colony and sphere formation. However, Lu et al[35] reported on the suppression function in colon carcinoma invasion and migration of ARNTL2 via decreased SMOC2-EMT activity.…”

Section: Discussionmentioning

confidence: 99%

Molecular classification reveals the diverse genetic features and prognosis of gastric cancer: a multi-omics consensus ensemble clustering

Wang

et al. 2021

Preprint

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Background: Gastric cancer (GC) is the fifth most common tumor around the world, it is necessary to reveal novel molecular subtypes to guide the selection of patients who may benefit from specific target therapy. Methods: Multi-omics data, including RNA-sequence of transcriptomics (mRNA, LncRNA, miRNA), DNA methylation and gene mutation of TCGA-STAD cohort was used for the clustering. Ten classical clustering algorithms were applied to recognize patients with different molecular features via the R package MOVICS. The activated signaling pathways were evaluated using the single-sample gene set enrichment analysis. The difference distribution of gene mutations, copy number alterations and tumor mutation burden was compared, and potential response to immunotherapy and chemotherapy was assessed as well. Results: Two molecular subtypes (CS1 and CS2) were recognized by ten clustering algorithms with further consensus ensembles. Patients in the CS1 group were found to contain a shorter average overall survival time (28.5 vs. 68.9 months, P = 0.016), and progression-free survival (19.0 vs. 63.9 months, P = 0.008) compared to the CS2 group. CS1 group contained more activation of extracellular associated biological process, while CS2 group displayed the activation of cell cycle associated pathways. The significantly higher total mutation numbers and neo antigens were observed in CS2 group, along with the specific mutation of TTN, MUC16 and ARID1A. Higher infiltration of immunocytes were also observed in CS2 group, reflected to the potential benefit from immunotherapy. Moreover, CS2 group also can response to 5-fluorouracil, cisplatin, and paclitaxel. The similar diverse of clinical outcome of CS1 and CS2 groups were successfully validation in external cohorts of GSE62254, GSE26253, GSE15459, and GSE84437. Conclusion: Novel insight into the GC subtypes was obtained via integrative analysis of five omics data by ten clustering algorithms, which can provide the idea to the clinical target therapy based on the specific molecular features.

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SMOC2, an intestinal stem cell marker, is an independent prognostic marker associated with better survival in colorectal cancers

Cited by 23 publications

References 25 publications

Induced organoids derived from patients with ulcerative colitis recapitulate colitic reactivity

Induced organoids derived from patients with ulcerative colitis recapitulate colitic reactivity

MethReg: estimating the regulatory potential of DNA methylation in gene transcription

Molecular classification reveals the diverse genetic features and prognosis of gastric cancer: a multi-omics consensus ensemble clustering

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