Su1683 ASSOCIATION BETWEEN SESSILE SERRATED ADENOMA/POLYP AND MICROSATELLITE INSTABILITY-HIGH COLORECTAL CANCER: A BIOINFORMATIC ANALYSIS OF COMPREHENSIVE GENE EXPRESSION

The dysfunction of the DNA mismatch repair system results in microsatellite instability (MSI). MSI plays a central role in the development of multiple human cancers. In colon cancer, despite being associated with resistance to 5-fluorouracil treatment, MSI is a favourable prognostic marker. In gastric and endometrial cancers, its prognostic value is not so well established. Nevertheless, recognising the MSI tumours may be important for predicting the therapeutic effect of immune checkpoint inhibitors. Several gene expression signatures were trained on microarray data sets to understand the regulatory mechanisms underlying microsatellite instability in colorectal cancer. A wealth of expression data already exists in the form of microarray data sets. However, the RNA-seq has become a routine for transcriptome analysis. A new MSI gene expression signature presented here is the first to be valid across two different platforms, microarrays and RNA-seq. In the case of colon cancer, its estimated performance was (i) AUC = 0.94, 95% CI = (0.90 – 0.97) on RNA-seq and (ii) AUC = 0.95, 95% CI = (0.92 – 0.97) on microarray. The 25-gene expression signature was also validated in two independent microarray colon cancer data sets. Despite being derived from colorectal cancer, the signature maintained good performance on RNA-seq and microarray gastric cancer data sets (AUC = 0.90, 95% CI = (0.85 – 0.94) and AUC = 0.83, 95% CI = (0.69 – 0.97), respectively). Furthermore, this classifier retained high concordance even when classifying RNA-seq endometrial cancers (AUC = 0.71, 95% CI = (0.62 – 0.81). These results indicate that the new signature was able to remove the platform-specific differences while preserving the underlying biological differences between MSI/MSS phenotypes in colon cancer samples.

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Microsatellite instability, MMR gene expression and proliferation kinetics in colorectal cancer with famillial predisposition

World Journal of Gastroenterology ◽

10.3748/wjg.v6.i6.902 ◽

2000 ◽

Vol 6 (6) ◽

pp. 902 ◽

Cited By ~ 10

Author(s):

Bao Ping Wu

Keyword(s):

Gene Expression ◽

Colorectal Cancer ◽

Microsatellite Instability ◽

Proliferation Kinetics

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A Novel Pit Pattern Identifies the Precursor of Colorectal Cancer Derived From Sessile Serrated Adenoma

The American Journal of Gastroenterology ◽

10.1038/ajg.2011.457 ◽

2012 ◽

Vol 107 (3) ◽

pp. 460-469 ◽

Cited By ~ 106

Author(s):

Tomoaki Kimura ◽

Eiichiro Yamamoto ◽

Hiro-o Yamano ◽

Hiromu Suzuki ◽

Seiko Kamimae ◽

...

Keyword(s):

Colorectal Cancer ◽

Pit Pattern ◽

Sessile Serrated Adenoma ◽

Serrated Adenoma

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Identification of the miRNA signature and key genes in colorectal cancer lymph node metastasis

Cancer Cell International ◽

10.1186/s12935-021-02058-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Xi Wang ◽

Guangyu Gao ◽

Zhengrong Chen ◽

Zhihao Chen ◽

Mingxiao Han ◽

...

Keyword(s):

Gene Expression ◽

Colorectal Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Expression Profiles ◽

Bioinformatic Analysis ◽

The Cancer Genome Atlas ◽

Node Metastasis ◽

Novel Mirna ◽

Potential Biomarker

Abstract Background Because its metastasis to the lymph nodes are closely related to poor prognosis, miRNAs and mRNAs can serve as biomarkers for the diagnosis, prognosis, and therapy of colorectal cancer (CRC). This study aimed to identify novel gene signatures in the lymph node metastasis of CRC. Methods GSE56350, GSE70574, and GSE95109 datasets were downloaded from the Gene Expression Omnibus (GEO) database, while data from 569 colorectal cancer cases were also downloaded from The Cancer Genome Atlas (TCGA) database. Differentially expressed miRNAs (DE-miRNAs) were calculated using R programming language (Version 3.6.3), while gene ontology and enrichment analysis of target mRNAs were performed using FunRich (http://www.funrich.org). Furthermore, the mRNA–miRNA network was constructed using Cytoscape software (Version 3.8.0). Gene expression levels were verified using the GEO datasets. Similarly, quantitative real-time PCR (qPCR) was used to examine expression profiles from 20 paired non-metastatic and metastatic lymph node tissue samples obtained from patients with CRC. Results In total, five DE-miRNAs were selected, and 34 mRNAs were identified after filtering the results. Moreover, two key miRNAs (hsa-miR-99a, hsa-miR-100) and one gene (heparan sulfate-glucosamine 3-sulfotransferase 2 [HS3ST2]) were identified. The GEO datasets analysis and qPCR results showed that the expression of key miRNA and genes were consistent with that obtained from the bioinformatic analysis. A novel miRNA–mRNA network capable of predicting the prognosis and confirmed experimentally, hsa-miR-99a-HS3ST2-hsa-miR-100, was found after expression analysis in metastasized lymph node tissue from CRC samples. Conclusion In summary, miRNAs and genes with potential as biomarkers were found and a novel miRNA–mRNA network was established for CRC lymph node metastasis by systematic bioinformatic analysis and experimental validation. This network may be used as a potential biomarker in the development of lymph node metastatic CRC.

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Significant difference of c-type lectin-like receptor 2 between colorectal cancer and polyp subgroups

Cancer Biomarkers ◽

10.3233/cbm-200734 ◽

2021 ◽

pp. 1-7

Author(s):

Meng-Lin Zhang ◽

Wen-Juan Huang ◽

Chen-Xi Yue ◽

Ming-Ming Li ◽

Na Li ◽

...

Keyword(s):

Colorectal Cancer ◽

Hyperplastic Polyp ◽

Colorectal Polyps ◽

Curve Analysis ◽

Enzyme Linked Immunosorbent Assay ◽

Sessile Serrated Adenoma ◽

Roc Curve Analysis ◽

Serrated Adenoma ◽

Node Metastasis ◽

Significant Difference

BACKGROUND: Platelets play a key role in tumor progression and metastasis. C-type lectin-like receptor 2 (CLEC-2) is the receptor expressed on platelets and the marker of platelet activation. OBJECTIVE: This study aims to determine whether soluble CLEC-2 levels differ between patients with benign colorectal polyps and those with colorectal cancer (CRC). METHODS: We measured plasma soluble CLEC-2 by enzyme-linked immunosorbent assay in 150 patients with colorectal polyps, 150 CRC patients without metastasis, 150 CRC liver metastasis, and 150 control subjects. RESULTS: The CRC patients had higher soluble CLEC-2 levels than patients with colorectal polyps (p< 0.001). Moreover, CRC patients with liver metastases displayed higher CLEC-2 levels than those in CRC patients without metastases (p< 0.001). In the CRC patients, CLEC-2 levels were correlated with lymph node metastasis and advanced stage. In the patients with polyps, there was a significant difference in CLEC-2 levels among patients with hyperplastic polyp, sessile serrated adenoma, and traditional serrated adenoma (p< 0.001). The ROC curve analysis revealed CLEC-2 had an optimal sensitivity of 77.3% and specificity of 94.6% for the screening of CRC, and sensitivity of 71.0% and specificity of 76.7% for the differential diagnosis of colorectal polyps and CRC. CONCLUSIONS: CRC patients have higher CLEC-2 levels than patients with colorectal polyps and healthy controls. Moreover, there is a significant difference in CLEC-2 levels among polyp subtypes. Further research is warranted.

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