A panel of differentially methylated regions enable prognosis prediction for colorectal cancer

e23007 Background: Over the past 20 years, the number of deaths from colorectal cancer (CRC) increased by 46% worldwide: every year more than 1 million people are diagnosed with this pathology. Proteomic studies using protein microarrays are a very attractive strategy for the screening of new highly specific biomarkers which can improve prognosis prediction of CRC. We performed a screening proteomic study to find new informative biomarkers for metastatic and non-metastatic colorectal cancer which can be further used in routine histochemical studies. Methods: The samples of tumor and non-tumor tissues of 20 patients with histologically confirmed adenocarcinoma of the colon were studied. Extraction, labeling and hybridization of proteins on the slide containing 224 antibodies for key cellular proteins were performed using the Panorama Antibody Microarray - Cell Signaling Kit, and the GenePix 4100A scanner was used for scanning. The data were analyzed using GenePixTMPro 6.0. Results: We revealed a significant (p < 0.05) increase in expression of such proteins as C-myc, SMAD4, PCAF, Adaptin (b1 + b2), FAK Phospho (pY577), PKC g and Phospho-Pyk2 (pY579/580) by 2.1; 1.5; 1.5; 1.5; 2.7 and 1.6 times, respectively, in tumor tissue of patients with metastatic colorectal cancer compared to non-tumor colon tissues. A significant increase (p < 0.05) in expression of proteins NGFR p75 (Nerve Growth Factor Receptor) by 3.8 times and Phospho-Ta (pS199 / 202) by 1.9 times was found in tumor tissue of patients with non-metastatic CRC in comparison with non-tumor colon tissue. Conclusions: The study showed changes in proteomic profile of malignant colon tissue, and proteomic profile differed significantly in tumor tissues of patients with metastatic and non-metastatic cancer. We found changes in expression of 9 proteins, differential in each group of patients (with metastatic and non-metastatic CRC). These proteins have a high potential as biomarkers for CRC prognosis prediction.

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A long non-coding RNA signature to improve prognosis prediction of colorectal cancer

Oncotarget ◽

10.18632/oncotarget.1895 ◽

2014 ◽

Vol 5 (8) ◽

pp. 2230-2242 ◽

Cited By ~ 108

Author(s):

Ye Hu ◽

Hao-Yan Chen ◽

Chen-Yang Yu ◽

Jie Xu ◽

Ji-Lin Wang ◽

...

Keyword(s):

Colorectal Cancer ◽

Prognosis Prediction ◽

Non Coding Rna ◽

Long Non Coding Rna ◽

Rna Signature

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Expression profile analysis of two antisense lncRNAs to improve prognosis prediction of colorectal adenocarcinoma

Cancer Cell International ◽

10.1186/s12935-019-1000-1 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 6

Author(s):

Milad Shademan ◽

Azam Naseri Salanghuch ◽

Khadijeh Zare ◽

Morteza Zahedi ◽

Mohammad Ali Foroughi ◽

...

Keyword(s):

Colorectal Cancer ◽

Expression Profile ◽

Antisense Rna ◽

Advanced Adenoma ◽

Low Grade ◽

Antisense Transcripts ◽

Expression Levels ◽

Prognosis Prediction ◽

Wide Range ◽

Antisense Lncrnas

Abstract Background Long noncoding RNAs (lncRNAs) are involved in different pathogenesis pathways including cancer pathogenesis. The adenoma-carcinoma pathway in colorectal cancer may involve the aberrant and variable gene expression of regulatory RNAs. This study was conducted to analyse the expression and prognosis prediction ability of two natural antisense transcripts, protein kinase C theta antisense RNA 1 (PRKCQ-AS1), and special AT-rich sequence binding protein 1 antisense RNA 1 (SATB1-AS1) in colorectal low-grade adenoma, advanced adenoma, and adenocarcinomas. Methods In this study, from two RNA-seq analyses of CCAT1-ko cells and colorectal carcinoma biopsies having diminished and increased levels of CCAT1 transcription, respectively, we nominated two antisense lncRNAs of PRKCQ-AS1 and SATB1-AS1. Samples from colorectal low-grade adenomas, advanced adenomas, adenocarcinomas, and adjacent tissue were subjected to RT-qPCR to determine the expression of PRKCQ-AS1, SATB1-AS1 along with colon cancer-associated transcript 1 (CCAT1) and cMYC. In addition, we used different bioinformatics analyses and webservers (including GEPIA 2, TCGA, and CancerMine) to elucidate the prognosis prediction value, the expression correlation of sense–antisense pair of genes, and the expression profile of these antisense transcripts at the presence or absence of mutations in the driver genes, or the corresponding sense genes. Results PRKCQ-AS1 showed a wide range of expression levels in colorectal adenoma, advanced adenoma, and adenocarcinoma. Upregulation of PRKCQ-AS1 was related to a significant decrease in survival of colorectal cancer (CRC) patients. The expression levels of PRKCQ-AS1 and PRKCQ were strong and significantly concordant in normal and cancerous colorectal tissues. While SATB1-AS1 showed a wide range of expression in colorectal adenoma, advanced adenoma, and adenocarcinoma as well, its expression was not related to a decrease in survival of CRC patients. The expression levels of SATB1-AS1 and SATB1 (the sense gene) were not strong in normal colorectal tissues. In addition, where SATB1 gene was mutated, the expression of SATB1-AS1 was significantly downregulated. Conclusions We found the expression of PRKCQ-AS1 and SATB1-AS1 at a given stage of CRC very variable, and not all biopsy samples showed the increased expression of these antisense transcripts. PRKCQ-AS1 in contrast to SATB1-AS1 showed a significant prognostic value. Since a significantly concordant expression was observed for SATB1-AS1 and SATB1 in only cancerous, and for PRKCQ-AS1 and PRKCQ in both normal and cancerous colorectal tissues, it can be concluded that common mechanisms may regulate the expression of these sense and antisense genes.

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