Bioinformatic analysis reveals in common genes between colorectal cancer and recurrent colorectal malignancy

Gene Reports ◽  
2021 ◽  
Vol 25 ◽  
pp. 101375
Author(s):  
Rasoul Nemati ◽  
Mehdi Valizadeh ◽  
Mehrdad Mohammadi ◽  
Atena Kamali
Cancers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 147 ◽  
Author(s):  
Carlo Capalbo ◽  
Francesca Belardinilli ◽  
Domenico Raimondo ◽  
Edoardo Milanetti ◽  
Umberto Malapelle ◽  
...  

The response of metastatic colorectal cancer (mCRC) to the first-line conventional combination therapy is highly variable, reflecting the elevated heterogeneity of the disease. The genetic alterations underlying this heterogeneity have been thoroughly characterized through omic approaches requiring elevated efforts and costs. In order to translate the knowledge of CRC molecular heterogeneity into a practical clinical approach, we utilized a simplified Next Generation Sequencing (NGS) based platform to screen a cohort of 77 patients treated with first-line conventional therapy. Samples were sequenced using a panel of hotspots and targeted regions of 22 genes commonly involved in CRC. This revealed 51 patients carrying actionable gene mutations, 22 of which carried druggable alterations. These mutations were frequently associated with additional genetic alterations. To take into account this molecular complexity and assisted by an unbiased bioinformatic analysis, we defined three subgroups of patients carrying distinct molecular patterns. We demonstrated these three molecular subgroups are associated with a different response to first-line conventional combination therapies. The best outcome was achieved in patients exclusively carrying mutations on TP53 and/or RAS genes. By contrast, in patients carrying mutations in any of the other genes, alone or associated with mutations of TP53/RAS, the expected response is much worse compared to patients with exclusive TP53/RAS mutations. Additionally, our data indicate that the standard approach has limited efficacy in patients without any mutations in the genes included in the panel. In conclusion, we identified a reliable and easy-to-use approach for a simplified molecular-based stratification of mCRC patients that predicts the efficacy of the first-line conventional combination therapy.


2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Chang-li Zhu ◽  
Xiaofeng Sha ◽  
Yuan Wang ◽  
Jin Li ◽  
Men-yan Zhang ◽  
...  

Circular RNAs (circRNAs) are a large class of endogenous noncoding RNAs that regulate gene expression and mainly function as microRNA sponges. This study aimed to explore the aberrant expression of circRNAs in colorectal cancer (CRC). Using a circRNA microarray, we identified 892 differentially expressed circRNAs between six pairs of CRC and adjacent paracancerous tissues. Among them, hsa_circ_0007142 was significantly upregulated. Further analysis in 50 CRC clinical samples revealed that hsa_circ_0007142 upregulation was associated with poor differentiation and lymphatic metastasis of CRC. Bioinformatic analysis and luciferase reporter assay showed that hsa_circ_0007142 targeted miR-103a-2-5p in CRC cells. Moreover, the silencing of hsa_circ_0007142 by siRNAs decreased the proliferation, migration, and invasion of HT-29 and HCT-116 cells. Taken together, these findings suggest that hsa_circ_0007142 is upregulated in CRC and targets miR-103a-2-5p to promote CRC.


2009 ◽  
Vol 56 (4) ◽  
pp. 113-119
Author(s):  
M.A. Lucic ◽  
I.S. Miucin-Vukadinovic ◽  
S.M. Lucic ◽  
K.M. Koprivek ◽  
M. Spirovski ◽  
...  

A wide spectrum of nowadays availible radiological and imaging methods in the diagnostic evaluation of patients with colorectal cancer enabled not only the improvement of primary colorectal malignancy detection, precise staging, regional involvement and metastatic spread assessment, but also the posttherapeutical estimation and follow- up. Having in mind that the exact diagnostic assessment of colorectal carcinoma by use of different imaging modalities still raises a lots of contradictories, in this report we have tried to present the possibilities of newer imaging techniques in the diagnostic evaluation of the patients with colorectal cancer.


2019 ◽  
Vol 39 (7) ◽  
Author(s):  
Ming-li Yang ◽  
Zhe Huang ◽  
Li-na Wu ◽  
Rong Wu ◽  
Han-xi Ding ◽  
...  

AbstractBackground: Single-nucleotide polymorphisms (SNPs) in lncRNAs could be biomarkers for susceptibility to colorectal cancer (CRC), but the association of PCAT1 polymorphisms and CRC susceptibility is yet to be studied. Methods: Five tagSNPs covering the PCAT1 gene were detected through Kompetitive Allele-Specific PCR among 436 CRC patients and 510 controls. An expression quantitative trait locus (eQTL) bioinformatic analysis was then performed. Results: In the present study, PCAT1 rs2632159 polymorphism increased CRC risk by 1.37-fold and 2.19-fold in the dominant and recessive models, respectively (P=0.040 and 0.041). When the CRC cases were divided into colon cancer and rectal cancer, we found that this polymorphism affected colon cancer risk under the dominant model (P=0.022, OR = 1.51) and affected rectal cancer susceptibility under the recessive model (P=0.009, OR = 3.03). A more pronounced effect was observed in the male subgroup in that PCAT1 rs2632159 SNP increased rectal cancer risk by 3.97-fold (P=0.017). When PCAT1 rs2632159 was present, epistatic effects were observed with rs1902432 and rs785005 (P=0.011 and 0.008, respectively). eQTL analysis showed that rs2632159 could influence binding with the transcription factors EBF, LUN-1, and TCF12. Conclusion:PCAT1 rs2632159 SNP could be a biomarker for CRC risk. And the rs1902432 SNP might only have potential to be a biomarker for colon cancer risk.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xi Wang ◽  
Guangyu Gao ◽  
Zhengrong Chen ◽  
Zhihao Chen ◽  
Mingxiao Han ◽  
...  

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.


2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Bin Deng ◽  
Xiu-Ping Liu ◽  
Xiong Wang

Objective. Thrombospondin 2 (THBS2) acts as oncogenic or tumor suppressive gene in diverse cancers. Here we studied the prognostic and immunological role of THBS2 in colorectal cancer (CRC) using bioinformatic analysis. Methods. The genetic and protein expression of THBS2 in CRC were explored across several databases, including ONCOMINE, GEPIA2, TIMER 2.0, UALCAN and HPA databases. Correlation between THBS2 expression and clinical features in CRC was assessed using UALCAN tool. Prognostic analysis was performed using GEPIA2 and PrognoScan. Immune infiltration correlation with THBS2 in CRC was investigated with TIMER 2.0 and TISIDB. THBS2 binding and correlated genes were analyzed using String, GEPIA2, and TIMER 2.0. Results. THBS2 was significantly higher in CRC across multiple databases. Age and histological subtype were correlated with THBS2 level. High THBS2 expression correlated with short overall and disease-free survival. THBS2 expression was positively correlated with immune infiltrates in CRC. Moreover, extracellular matrix structural constituent and organization, PI3K-Akt pathway, were involved in the functional mechanisms of THBS2. Conclusions. THBS2 correlates with poor prognosis and immune infiltration in CRC. THBS2 may act as a prognostic and immunological biomarker for CRC.


2021 ◽  
Vol 116 (1) ◽  
pp. S79-S79
Author(s):  
Chenyu Sun ◽  
John Pocholo W. Tuason ◽  
Na Hyun Kim ◽  
Chandur Bhan ◽  
Nikitha Manem ◽  
...  

2021 ◽  
Vol 1 (1) ◽  
pp. 14-31
Author(s):  
Dilara Fatma Akin Bali

Introduction: It has been aimed to analyze the role of pathogenic effects of mutation and expression anomalies occurring on diaphanous-related formin 1 (DIAPH1), WASP actin nucleation-promoting factor (WASP), myosin heavy chain 9 (MYH9), actinin alpha 1 (ACNT1), filamin A (FLNA), and tubulin beta 1 class VI (TUBB1), which are known as fundamental cellular skeleton proteins, on the development and progression of cancer via bioinformatic tools. Methods: The genome sequence and expression profiles of 594 Colorectal Cancer (CRC) patients were obtained via bioinformatic tools, which provide data for The Cancer Genome Atlas. The mutation patterns of six genes were determined in detail, and for the prediction of pathogenic properties of identified changes for CRC, Polymorphism Phenotyping v2, Screening for Non-Acceptable Polymorphisms, and the Catalogue Of Somatic Mutations In Can- cer were utilized. Apart from the mutation profile, the effects of existing mutations on messenger ribonucleic acid (mRNA) expression and survival were also identified. Moreover, the Search Tool for the Retrieval of Interacting Genes/Proteins network analysis was realized to further comprehend the functional relations of proteins in cellu- lar processes. Results: There have been 142 distinct point mutations, gene amplification, and deep deletions identified on DIAPH1, WAS, MYH9, ACNT1, FLNA, and TUBB1 genes. ACTN1 and FLNA low mRNA expression levels for DIAPH1 increased, and the mRNA expression level was statistically significant (p<0.05). Prognosis-wise, the effect of mRNA expression on survival in the absence of disease was meaningful for FLNA (p=0.011). Discussion and Conclusion: Bioinformatic analysis data in DIAPH1, WASP, MYH9, ACNT1, FLNA, and TUBB1 genes, which are important in CRC pathogenesis revealed in this study, will be a guide for future laboratory studies.


2021 ◽  
Vol 10 ◽  
Author(s):  
Jingbo Qi ◽  
Zhiqiu Hu ◽  
Shaoqun Liu ◽  
Fan Li ◽  
Sheng Wang ◽  
...  

Colorectal cancer (CRC) is the third most common cancer worldwide. Here, we identified tumor-associated macrophages (TAMs) as regulators of genes in CRC. In total, the expressions of 457 genes were dysregulated after TAM coculture; specifically, 344 genes were up-regulated, and 113 genes were down-regulated. Bioinformatic analysis implied that these TAM-related genes were associated with regulation of the processes of macromolecule metabolism, apoptosis, cell death, programmed cell death, and the response to stress. To further uncover the interplay among these proteins, we constructed a PPI network; 15 key regulators were identified in CRC, including VEGFA, FN1, JUN, CDH1, MAPK8, and FOS. Among the identified genes, we focused on PSMA2 and conducted loss-of-function experiments to validate the functions of PSMA2 in CRC. To further determine the mechanism by which PSMA2 affected CRC, we conducted multiple assays in CRC cell lines and tissues. PSMA2 enhanced the proliferation, migration and invasion of CRC cells. Moreover, our data indicated that PSMA2 expression was dramatically increased in stage 1, stage 2, stage 3, and stage 4 CRC samples. Our data indicated that PSMA2 was one target of miR-132. A miR-132 mimic greatly hindered CRC cell proliferation. In addition, the luciferase assay results revealed that miR-132 directly regulated PSMA2. Moreover, our data indicated that miR-132 expression was greatly decreased in CRC samples, which was associated with longer survival times of CRC patients, implying that miR-132 was a probable biomarker for CRC. Collectively, these data indicate that PSMA2 is a promising target for the therapy of CRC.


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