Integrated Analysis of miRNA and mRNA Endorses a Twenty miRNAs Signature for Colorectal Carcinoma

Angius, Andrea; Uva, Paolo; Pira, Giovanna; Muroni, Maria Rosaria; Sotgiu, Giovanni; Saderi, Laura; Uleri, Elena; Caocci, Maurizio; Ibba, Gabriele; Cesaraccio, Maria Rosaria; Serra, Caterina; Carru, Ciriaco; Manca, Alessandra; Sanges, Francesca; Porcu, Alberto; Dolei, A; Scanu, Antonio Mario; Rocca, Paolo; Miglio, Maria Rosaria De

doi:10.3390/ijms20164067

Cited by 34 publications

(27 citation statements)

References 59 publications

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“…Therefore, in order to improve the sensitivity of clinical diagnosis of tumor biomarkers, we can screen combined biomarkers of CRC. Andrea Angius et al found an integrated signature of 20 deregulated miRNAs that could be evaluated as potential prognostic biomarkers [12], Chuanpeng Dong et al identified that an eight-gene signature in cancer stem cell signaling was associated with the overall survival patients with CRC [13]. Furthermore, the researcher identified a 6-gene signature predicting prognosis for CRC [14].…”

Section: Ivyspring International Publishermentioning

confidence: 99%

A Combined four-mRNA Signature Associated with Lymphatic Metastasis for Prognosis of Colorectal Cancer

Qiang

Zhao

et al. 2020

J. Cancer

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Background: Colorectal cancer (CRC) is one of the most common malignant tumors in the world. Lymph node metastasis (LNM) is a common mode of metastasis of CRC. However, the combined mRNA biomarkers associated with LNM of CRC that can effectively predict CRC prognosis have not been reported yet. Methods: To identify biomarkers that are associated with LNM, we collected data from the The Cancer Genome Atlas (TCGA) database. The edgeR package was searched to seek LNM-related genes by comparisons between cancer samples and normal colorectal tissues and between LNM and non-LNM (NLNM) of CRC. Univariate and multivariate regression analysis of genes in the intersection to build gene signature associated with independent prognosis of CRC, and then verified by Kaplan-Meier curve and log-rank test, receiver operating characteristic (ROC) curve was used to determine the efficiency of survival prediction of our four-mRNA signature. Finally, the potential molecular mechanisms and properties of these gene signature were also explored with functional and pathway enrichment analysis. Results: 329 mRNAs were up-regulated in CRC tissues with LNM, and 8461 mRNAs were up-regulated in CRC tissues, the intersection is 100 mRNAs. After univariate and multivariate Cox regression analysis of 100 mRNAs, a novel four LNM related mRNAs (EPHA8, KRT85, GABRA3, and CLPSL1) were screened as independent prognostic indicators of CRC. Surprisingly, the four-mRNA signature can predict the prognosis of CRC patients independently of clinical factors andthe area under the curve (AUC) of the ROC is 0.730. The novel four-mRNA signature was used to identify high and low-risk groups. Stratified analysis indicated the risk score based on four-mRNA signature was an independent prognostic indicator for female, T3+T4, N1+N2 ,stage III+IV and patients with no new tumor event. Functional annotation of this risk model in high-risk patients revealed that pathways associated with neuroactive ligand-receptor interaction, estrogen signaling pathway, and steroid hormone biosynthesis. Conclusions: By conducting TCGA data mining, our study demonstrated that a four-mRNA signature associated with LNM can be used as a combined biomarker for independent prognosis of CRC.

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Section: Ivyspring International Publishermentioning

confidence: 99%

A Combined four-mRNA Signature Associated with Lymphatic Metastasis for Prognosis of Colorectal Cancer

Qiang

Zhao

et al. 2020

J. Cancer

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“…As such, miRNAs interact with extensive intracellular signaling networks and have effect on many processes involved in cancer such as metabolic homeostasis, proliferation, and apoptosis [6]. Aberrant expression of miRNAs can contribute to carcinogenesis by excessive suppression of anti-tumor genes or a lack of suppression of oncogenes [7,9]. Furthermore, miRNAs target genes within key pathways involved in drug resistance and thus sensitivity to chemotherapeutics [6].…”

Section: Introductionmentioning

confidence: 99%

Proteomic Analysis of miR-195 and miR-497 Replacement Reveals Potential Candidates that Increase Sensitivity to Oxaliplatin in MSI/P53wt Colorectal Cancer Cells

Poel

Boyd

Beekhof

et al. 2019

Cells

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Most patients with advanced colorectal cancer (CRC) eventually develop resistance to systemic combination therapy. miR-195-5p and miR-497-5p are downregulated in CRC tissues and associated with drug resistance. Sensitization to 5-FU, oxaliplatin, and irinotecan by transfection with miR-195-5p and miR-497-5p mimics was studied using cell viability and clonogenic assays in cell lines HCT116, RKO, DLD-1, and SW480. In addition, proteomic analysis of transfected cells was implemented to identify potential targets. Significantly altered proteins were subjected to STRING (protein-protein interaction networks) database analysis to study the potential mechanisms of drug resistance. Cell viability analysis of transfected cells revealed increased sensitivity to oxaliplatin in microsatellite instable (MSI)/P53 wild-type HCT116 and RKO cells. HCT116 transfected cells formed significantly fewer colonies when treated with oxaliplatin. In sensitized cells, proteomic analysis showed 158 and 202 proteins with significantly altered expression after transfection with miR-195-5p and miR-497-5p mimics respectively, of which CHUK and LUZP1 proved to be coinciding downregulated proteins. Resistance mechanisms of these proteins may be associated with nuclear factor kappa-B signaling and G1 cell-cycle arrest. In conclusion, miR-195-5p and miR-497-5p replacement enhanced sensitivity to oxaliplatin in treatment naïve MSI/P53 wild-type CRC cells. Proteomic analysis revealed potential miRNA targets associated with the cell-cycle which possibly bare a relation with chemotherapy sensitivity.

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“…Furthermore, a study identified a potential role for miR-224 in CRC progression ( 41 ). Finally, high expression levels miR-224 have been associated with worse survival of patients in CRC ( 42 ).…”

Section: Discussionmentioning

confidence: 99%

MicroRNAs Expression Patterns Predict Tumor Mutational Burden in Colorectal Cancer

et al. 2021

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BackgroundTumor mutational burden (TMB) could be a measure of response to immune checkpoint inhibitors therapy for patients with colorectal cancer (CRC). MicroRNAs (miRNAs) participate in anticancer immune responses. In the present study, we determined miRNA expression patterns in patients with CRC and built a signature that predicts TMB.MethodsNext generation sequencing (NGS) on formalin-fixed paraffin-embedded samples from CRC patients was performed to measure TMB levels. We used datasets from The Cancer Genome Atlas to compare miRNA expression patterns in samples with high and low TMB from patients with CRC. We created an miRNA-based signature index using the selection operator (LASSO) and least absolute shrinkage method from the training set. We used an independent test set as internal validation. We used real-time polymerase chain reaction (RT-PCR) to validate the miRNA-based signature classifier.ResultsTwenty-seven samples from CRC patients underwent NGS to determine the TMB level. We identified four miRNA candidates in the training set for predicting TMB (N = 311). We used the test set (N = 204) for internal validation. The four-miRNA-based signature classifier was an accurate predictor of TMB, with accuracy 0.963 in the training set. In the test set, it was 0.902; and it was 0.946 in the total set. The classifier was superior to microsatellite instability (MSI) for predicting TMB in TCGA dataset. In the validation cohort, MSI status more positively correlated with TMB levels than did the classifier. Validation from RT-qPCR showed good target discrimination of the classifier for TMB prediction.ConclusionTo our knowledge, this is the first miRNA-based signature classifier validated using high quality clinical data to accurately predict TMB level in patients with CRC.

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Integrated Analysis of miRNA and mRNA Endorses a Twenty miRNAs Signature for Colorectal Carcinoma

Cited by 34 publications

References 59 publications

A Combined four-mRNA Signature Associated with Lymphatic Metastasis for Prognosis of Colorectal Cancer

A Combined four-mRNA Signature Associated with Lymphatic Metastasis for Prognosis of Colorectal Cancer

Proteomic Analysis of miR-195 and miR-497 Replacement Reveals Potential Candidates that Increase Sensitivity to Oxaliplatin in MSI/P53wt Colorectal Cancer Cells

MicroRNAs Expression Patterns Predict Tumor Mutational Burden in Colorectal Cancer

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