Dynamic plasma microRNAs are biomarkers for prognosis and early detection of recurrence in colorectal cancer

Yuan, Zixu; Baker, Kelsey K.; Redman, Mary W.; Wang, Lei; Adams, Scott V.; Yu, Ming; Dickinson, Brandon; Makar, Karen W.; Ulrich, Neli; Böhm, Jürgen; Wurscher, Michelle A.; Westerhoff, Maria; Medwell, Steve; Moonka, Ravi; Sinanan, Mika; Fichera, Alessandro; Vickers, Kathy; Grady, William M.

doi:10.1038/bjc.2017.266

Cited by 46 publications

(33 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…They identified markers of inflammation in VAT, which supports prior evidence regarding the role of visceral adiposity and cancer (31). Ristau and Yuan and colleagues have also investigated miRNAs as prognostic biomarkers (33,49). We evaluated DNA methylation patterns, for example in relation to health behaviors (30,50) and contributed to a study that showed the potential of fecal microbiota for early-stage detection of colorectal cancer (34).…”

Section: Resultssupporting

confidence: 65%

The ColoCare Study: A Paradigm of Transdisciplinary Science in Colorectal Cancer Outcomes

Ulrich

Gigic

Böhm

et al. 2019

Cancer Epidemiology, Biomarkers &Amp; Prevention

Self Cite

View full text Add to dashboard Cite

Background: Colorectal cancer is a leading cause of cancer death. Biomarkers to predict treatment outcomes are needed, as is evidence whether postdiagnosis diet and lifestyle can affect well-being and clinical outcomes. The international ColoCare Consortium aims to identify new biologic markers (e.g., metabolomic, transcriptomic, metagenomic, genetic, epigenetic, proteomic markers) that predict clinical outcomes, and to characterize associations between modifiable risk factors (e.g., diet, supplement use, physical activity) with shortterm and long-term patient-reported and clinical outcomes among patients with colorectal cancer. Methods/Results: ColoCare is recruiting newly diagnosed patients with colorectal cancer across six sites in the United States and one site in Germany. As of April 2018, we have recruited >2,000 patients across all sites. Our projected enrollment is >4,000 multiethnic patients with colorectal cancer. The study includes uniformly collected, comprehensive sets of data and biospecimens at multiple time points up to 5 years after diagnosis. Treatment and clinical data are abstracted from medical records and centrally harmonized. Biospecimens are archived according to standardized procedures. Our initial studies demonstrated metabolic differences in adipose tissue types. We further reported on associations of biological factors (e.g., inflammation, DNA methylation, metabolomics) with lifestyle factors (e.g., adiposity, smoking, physical activity, dietary supplement use) or joint associations with clinical outcomes. Conclusions: ColoCare is a consortium for the investigation of multilevel factors relevant to colorectal cancer survivorship. Impact: The combination of a comprehensive set of biospecimens collected at multiple time points, jointly with detailed assessments of health behaviors and other prognostic factors, results in a unique resource that facilitates wide-ranging, innovative, and impactful research on colorectal cancer.

show abstract

Section: Resultssupporting

confidence: 65%

The ColoCare Study: A Paradigm of Transdisciplinary Science in Colorectal Cancer Outcomes

Ulrich

Gigic

Böhm

et al. 2019

Cancer Epidemiology, Biomarkers &Amp; Prevention

Self Cite

View full text Add to dashboard Cite

show abstract

“…In the third study, miR-29a showed promising prognostic significance and could discriminate patients with recurrence from those without recurrence with an AUC of 0.703 (95% CI 0.562, 0.845). Meanwhile, in this study, preoperative high plasma miR-29a levels were associated with increased recurrence risk (HR 2.61; 95% CI 1.34-5.07; P < 0.005) [40].…”

Section: Recurrence Prediction Value Of Mir-29 and The Combination Mamentioning

confidence: 45%

“…After manually screening the titles, abstracts and keywords and then checking the full texts, 9 articles involving 10 studies for individual miR-29 and 5 articles containing 6 studies for miRNA combination markers based on miR-29 that met the inclusion norm were finally selected for the diagnostic meta-analysis while six publications including eight studies evaluating the survival outcome were identified eligible in the prognostic meta-analysis [27][28][29][30][31][32][33][34][35][36][37][38][39]. Moreover, three studies assessed the roles of miR-29 and miRNA combination markers in the recurrence prediction of CRC and one study evaluated the biomarker role in the metastasis prediction in CRC [40][41][42][43]. The characteristics of the eligible studies were summarized in Tables 1, 2 and 3.…”

Section: Study Identification and Characteristics Of Included Studiesmentioning

confidence: 99%

Integrated analyses of microRNA-29 family and the related combination biomarkers demonstrate their widespread influence on risk, recurrence, metastasis and survival outcome in colorectal cancer

et al. 2019

View full text Add to dashboard Cite

Background Emerging evidence has revealed miR-29 family as promising biomarkers for colorectal cancer (CRC), but their biomarker potential and molecular mechanisms remain poorly understood. Methods We performed a comprehensive meta-analysis to evaluate the biomarker performance of individual miR-29 and the related miRNA combination biomarkers. Meanwhile, we conducted an integrative bioinformatics analysis to unfold the underlying biological function of miR-29 and their relationship with CRC. Results Using miR-29 expression to diagnose CRC produced 0.82 area under the curve, 70% sensitivity and 81% specificity while the combination biomarkers based on miR-29 enhanced the diagnostic power with an AUC of 0.86, a sensitivity of 78% and a specificity of 91%. For the prognosis evaluation, patients with higher expression of miR-29 had better survival outcome (pooled HR 0.78; 95% CI 0.56–1.07). In addition, miR-29 has also been identified as potential biomarker for predicting recurrence and metastasis in CRC. Then the genes regulated by the miR-29 family were retrieved and found closely associated with the molecular pathogenesis of CRC according to the gene ontology and pathway analysis. Furthermore, hub nodes and significant modules were identified from the protein–protein interaction network constructed with miR-29 family targets, which were also confirmed highly involved in the establishment and development of CRC. Conclusions Current evidences suggest miR-29 family may become promising biomarkers for risk, recurrence, metastasis and survival outcome of CRC. Meanwhile our data highlight the potential clinical use of miRNA combination biomarkers. Nevertheless, further prospective studies are warranted before the application of the useful biomarkers in the clinical.

show abstract

“…For instance, we observed significant interactions between miR-29a/b/c and collagens (COL1A1, COL2A1, COL4A1/2, COL5A1/2/3), laminins (LAMA2, LAMC2) and integrins (ITGA6, ITGB1). Recent studies have shown a critical involvement of miR-29, which was demonstrated as a prognostic marker in colon cancer, in the regulation of ECM related gene expression homeostasis [48,49]. On the other hand, tumor cells cultivated in a 3D environment exhibit differential expression of integrins due to diminished cell contact with the surface [50,51].…”

Section: Discussionmentioning

confidence: 99%

3D Cell Culture-Based Global miRNA Expression Analysis Reveals miR-142-5p as a Theranostic Biomarker of Rectal Cancer Following Neoadjuvant Long-Course Treatment

et al. 2020

View full text Add to dashboard Cite

Altered expression of miRNAs in tumor tissue encourages the translation of this specific molecular pattern into clinical practice. However, the establishment of a selective biomarker signature for many tumor types remains an inextricable challenge. For this purpose, a preclinical experimental design, which could maintain a fast and sensitive discovery of potential biomarkers, is in demand. The present study suggests that the approach of 3D cell cultures as a preclinical cancer model that is characterized to mimic a natural tumor environment maintained in solid tumors could successfully be employed for the biomarker discovery and validation. Subsequently, in this study, we investigated an environment-dependent miRNA expression changes in colorectal adenocarcinoma DLD1 and HT29 cell lines using next-generation sequencing (NGS) technology. We detected a subset of 16 miRNAs differentially expressed in both cell lines cultivated in multicellular spheroids compared to expression levels in cells grown in 2D. Furthermore, results of in silico miRNA target analysis showed that miRNAs, which were differentially expressed in both cell lines grown in MCS, are involved in the regulation of molecular mechanisms implicated in cell adhesion, cell-ECM interaction, and gap junction pathways. In addition, integrins and platelet-derived growth factor receptors were determined to be the most significant target genes of deregulated miRNAs, which was concordant with the environment-dependent gene expression changes validated by RT-qPCR. Our results revealed that 3D microenvironment-dependent deregulation of miRNA expression in CRC cells potentially triggers essential molecular mechanisms predominantly including the regulation of cell adhesion, cell–cell, and cell–ECM interactions important in CRC initiation and development. Finally, we demonstrated increased levels of selected miR-142-5p in rectum tumor tissue samples after neoadjuvant long course treatment compared to miR-142-5p expression levels in tumor biopsy samples collected before the therapy. Remarkably, the elevation of miR-142-5p expression remained in tumor samples compared to adjacent normal rectum tissue as well. Therefore, the current study provides valuable insights into the molecular miRNA machinery of CRC and proposes a potential miRNA signature for the assessment of CRC in further clinical research.

show abstract

Dynamic plasma microRNAs are biomarkers for prognosis and early detection of recurrence in colorectal cancer

Cited by 46 publications

References 38 publications

The ColoCare Study: A Paradigm of Transdisciplinary Science in Colorectal Cancer Outcomes

The ColoCare Study: A Paradigm of Transdisciplinary Science in Colorectal Cancer Outcomes

Integrated analyses of microRNA-29 family and the related combination biomarkers demonstrate their widespread influence on risk, recurrence, metastasis and survival outcome in colorectal cancer

3D Cell Culture-Based Global miRNA Expression Analysis Reveals miR-142-5p as a Theranostic Biomarker of Rectal Cancer Following Neoadjuvant Long-Course Treatment

Contact Info

Product

Resources

About