A specific microRNA profile as predictive biomarker for systemic treatment in patients with metastatic colorectal cancer

Autor: Nicole C.T. van Grieken, Wim Trypsteen, Henk L. Dekker, Lotte Bakkerus, Hans van Vliet, Elske C. Gootjes, Cornelis Verhoef, Henk M.W. Verheul, Tineke E. Buffart, Dennis Poel
Přispěvatelé: Surgery, Medical oncology, VU University medical center, Medical oncology laboratory, CCA - Imaging and biomarkers, Pathology, AGEM - Re-generation and cancer of the digestive system, Internal medicine
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Oncology
Male
Cancer Research
Colorectal cancer
medicine.medical_treatment
Biopsy
chemotherapy
Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14]
0302 clinical medicine
Neoplasm Metastasis
Original Research
Disease Management
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Prognosis
Immunohistochemistry
Treatment Outcome
030220 oncology & carcinogenesis
Cohort
Biomarker (medicine)
Female
Colorectal Neoplasms
medicine.drug
Diagnostic Imaging
medicine.medical_specialty
Bevacizumab
Clinical Decision-Making
colorectal cancer
lcsh:RC254-282
Capecitabine
03 medical and health sciences
SDG 3 - Good Health and Well-being
Internal medicine
medicine
Humans
Radiology
Nuclear Medicine and imaging
metastases
miRNA
Neoplasm Staging
Chemotherapy
business.industry
Gene Expression Profiling
Clinical Cancer Research
Computational Biology
medicine.disease
Oxaliplatin
MicroRNAs
030104 developmental biology
ROC Curve
response prediction
Neoplasm Grading
business
Transcriptome
serum
Progressive disease
Biomarkers
Zdroj: Cancer Medicine
Cancer Medicine, 9, 20, pp. 7558-7571
Poel, D, Gootjes, E C, Bakkerus, L, Trypsteen, W, Dekker, H, van der Vliet, H J, van Grieken, N C T, Verhoef, C, Buffart, T E & Verheul, H M W 2020, ' A specific microRNA profile as predictive biomarker for systemic treatment in patients with metastatic colorectal cancer ', Cancer Medicine, vol. 9, no. 20, pp. 7558-7571 . https://doi.org/10.1002/cam4.3371
Cancer Medicine, Vol 9, Iss 20, Pp 7558-7571 (2020)
Cancer Medicine, 9, 7558-7571
Cancer Medicine, 9(20), 7558-7571. John Wiley & Sons Ltd.
Cancer Medicine, 9(20), 7558-7571. John Wiley and Sons Ltd
ISSN: 2045-7634
DOI: 10.1002/cam4.3371
Popis: Background Palliative systemic therapy is currently standard of care for patients with extensive metastatic colorectal cancer (mCRC). A biomarker predicting chemotherapy benefit which prevents toxicity from ineffective treatment is urgently needed. Therefore, a previously developed tissue‐derived microRNA profile to predict clinical benefit from chemotherapy was evaluated in tissue biopsies and serum from patients with mCRC. Methods Samples were prospectively collected from patients (N = 132) who were treated with capecitabine or 5‐FU/LV with oxaliplatin ± bevacizumab. Response evaluation was performed according to RECIST 1.1 after three or four cycles, respectively. Baseline tissue and serum miRNAs expression levels of miR‐17‐5p, miR‐20a‐5p, miR‐30a‐5p, miR‐92a‐3p, miR‐92b‐3p, and miR‐98‐5p were quantified with RT‐qPCR and droplet digital PCR, respectively. Combined predictive performance of selected variables was tested using logistic regression analysis. Results From 132 patients, 81 fresh frozen tissue biopsies from metastases and 93 serum samples were available. Based on expression levels of miRNAs in tissue, progressive disease could be predicted with an AUC of 0.85 (95% CI:0.72‐0.91) and response could be predicted with an AUC of 0.70 (95% CI:0.56‐0.80). This did not outperform clinical parameters alone (respectively P = .14 and P = .27). Expression levels of miR‐92a‐3p and miR‐98‐5p in serum significantly improved the predictive value of clinical parameters for response to chemotherapy (AUC 0.74, 95% CI:0.64‐0.84, P = .003) in this cohort. Conclusions The additive predictive value to clinical parameters of the tissue‐derived six miRNA profile for clinical benefit could not be validated in patients with mCRC treated with first‐line systemic therapy. Although miR‐92a‐3p and miR‐98‐5p serum levels improved the predictive value of clinical parameters, it remained insufficient for clinical decision‐making.
For miR‐17‐5p, miR‐20a‐5p, miR‐30a‐5p, miR‐92a‐3p, miR‐92b‐3p and miR‐98‐5p no correlation was observed between tissue and serum miRNA expression levels in patients with metastatic colorectal cancer (mCRC). The predictive value of this tissue‐derived 6 miRNA profile for clinical benefit from systemic treatment could not be validated in patients with mCRC starting first line systemic therapy.
Databáze: OpenAIRE
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