Candidate MicroRNA Biomarkers of Therapeutic Response to
Sunitinib in Metastatic Renal Cell Carcinoma: A Validation
Study in Patients with Extremely Good and Poor Response

J 2018

Candidate MicroRNA Biomarkers of Therapeutic Response to Sunitinib in Metastatic Renal Cell Carcinoma: A Validation Study in Patients with Extremely Good and Poor Response

KOVÁČOVÁ, Júlia; Jaroslav JURÁČEK; Alexandr POPRACH; T. BUCHLER; J. KOPECKY et al.

Základní údaje

Originální název

Candidate MicroRNA Biomarkers of Therapeutic Response to Sunitinib in Metastatic Renal Cell Carcinoma: A Validation Study in Patients with Extremely Good and Poor Response

Autoři

KOVÁČOVÁ, Júlia; Jaroslav JURÁČEK; Alexandr POPRACH; T. BUCHLER; J. KOPECKY; O. FIALA; Marek SVOBODA a Ondřej SLABÝ

Vydání

Anticancer Research, Athens, International Institute of Anticancer Research, 2018, 0250-7005

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30204 Oncology

Stát vydavatele

Řecko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 1.935

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14740/18:00106955

Organizační jednotka

Středoevropský technologický institut

Klíčová slova anglicky

Renal cell carcinoma; microRNA; sunitinib; therapy response; prediction

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 13. 3. 2019 13:00, Mgr. Pavla Foltynová, Ph.D.

Anotace

V originále

Background/Aim: Targeted therapy with the tyrosine kinase inhibitor sunitinib is used in the first line of metastatic renal cell carcinoma (mRCC) treatment. The aim of the present study was independent validation of microRNAs (miRNAs) identified in previous studies as biomarkers predicting response to sunitinib therapy. Materials and Methods: Based on a literature search, 10 miRNAs were chosen from six relevant studies as candidates for validation: miR-155, miR-484, miR-221, miR-222 , miR-425 , miR-133, miR-410, miR-141, miR-628 and miR-942. Validation of these miRNAs was performed on cohort of 56 patients with mRCC with extremely good or poor response responses to sunitinib treatment using quantitative reverse transcription-polymerase chain reaction. Patients were divided into either responding (n=24) or non-responding (n=32) groups to sunitinib treatment according to Response Evaluation Criteria in Solid Tumors and progression free survival (PFS). All patients in the responding group had PFS longer than 18 months, PFS of non-responders was shorter than 6 months in all cases. Results: miR-942 and miR-133 were confirmed as being differentially expressed in tumors of responding and non-responding patients. It was not possible to validate the predictive value of other tested miRNAs, however, expression of miR-221 and miR-425 tended to be positively associated with therapeutic response (p<0.1). We further developed a model based on the combination of miR-942 and miR-133 expression, that enabled identification of non-responding patients with mRCC with sensitivity of 78% and specificity of 79% (area under the curve=0.8071). Conclusion: Following further independent validation, detection of these miRNAs may prevent unnecessary and costly approaches to therapy in non-responding patients with mRCC.

Návaznosti

NV15-34678A, projekt VaV

Název: Molekulární prognostické a prediktivní faktory u pacientů s metastatickým renálním karcinomem léčených tyrozinkinázovými inhibitory

Citovat

KOVÁČOVÁ, Júlia; Jaroslav JURÁČEK; Alexandr POPRACH; T. BUCHLER; J. KOPECKY; O. FIALA; Marek SVOBODA a Ondřej SLABÝ. Candidate MicroRNA Biomarkers of Therapeutic Response to Sunitinib in Metastatic Renal Cell Carcinoma: A Validation Study in Patients with Extremely Good and Poor Response. Anticancer Research. Athens: International Institute of Anticancer Research, 2018, roč. 38, č. 5, s. 2961-2965. ISSN 0250-7005. Dostupné z: https://doi.org/10.21873/anticanres.12546.

@article{1477738,
   author = {Kováčová, Júlia and Juráček, Jaroslav and Poprach, Alexandr and Buchler, T. and Kopecky, J. and Fiala, O. and Svoboda, Marek and Slabý, Ondřej},
   article_location = {Athens},
   article_number = {5},
   doi = {https://doi.org/10.21873/anticanres.12546},
   keywords = {Renal cell carcinoma; microRNA; sunitinib; therapy response; prediction},
   language = {eng},
   issn = {0250-7005},
   journal = {Anticancer Research},
   title = {Candidate MicroRNA Biomarkers of Therapeutic Response to Sunitinib in Metastatic Renal Cell Carcinoma: A Validation Study in Patients with Extremely Good and Poor Response},
   url = {http://ar.iiarjournals.org/content/38/5/2961.abstract},
   volume = {38},
   year = {2018}
}

TY  - JOUR
ID  - 1477738
AU  - Kováčová, Júlia - Juráček, Jaroslav - Poprach, Alexandr - Buchler, T. - Kopecky, J. - Fiala, O. - Svoboda, Marek - Slabý, Ondřej
PY  - 2018
TI  - Candidate MicroRNA Biomarkers of Therapeutic Response to Sunitinib in Metastatic Renal Cell Carcinoma: A Validation Study in Patients with Extremely Good and Poor Response
JF  - Anticancer Research
VL  - 38
IS  - 5
SP  - 2961-2965
EP  - 2961-2965
PB  - International Institute of Anticancer Research
SN  - 02507005
KW  - Renal cell carcinoma
KW  - microRNA
KW  - sunitinib
KW  - therapy response
KW  - prediction
UR  - http://ar.iiarjournals.org/content/38/5/2961.abstract
N2  - Background/Aim: Targeted therapy with the tyrosine kinase inhibitor sunitinib is used in the first line of metastatic renal cell carcinoma (mRCC) treatment. The aim of the present study was independent validation of microRNAs (miRNAs) identified in previous studies as biomarkers predicting response to sunitinib therapy. Materials and Methods: Based on a literature search, 10 miRNAs were chosen from six relevant studies as candidates for validation: miR-155, miR-484, miR-221, miR-222 , miR-425 , miR-133, miR-410, miR-141, miR-628 and miR-942. Validation of these miRNAs was performed on cohort of 56 patients with mRCC with extremely good or poor response responses to sunitinib treatment using quantitative reverse transcription-polymerase chain reaction. Patients were divided into either responding (n=24) or non-responding (n=32) groups to sunitinib treatment according to Response Evaluation Criteria in Solid Tumors and progression free survival (PFS). All patients in the responding group had PFS longer than 18 months, PFS of non-responders was shorter than 6 months in all cases. Results: miR-942 and miR-133 were confirmed as being differentially expressed in tumors of responding and non-responding patients. It was not possible to validate the predictive value of other tested miRNAs, however, expression of miR-221 and miR-425 tended to be positively associated with therapeutic response (p<0.1). We further developed a model based on the combination of miR-942 and miR-133 expression, that enabled identification of non-responding patients with mRCC with sensitivity of 78% and specificity of 79% (area under the curve=0.8071). Conclusion: Following further independent validation, detection of these miRNAs may prevent unnecessary and costly approaches to therapy in non-responding patients with mRCC.
ER  -

KOVÁČOVÁ, Júlia; Jaroslav JURÁČEK; Alexandr POPRACH; T. BUCHLER; J. KOPECKY; O. FIALA; Marek SVOBODA a Ondřej SLABÝ. Candidate MicroRNA Biomarkers of Therapeutic Response to Sunitinib in Metastatic Renal Cell Carcinoma: A Validation Study in Patients with Extremely Good and Poor Response. \textit{Anticancer Research}. Athens: International Institute of Anticancer Research, 2018, roč.~38, č.~5, s.~2961-2965. ISSN~0250-7005. Dostupné z: https://doi.org/10.21873/anticanres.12546.

Přehled o publikaci