Small RNA Sequencing Identifies a Six-MicroRNA Signature
Enabling Classification of Brain Metastases According to their
Origin

J 2023

Small RNA Sequencing Identifies a Six-MicroRNA Signature Enabling Classification of Brain Metastases According to their Origin

ROŠKOVÁ, Ivana; Marek VEČEŘA; Lenka RADOVÁ; Karolína TRACHTOVÁ; František SIEGL et al.

Základní údaje

Originální název

Small RNA Sequencing Identifies a Six-MicroRNA Signature Enabling Classification of Brain Metastases According to their Origin

Autoři

Vydání

CANCER GENOMICS & PROTEOMICS, ATHENS, INT INST ANTICANCER RESEARCH, 2023, 1109-6535

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: 2.600

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14740/23:00131080

Organizační jednotka

Středoevropský technologický institut

Klíčová slova anglicky

Brain metastases; microRNA; small RNA sequencing; classifier; diagnosis

Štítky

14110112, 14110131, 14110224, 14110513, 14110811, 14110812, CF BIOIT, CF GEN, NÚVR_CEITEC, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 15. 10. 2024 15:09, Ing. Martina Blahová

Anotace

V originále

Background/Aim: Brain metastases (BMs) are the most frequent intracranial tumors in adults and one of the greatest challenges for modern oncology. Most are derived from lung, breast, renal cell, and colorectal carcinomas and melanomas. Up to 14% of patients are diagnosed with BMs of unknown primary, which are commonly characterized by an early and aggressive metastatic spread. It is important to discover novel biomarkers for early identification of BM origin, allowing better management of patients with this disease. Our study focused on microRNAs (miRNAs), which are very stable in frozen native and FFPE tissues and have been shown to be sensitive and specific diagnostic biomarkers of cancer. We aimed to identify miRNAs with significantly different expression in the five most frequent groups of BMs and develop a diagnostic classifier capable of sensitive and specific classification of BMs. Materials and Methods: Total RNA enriched for miRNAs was isolated using the mirVana miRNA Isolation Kit from 71 fresh-frozen histopathologically confirmed BM tissues originating in 5 cancer types. Sequencing libraries were prepared using the QIAseq miRNA Library Kit and sequenced on the NextSeq 500 platform. MiRNA expression was further validated by RT-qPCR. Results: Differential analysis identified 373 miRNAs with significantly different expression between 5 BM groups (p<0.001). A classifier model was developed based on the expression of 6 miRNAs (hsa-miR-141-3p, hsa-miR-141-5p, hsa-miR-146a-5p, hsa-miR-194-5p, hsa-miR-200b-3p and hsa-miR-365b-5p) with the ability to correctly classify 91.5% of samples. Subsequent validation confirmed both significantly different expression of selected miRNAs in 5 BM groups as well as their diagnostic potential. Conclusion: To date, our study is the first to analyze miRNA expression in various types of BMs using small RNA sequencing to develop a diagnostic classifier and, thus, to help stratify BMs of unknown primary. The presented results confirm the importance of studying the dysregulated expression of miRNAs in BMs and the diagnostic potential of the validated 6-miRNA signature.

Návaznosti

LX22NPO5102, projekt VaV

Název: Národní ústav pro výzkum rakoviny (Akronym: NÚVR)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Národní ústav pro výzkum rakoviny, 5.1 EXCELES

LX22NPO5107, projekt VaV

Název: Národní ústav pro neurologický výzkum

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Národní ústav pro neurologický výzkum, 5.1 EXCELES

NV18-03-00398, projekt VaV

Název: Rozšíření současných prognostických skórovacích systémů u mozkových metastáz o mikroRNA profilování s cílem individualizace pooperační péče

Investor: Ministerstvo zdravotnictví ČR, Rozšíření současných prognostických skórovacích systémů u mozkových metastáz o mikroRNA profilování s cílem individualizace pooperační péče

90132, velká výzkumná infrastruktura

Název: NCMG II

Přiložené soubory

Small_RNA_Sequencing_Identifies_a_Six-MicroRNA_Signature_Enabling_Classification_of_Brain_Metastases_According_to_their_Origin.pdf

Citovat

ROŠKOVÁ, Ivana; Marek VEČEŘA; Lenka RADOVÁ; Karolína TRACHTOVÁ; František SIEGL; Markéta HERMANOVÁ; Michal HENDRYCH; Leoš KŘEN; Václav VYBÍHAL; Hana VALEKOVÁ; Petra KASPAROVA; Ivana KOLOUŠKOVÁ; Tomáš KAZDA; Ondřej SLABÝ; Radim JANČÁLEK; Jiří ŠÁNA a Martin SMRČKA. Small RNA Sequencing Identifies a Six-MicroRNA Signature Enabling Classification of Brain Metastases According to their Origin. CANCER GENOMICS & PROTEOMICS. ATHENS: INT INST ANTICANCER RESEARCH, 2023, roč. 20, č. 1, s. 18-29. ISSN 1109-6535. Dostupné z: https://doi.org/10.21873/cgp.20361.

@article{2293483,
   author = {Rošková, Ivana and Večeřa, Marek and Radová, Lenka and Trachtová, Karolína and Siegl, František and Hermanová, Markéta and Hendrych, Michal and Křen, Leoš and Vybíhal, Václav and Valeková, Hana and Kasparova, Petra and Koloušková, Ivana and Kazda, Tomáš and Slabý, Ondřej and Jančálek, Radim and Šána, Jiří and Smrčka, Martin},
   article_location = {ATHENS},
   article_number = {1},
   doi = {https://doi.org/10.21873/cgp.20361},
   keywords = {Brain metastases; microRNA; small RNA sequencing; classifier; diagnosis},
   language = {eng},
   issn = {1109-6535},
   journal = {CANCER GENOMICS & PROTEOMICS},
   title = {Small RNA Sequencing Identifies a Six-MicroRNA Signature Enabling Classification of Brain Metastases According to their Origin},
   url = {https://cgp.iiarjournals.org/content/20/1/18},
   volume = {20},
   year = {2023}
}

TY  - JOUR
ID  - 2293483
AU  - Rošková, Ivana - Večeřa, Marek - Radová, Lenka - Trachtová, Karolína - Siegl, František - Hermanová, Markéta - Hendrych, Michal - Křen, Leoš - Vybíhal, Václav - Valeková, Hana - Kasparova, Petra - Koloušková, Ivana - Kazda, Tomáš - Slabý, Ondřej - Jančálek, Radim - Šána, Jiří - Smrčka, Martin
PY  - 2023
TI  - Small RNA Sequencing Identifies a Six-MicroRNA Signature Enabling Classification of Brain Metastases According to their Origin
JF  - CANCER GENOMICS & PROTEOMICS
VL  - 20
IS  - 1
SP  - 18-29
EP  - 18-29
PB  - INT INST ANTICANCER RESEARCH
SN  - 11096535
KW  - Brain metastases
KW  - microRNA
KW  - small RNA sequencing
KW  - classifier
KW  - diagnosis
UR  - https://cgp.iiarjournals.org/content/20/1/18
N2  - Background/Aim: Brain metastases (BMs) are the most frequent intracranial tumors in adults and one of the greatest challenges for modern oncology. Most are derived from lung, breast, renal cell, and colorectal carcinomas and melanomas. Up to 14% of patients are diagnosed with BMs of unknown primary, which are commonly characterized by an early and aggressive metastatic spread. It is important to discover novel biomarkers for early identification of BM origin, allowing better management of patients with this disease. Our study focused on microRNAs (miRNAs), which are very stable in frozen native and FFPE tissues and have been shown to be sensitive and specific diagnostic biomarkers of cancer. We aimed to identify miRNAs with significantly different expression in the five most frequent groups of BMs and develop a diagnostic classifier capable of sensitive and specific classification of BMs. Materials and Methods: Total RNA enriched for miRNAs was isolated using the mirVana miRNA Isolation Kit from 71 fresh-frozen histopathologically confirmed BM tissues originating in 5 cancer types. Sequencing libraries were prepared using the QIAseq miRNA Library Kit and sequenced on the NextSeq 500 platform. MiRNA expression was further validated by RT-qPCR. Results: Differential analysis identified 373 miRNAs with significantly different expression between 5 BM groups (p<0.001). A classifier model was developed based on the expression of 6 miRNAs (hsa-miR-141-3p, hsa-miR-141-5p, hsa-miR-146a-5p, hsa-miR-194-5p, hsa-miR-200b-3p and hsa-miR-365b-5p) with the ability to correctly classify 91.5% of samples. Subsequent validation confirmed both significantly different expression of selected miRNAs in 5 BM groups as well as their diagnostic potential. Conclusion: To date, our study is the first to analyze miRNA expression in various types of BMs using small RNA sequencing to develop a diagnostic classifier and, thus, to help stratify BMs of unknown primary. The presented results confirm the importance of studying the dysregulated expression of miRNAs in BMs and the diagnostic potential of the validated 6-miRNA signature.
ER  -

ROŠKOVÁ, Ivana; Marek VEČEŘA; Lenka RADOVÁ; Karolína TRACHTOVÁ; František SIEGL; Markéta HERMANOVÁ; Michal HENDRYCH; Leoš KŘEN; Václav VYBÍHAL; Hana VALEKOVÁ; Petra KASPAROVA; Ivana KOLOUŠKOVÁ; Tomáš KAZDA; Ondřej SLABÝ; Radim JANČÁLEK; Jiří ŠÁNA a Martin SMRČKA. Small RNA Sequencing Identifies a Six-MicroRNA Signature Enabling Classification of Brain Metastases According to their Origin. \textit{CANCER GENOMICS \&{} PROTEOMICS}. ATHENS: INT INST ANTICANCER RESEARCH, 2023, roč.~20, č.~1, s.~18-29. ISSN~1109-6535. Dostupné z: https://doi.org/10.21873/cgp.20361.

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