Nejvíce citovaný článek - PubMed ID 34993725
Small non-coding RNA profiling in breast cancer: plasma U6 snRNA, miR-451a and miR-548b-5p as novel diagnostic and prognostic biomarkers
INTRODUCTION: Breast cancer comprises the leading cause of cancer-related death in women. MicroRNAs (miRNAs) have emerged as important factors with concern to carcinogenesis and have potential for use as biomarkers. METHODS: This study provides a comprehensive evaluation of the microRNA expression in invasive breast carcinoma of no special type tissues compared with benign tissues via large-scale screening and the candidate-specific validation of 15 miRNAs and U6 snRNA applying qPCR and the examination of clinicopathological data. RESULTS: Of the six downregulated miRNAs, let-7c was identified as the most promising miRNA biomarker and its lower expression was linked with Ki-67 positivity, luminal B versus luminal A samples, multifocality, lymph node metastasis, and inferior PFS. Of the 9 upregulated sncRNAs, the data on U6 snRNA, miR-493 and miR-454 highlighted their potential oncogenic functions. An elevated U6 snRNA expression was associated with the tumor grade, Ki-67 positivity, luminal B versus A samples, lymph node metastasis, and worsened PFS (and OS) outcomes. An elevated miR-454 expression was detected in higher grades, Ki-67 positive and luminal B versus A samples. Higher miR-493 levels were noted for the tumor stage (and grade) and worse patient outcomes (PFS, OS). The data also suggested that miR-451a and miR-328 may have tumor suppressor roles, and miR-182 and miR-200c pro-oncogenic functions, while the remaining sncRNAs did not evince any significant associations. CONCLUSION: We showed particular microRNAs and U6 snRNA as differentially expressed between tumors and benign tissues and associated with clinicopathological parameters, thus potentially corresponding with important roles in breast carcinogenesis. Their importance should be further investigated and evaluated in follow-up studies to reveal their potential in clinical practice. INTRODUCTION: Breast cancer comprises the leading cause of cancer-related death in women. MicroRNAs (miRNAs) have emerged as important factors with concern to carcinogenesis and have potential for use as biomarkers. METHODS: This study provides a comprehensive evaluation of the microRNA expression in invasive breast carcinoma of no special type tissues compared with benign tissues via large-scale screening and the candidate-specific validation of 15 miRNAs and U6 snRNA applying qPCR and the examination of clinicopathological data. RESULTS: Of the six downregulated miRNAs, let-7c was identified as the most promising miRNA biomarker and its lower expression was linked with Ki-67 positivity, luminal B versus luminal A samples, multifocality, lymph node metastasis, and inferior PFS. Of the 9 upregulated sncRNAs, the data on U6 snRNA, miR-493 and miR-454 highlighted their potential oncogenic functions. An elevated U6 snRNA expression was associated with the tumor grade, Ki-67 positivity, luminal B versus A samples, lymph node metastasis, and worsened PFS (and OS) outcomes. An elevated miR-454 expression was detected in higher grades, Ki-67 positive and luminal B versus A samples. Higher miR-493 levels were noted for the tumor stage (and grade) and worse patient outcomes (PFS, OS). The data also suggested that miR-451a and miR-328 may have tumor suppressor roles, and miR-182 and miR-200c pro-oncogenic functions, while the remaining sncRNAs did not evince any significant associations. CONCLUSION: We showed particular microRNAs and U6 snRNA as differentially expressed between tumors and benign tissues and associated with clinicopathological parameters, thus potentially corresponding with important roles in breast carcinogenesis. Their importance should be further investigated and evaluated in follow-up studies to reveal their potential in clinical practice.
- Klíčová slova
- Breast cancer, MicroRNA, U6 snRNA, let-7c, miR-182, miR-200c, miR-328, miR-451a, miR-454, miR-493,
- MeSH
- dospělí MeSH
- invazivní růst nádoru MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfatické metastázy MeSH
- mikro RNA * genetika MeSH
- nádorové biomarkery * genetika MeSH
- nádory prsu * genetika patologie MeSH
- prognóza MeSH
- regulace genové exprese u nádorů MeSH
- RNA malá jaderná * genetika MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- mikro RNA * MeSH
- MIRN155 microRNA, human MeSH Prohlížeč
- Mirn182 microRNA, human MeSH Prohlížeč
- MIRN451 microRNA, human MeSH Prohlížeč
- MIRN455 microRNA, human MeSH Prohlížeč
- mirnlet7 microRNA, human MeSH Prohlížeč
- nádorové biomarkery * MeSH
- RNA malá jaderná * MeSH
- U6 small nuclear RNA MeSH Prohlížeč
BACKGROUND: Breast cancer is the most commonly occurring cancer worldwide and is the main cause of death from cancer in women. Novel biomarkers are highly warranted for this disease. OBJECTIVE: Evaluation of novel long non-coding RNAs biomarkers for breast cancer. METHODS: The study comprised the analysis of the expression of 71 candidate lncRNAs via screening, six of which (four underexpressed, two overexpressed) were validated and analyzed by qPCR in tumor tissues associated with NST breast carcinomas, compared with the benign samples and with respect to their clinicopathological characteristics. RESULTS: The results indicated the tumor suppressor roles of PTENP1, GNG12-AS1, MEG3 and MAGI2-AS3. Low levels of both PTENP1 and GNG12-AS1 were associated with worsened progression-free and overall survival rates. The reduced expression of GNG12-AS1 was linked to the advanced stage. A higher grade was associated with the lower expression of PTENP1, GNG12-AS1 and MAGI2-AS3. Reduced levels of both MEG3 and PTENP1 were linked to Ki-67 positivity. The NRSN2-AS1 and UCA1 lncRNAs were overexpressed; higher levels of UCA1 were associated with multifocality. CONCLUSIONS: The results suggest that the investigated lncRNAs may play important roles in breast cancer and comprise a potential factor that should be further evaluated in clinical studies.
- Klíčová slova
- Breast cancer, GNG12-AS1, MAGI2-AS3, MEG3, NRSN2-AS1, PTENP1, UCA1, clinical outcomes, long non-coding RNAs,
- MeSH
- adaptorové proteiny signální transdukční genetika metabolismus MeSH
- dospělí MeSH
- guanylátkinasy genetika metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery * genetika metabolismus MeSH
- nádory prsu * genetika patologie metabolismus mortalita MeSH
- prognóza MeSH
- regulace genové exprese u nádorů MeSH
- RNA dlouhá nekódující * genetika MeSH
- senioři MeSH
- stupeň nádoru MeSH
- tumor supresorové geny MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- MAGI2 protein, human MeSH Prohlížeč
- MEG3 non-coding RNA, human MeSH Prohlížeč