A novel panel of clinically relevant miRNAs signature accurately differentiates oral cancer from normal mucosa
IntroductionAlthough a considerable body of knowledge has been accumulated regarding the early diagnosis and treatment of oral squamous cell carcinoma (OSCC), its survival rates have not improved over the last decades. Thus, deciphering the molecular mechanisms governing oral cancer will support the...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-12-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.1072579/full |
| _version_ | 1797987662497316864 |
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| author | Nikolay Mehterov Nikolay Mehterov Andrea Sacconi Claudio Pulito Boyan Vladimirov Georgi Haralanov Dimitar Pazardjikliev Boyan Nonchev Ioana Berindan-Neagoe Giovanni Blandino Victoria Sarafian Victoria Sarafian |
| author_facet | Nikolay Mehterov Nikolay Mehterov Andrea Sacconi Claudio Pulito Boyan Vladimirov Georgi Haralanov Dimitar Pazardjikliev Boyan Nonchev Ioana Berindan-Neagoe Giovanni Blandino Victoria Sarafian Victoria Sarafian |
| author_sort | Nikolay Mehterov |
| collection | DOAJ |
| description | IntroductionAlthough a considerable body of knowledge has been accumulated regarding the early diagnosis and treatment of oral squamous cell carcinoma (OSCC), its survival rates have not improved over the last decades. Thus, deciphering the molecular mechanisms governing oral cancer will support the development of even better diagnostic and therapeutic strategies. Previous studies have linked aberrantly expressed microRNAs (miRNAs) with the development of OSCC.MethodsWe combined bioinformatical and molecular methods to identify miRNAs with possible clinical significance as biomarkers in OSCC. A set of 10 miRNAs were selected via an in silico approach by analysing the 3’untranslated regions (3’UTRs) of cancer-related mRNAs such as FLRT2, NTRK3, and SLC8A1, TFCP2L1 and etc. RT-qPCR was used to compare the expression of in silico identified miRNAs in OSCC and normal tissues (n=32).ResultsAmong the screened miRNAs, miR-21-5p (p < 0.0001), miR-93-5p (p < 0.0197), miR-146b-5p (p <0.0012), miR-155-5p (p < 0.0001), miR-182-5p (p < 0.0001) were significantly overexpressed, whereas miR-133b (p < 0.05) was significantly downregulated in OSCC tissues, a scenario confirmed in two additional OSCC validation cohorts: Regina Elena National Cancer Institute (IRE cohort, N=74) and The Cancer Genome Atlas Data Portal (TCGA cohort, N=354). Initial stage tumors (T1, T2) expressed significantly higher levels of miR-133b (p < 0.0004) compared to more advanced ones (T3, T4). Also, we identified miR-93-5p (p < 0.0003), miR-133b (p < 0.0017) and miR-155-5p (p < 0.0004) as correlated with HPV-induced OSCC. The high expression of these 6 miRNAs as a signature predicted shorter disease-free survival (DFS) and could efficiently distinguish OSCC cases from healthy controls with areas under the curve (AUC) of 0.91 with sensitivity and specificity of 0.98 and 0.6, respectively. Further target identification analysis revealed enrichment of genes involved in FOXO, longevity, glycan biosynthesis and p53 cancer-related signaling pathways. Also, the selected targets were underexpressed in OSCC tissues and showed clinical significance related to overall survival (OS) and DFS.DiscussionOur results demonstrate that a novel panel consisting of miR-21-5p, miR-93-5p, miR-133b, miR-146b-5p, miR-155-5p and miR-182-5p could be used as OSCC-specific molecular signature with diagnostic and prognostic significance related to OS and DFS. |
| first_indexed | 2024-04-11T07:50:49Z |
| format | Article |
| id | doaj.art-b667dfb9107c43b6a652b870abdc7a85 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-11T07:50:49Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-b667dfb9107c43b6a652b870abdc7a852022-12-22T04:36:05ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-12-011210.3389/fonc.2022.10725791072579A novel panel of clinically relevant miRNAs signature accurately differentiates oral cancer from normal mucosaNikolay Mehterov0Nikolay Mehterov1Andrea Sacconi2Claudio Pulito3Boyan Vladimirov4Georgi Haralanov5Dimitar Pazardjikliev6Boyan Nonchev7Ioana Berindan-Neagoe8Giovanni Blandino9Victoria Sarafian10Victoria Sarafian11Department of Medical Biology, Medical University-Plovdiv, Plovdiv, BulgariaResearch Institute, Medical University-Plovdiv, Plovdiv, BulgariaUOSD Clinical Trial Center, Biostatistics and Bioinformatics, IRCCS Regina Elena National Cancer Institute, Rome, ItalyTranslational Oncology Research Unit, Department of Research, Advanced Diagnostic, and Technological Innovation, IRCCS, Regina Elena National Cancer Institute, Rome, ItalyDepartment of Maxillofacial Surgery, Medical University-Plovdiv, Plovdiv, BulgariaDepartment of Maxillofacial Surgery, Medical University-Plovdiv, Plovdiv, BulgariaDepartment of Otorhinolaryngology, Medical University-Plovdiv, Plovdiv, BulgariaDepartment of Endocrinology, Medical University-Plovdiv, Plovdiv, BulgariaResearch Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, RomaniaTranslational Oncology Research Unit, Department of Research, Advanced Diagnostic, and Technological Innovation, IRCCS, Regina Elena National Cancer Institute, Rome, ItalyDepartment of Medical Biology, Medical University-Plovdiv, Plovdiv, BulgariaResearch Institute, Medical University-Plovdiv, Plovdiv, BulgariaIntroductionAlthough a considerable body of knowledge has been accumulated regarding the early diagnosis and treatment of oral squamous cell carcinoma (OSCC), its survival rates have not improved over the last decades. Thus, deciphering the molecular mechanisms governing oral cancer will support the development of even better diagnostic and therapeutic strategies. Previous studies have linked aberrantly expressed microRNAs (miRNAs) with the development of OSCC.MethodsWe combined bioinformatical and molecular methods to identify miRNAs with possible clinical significance as biomarkers in OSCC. A set of 10 miRNAs were selected via an in silico approach by analysing the 3’untranslated regions (3’UTRs) of cancer-related mRNAs such as FLRT2, NTRK3, and SLC8A1, TFCP2L1 and etc. RT-qPCR was used to compare the expression of in silico identified miRNAs in OSCC and normal tissues (n=32).ResultsAmong the screened miRNAs, miR-21-5p (p < 0.0001), miR-93-5p (p < 0.0197), miR-146b-5p (p <0.0012), miR-155-5p (p < 0.0001), miR-182-5p (p < 0.0001) were significantly overexpressed, whereas miR-133b (p < 0.05) was significantly downregulated in OSCC tissues, a scenario confirmed in two additional OSCC validation cohorts: Regina Elena National Cancer Institute (IRE cohort, N=74) and The Cancer Genome Atlas Data Portal (TCGA cohort, N=354). Initial stage tumors (T1, T2) expressed significantly higher levels of miR-133b (p < 0.0004) compared to more advanced ones (T3, T4). Also, we identified miR-93-5p (p < 0.0003), miR-133b (p < 0.0017) and miR-155-5p (p < 0.0004) as correlated with HPV-induced OSCC. The high expression of these 6 miRNAs as a signature predicted shorter disease-free survival (DFS) and could efficiently distinguish OSCC cases from healthy controls with areas under the curve (AUC) of 0.91 with sensitivity and specificity of 0.98 and 0.6, respectively. Further target identification analysis revealed enrichment of genes involved in FOXO, longevity, glycan biosynthesis and p53 cancer-related signaling pathways. Also, the selected targets were underexpressed in OSCC tissues and showed clinical significance related to overall survival (OS) and DFS.DiscussionOur results demonstrate that a novel panel consisting of miR-21-5p, miR-93-5p, miR-133b, miR-146b-5p, miR-155-5p and miR-182-5p could be used as OSCC-specific molecular signature with diagnostic and prognostic significance related to OS and DFS.https://www.frontiersin.org/articles/10.3389/fonc.2022.1072579/fulloral squamous cell carcinomabiomarkermiRNAmRNAoverall survivaldisease-free survival |
| spellingShingle | Nikolay Mehterov Nikolay Mehterov Andrea Sacconi Claudio Pulito Boyan Vladimirov Georgi Haralanov Dimitar Pazardjikliev Boyan Nonchev Ioana Berindan-Neagoe Giovanni Blandino Victoria Sarafian Victoria Sarafian A novel panel of clinically relevant miRNAs signature accurately differentiates oral cancer from normal mucosa Frontiers in Oncology oral squamous cell carcinoma biomarker miRNA mRNA overall survival disease-free survival |
| title | A novel panel of clinically relevant miRNAs signature accurately differentiates oral cancer from normal mucosa |
| title_full | A novel panel of clinically relevant miRNAs signature accurately differentiates oral cancer from normal mucosa |
| title_fullStr | A novel panel of clinically relevant miRNAs signature accurately differentiates oral cancer from normal mucosa |
| title_full_unstemmed | A novel panel of clinically relevant miRNAs signature accurately differentiates oral cancer from normal mucosa |
| title_short | A novel panel of clinically relevant miRNAs signature accurately differentiates oral cancer from normal mucosa |
| title_sort | novel panel of clinically relevant mirnas signature accurately differentiates oral cancer from normal mucosa |
| topic | oral squamous cell carcinoma biomarker miRNA mRNA overall survival disease-free survival |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.1072579/full |
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