RESUMO
MicroRNA-200 (miR-200) family is highly expressed in ovarian cancer. We evaluated the levels of family members relative to the internal control miR-103a in ovarian cancer and control blood specimens collected from American and Hong Kong Chinese institutions, as well as from a laying hen spontaneous ovarian cancer model. The levels of miR-200a, miR-200b and miR-200c were significantly elevated in all human cancer versus all control blood samples. Further analyses showed significantly higher miR-200 levels in Chinese control (except miR-429) and cancer (except miR-200a and miR141) samples than their respective American counterparts. Subtype-specific analysis showed that miR-200b had an overall elevated level in serous cancer compared with controls, whereas miR-429 was significantly elevated in clear cell and endometrioid cancer versus controls. MiR-429 was also significantly elevated in cancer versus control in laying hen plasma samples, consistent with the fact that endometrioid tumor is the prevalent type in this species. A neural network model consisting of miR-200a/200b/429/141 showed an area under the curve (AUC) value of 0.904 for American ovarian cancer prediction, whereas a model consisting of miR-200b/200c/429/141 showed an AUC value of 0.901 for Chinese women. Hence, miR-200 is informative as blood biomarkers for both human and laying hen ovarian cancer.
Assuntos
Adenocarcinoma de Células Claras/patologia , Adenocarcinoma Mucinoso/patologia , Biomarcadores Tumorais/sangue , Cistadenocarcinoma Seroso/patologia , Neoplasias do Endométrio/patologia , MicroRNAs/genética , Neoplasias Ovarianas/patologia , Adenocarcinoma de Células Claras/sangue , Adenocarcinoma de Células Claras/genética , Adenocarcinoma Mucinoso/sangue , Adenocarcinoma Mucinoso/genética , Animais , Área Sob a Curva , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Galinhas , Cistadenocarcinoma Seroso/sangue , Cistadenocarcinoma Seroso/genética , Modelos Animais de Doenças , Neoplasias do Endométrio/sangue , Neoplasias do Endométrio/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/sangue , Pessoa de Meia-Idade , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/genéticaRESUMO
Cancer-related mortality of solid tumors remains the major cause of death worldwide. Circulating tumor DNA (ctDNA) released from cancer cells harbors specific somatic mutations. Sequencing ctDNA opens opportunities to non-invasive population screening and lays foundations for personalized therapy. In this study, two commercially available platforms, Roche's Avenio ctDNA Expanded panel and QIAgen's QIAseq Human Comprehensive Cancer panel were compared for (1) panel coverage of clinically relevant variants; (2) target enrichment specificity and sequencing performance; (3) the sensitivity; (4) concordance and (5) sequencing coverage using the same human blood sample with ultra-deep next-generation sequencing. Our finding suggests that Avenio detected somatic mutations in common cancers in over 70% of patients while QIAseq covered nearly 90% with a higher average number of variants per patient (Avenio: 3; QIAseq: 8 variants per patient). Both panels demonstrated similar on-target rate and percentage of reads mapped. However, Avenio had more uniform sequencing coverage across regions with different GC content. Avenio had a higher sensitivity and concordance compared with QIAseq at the same sequencing depth. This study identifies a unique niche for the application of each of the panel and allows the scientific community to make an informed decision on the technologies to meet research or application needs.