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Circulating Micrornas Predict Survival of Patients with Tumors of Glial Origin.

ABSTRACT: The World Health Organization has recently introduced molecular prognostic-diagnostic biomarkers in the classification of Central Nervous System (CNS) tumors. In order to characterize subclasses of tumors that cannot find a precise location in the current classification, and, or cannot be tested because of scant material, it is important to find new molecular biomarkers in tissue and, or biological fluid samples. In this study, we identified serum microRNAs that could serve as biomarkers for the diagnosis and prognosis of patients with tumors of glial origin. We retrospectively analyzed microRNA expression in the serum extracellular vesicles of patients with tumors of glial origin. Extracellular vesicles RNA was analyzed by Nanostring. qRT-PCR confirmed 6 overexpressed microRNAs: hsa-miR-4443, hsa-miR-422a, hsa-miR-494-3p, hsa-miR-502-5p, hsa-miR-520f-3p, and hsa-miR-549a. Hsa-miR-4443 was the only microRNA that showed significant differences in most comparisons. In situ hybridization (ISH), confirmed that our signature was mostly expressed in cancer cells. Importantly, hsa-miR-549a and hsa-miR-502-5p expression predicted prognosis in patients with tumors of glial origin. Although more studies are needed, we demonstrated that serum vesicles microRNA profiles are promising diagnostic and prognostic molecular biomarkers that will find an actual application in the clinical practice of CNS tumors.

SUBMITTER: Drusco A

PROVIDER: S-EPMC5952410 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Objective:Klatskin tumors are rare, malignant tumors of the biliary system with a poor prognosis for patient survival. The current understanding of these tumors is limited to a small number of case reports or case series; therefore, we examined prognostic factors of this disease. Methods:A population cohort study was conducted in patients selected from the Surveillance, Epidemiology, and End Results (SEER) database with a Klatskin tumor that was histologically diagnosed between 2004 to 2014. Propensity-matching (PSM) analysis was performed to determine the overall survival (OS) among those with a Klatskin tumor (KCC), intrahepatic cholangiocarcinoma (ICCA), or hepatocellular carcinoma (HCC). The nomogram was based on 317 eligible Klatskin tumor patients and its predictive accuracy and discriminatory ability were determined using the concordance index (C-index). Results:Kaplan-Meier analysis showed that patients with Klatskin tumors had significantly worse overall survival rates (1-year OS = 26.2%, 2-year OS = 10.7%, 3-year OS = 3.4%) than those with intrahepatic cholangiocarcinoma (1-year OS = 62.2%, 2-year OS = 36.4%, 3-year OS = 19.1%, p < 0.001) or hepatocellular carcinoma (1-year OS = 72.4% , 2-year OS = 48.5%, 3-year OS = 36.2%, p < 0.001). A poor prognosis was also significantly associated with older age, higher grade, SEER historic stage, and lymph node metastasis. Local destruction of the tumor (HR = 0.635, 95% CI [0.421-0.956], p = 0.03) and surgery (HR = 0.434, 95% [CI 0.328-0.574], p < 0.001) were independent protective factors. Multivariate Cox analysis showed that older age, SEER historic stage, and lymph node metastases (HR = 1.468, 95% CI [1.008-2.139], p = 0.046) were independent prognostic factors of poor survival rates in Klatskin tumor patients, while cancer-directed surgery was an independent protective factor (HR = 0.555, 95% CI [0.316-0.977], p = 0.041). The prognostic and protective factors were included in the nomogram (C-index for survival = 0.651; 95% CI [0.607-0.695]). Conclusions:The Klatskin tumor group had poorer rates of OS and cancer-specific survival than the ICCA and HCC groups. Early detection and diagnosis were associated with a higher rate of OS in Klatskin tumor patients.

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Circulating Micrornas Predict Survival of Patients with Tumors of Glial Origin.

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