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Small RNA sequencing identified miR-3180 as a potential prognostic biomarker for Chinese hepatocellular carcinoma patients

ABSTRACT: MicroRNAs (miRNAs) and their target genes are aberrantly expressed in many cancers and are linked to carcinogenesis and metastasis, especially among hepatocellular carcinoma (HCC) patients. This study sought to identify new biomarkers related to HCC prognosis using small RNA sequencing from the tumor and matched normal adjacent tissue of 32 patients with HCC. Eight miRNAs were downregulated and 61 were upregulated more than twofold. Of these, five miRNAs, hsa-miR-3180, hsa-miR-5589-5p, hsa-miR-490-5p, hsa-miR-137, and hsa-miR-378i, were significantly associated with 5-year overall survival (OS) rates. Differential upregulation of hsa-miR-3180 and downregulation of hsa-miR-378i in tumor samples supported the finding that low and high concentrations of hsa-miR-3180 (p = 0.029) and hsa-miR-378i (p = 0.047), respectively, were associated with higher 5-year OS. Cox regression analyses indicated that hsa-miR‑3180 (HR = 0.08; p = 0.013) and hsa-miR‑378i (HR = 18.34; p = 0.045) were independent prognostic factors of poor survival. However, high hsa-miR‑3180 expression obtained larger AUCs for OS and progression-free survival (PFS) and had better nomogram prediction than hsa-miR‑378i. These findings indicate that hsa-miR‑3180 may be associated with HCC progression and could serve as a potential biomarker for this disease.

ORGANISM(S): Homo sapiens

PROVIDER: GSE227378 | GEO | 2023/03/20

REPOSITORIES: GEO

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Project description:Introduction: Several attempts have been made to expand the indications of liver transplantation for hepatocellular carcinoma (HCC) beyond Milan criteria. We aimed to define genomic features that enable the identification of patients with HCC beyond Milan criteria who have acceptable transplant outcomes. Methods: Among 770 consecutive HCC patients transplanted at Mount Sinai Hospital and Mayo Clinic between 1990 and 2013, 132 had tumors exceeding Milan criteria on pathology and were enrolled in the study. Explant tumors were analyzed to assess genomic signatures of poor prognosis and immunohistochemical markers associated with tumor recurrence and overall survival. Results: Most of the patients were males (80%) and HCV positive (71%) with a median age of 56. HCC beyond Milan criteria was defined pre-operative in 67%. On pathology, 44% of the patients satisfied the ‘up-to-7 rule’. At a median follow-up of 88 months, 64 patients had died and 45 recurred; the 5-year overall survival (OS) and recurrence rates were 57% and 35%, respectively. CK19 gene signature was independently associated with recurrence (HR=2.95, p<0.001), along with tumor size >5 cm (HR=3.37, p=0.023) and presence of satellite lesions (HR=2.98, p=0.001). S2 subclass signature, which is known to be associated with progenitor cell markers, was independently associated with poor OS (HR=3.18, p=0.001), along with tumor size >5 cm (HR=5.06, p<0.001) and outside up-to-seven rule (HR=2.50, p=0.002). Using the presence of markers of progenitor cells (either CK19 or S2 subclass signatures) patients may be classified into poor-prognosis (n=58; 5-year recurrence 53%, survival 45%) and good-prognosis subgroups (n=74; 5-year recurrence 19%, survival 67%) (HR=3.16, p<0.001 for recurrence, and HR=1.72, p=0.04 for OS). Conclusion: Gene signatures associated with progenitor cell markers (CK19 and S2 subclass signatures) define outcome of HCC patients beyond Milan criteria after transplantation. Patients without these signatures achieve survival rates similar as those patients within Milan criteria. Once prospectively validated, these markers may provide the rationale for a limited expansion of liver transplantation indications.

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Small RNA sequencing identified miR-3180 as a potential prognostic biomarker for Chinese hepatocellular carcinoma patients

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