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BACKGROUND: The hepatocellular carcinoma (HCC) incident rate is gradually increasing yearly despite all the research and efforts taken by scientific communities and governing bodies. Approximately 90% of all liver cancer cases belong to HCC. Usually, HCC patients approach the treatment in the late stages of this malignancy which becomes the primary cause of high mortality rate. The knowledge about molecular pathogenesis of HCC is limited and needs more attention from researchers to identify the driver genes and miRNAs, which causes to translate this information into clinical practice. Therefore, the key regulators identification of miRNA-mRNA regulatory network is essential to identify HCC-associated genes. METHODOLOGY: We extracted microRNA (miRNA) and messenger RNA (mRNA) expression datasets of normal and tumor HCC patient samples from UCSC Xena followed by identifying differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs). Univariate and multivariate cox-proportional hazard models were utilized to identify DEMs having significant association with overall survival (OS). Kaplan-Meier (KM) plotter was used to validate the presence of prognostic DEMs. A risk-score model was used to evaluate the effectiveness of KM-plotter validated DEMs combination on risk of samples. Target DEGs of prognostic miRNAs were identified via sources such as miRTargetLink and miRWalk followed by their validation in an external microarray cohort and enrichment analysis. RESULTS: 562 DEGs and 388 DEMs were identified followed by seven prognostic miRNAs (i.e., miR-19a, miR-19b, miR-30d-5p, miR-424-5p, miR-3677-5p, miR-3913-5p, miR-7705) post univariate, multivariate, risk-score model evaluation and KM-plotter analyses. ANLN, MRO, CPEB3 were their targets and were also validated in GSE84005 dataset. CONCLUSIONS: The findings of this study decipher that most significant miRNAs and their identified target genes have association with apoptosis, inflammation, cell cycle regulation and cancer-related pathways, which appear to contribute to HCC pathogenesis and therefore, the discovery of new targets.
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Background/Objective: To report a case of adenomyosis in a woman with hyperprolactinemia which resolved after initiation of dopamine agonist therapy. Case Report: A 35-year-old woman with a history of Graves' disease was referred for evaluation of hyperthyroidism in March 2020. She was started on methimazole and thyroid function normalized. The patient also had a history of a pituitary microadenoma and was previously treated with cabergoline which was stopped after 12 months as she became pregnant.In July 2020, the patient began to have polymenorrhea. Hyperprolactinemia was thought to be an unlikely cause as it most often causes hypogonadotropic hypogonadism with amenorrhea. A pelvic ultrasound demonstrated a bulky uterus with adenomyosis. Gynecology recommended treating adenomyosis by lowering her prolactin levels. She was started on cabergoline 0.25 mg weekly in October 2021. Within 2 months of initiation of cabergoline, she had resolution of symptoms and radiological resolution of adenomyosis. Discussion: Prolactin has been implicated in the pathogenesis of adenomyosis, endometriosis and leiomyomas suggesting that a decrease in prolactin levels may suppress these lesions. The pathogenesis of adenomyosis has been related to direct prolactin effects in the promotion of gland/cell proliferation and function. Conclusion: We conclude that prolonged elevation in prolactin may result in the development of adenomyosis and subsequent prolonged abnormal uterine bleeding. Dopamine agonists, like cabergoline, inhibit the synthesis and secretion of prolactin from the pituitary gland and may have a role in the management of adenomyosis in patients with hyperprolactinemia.