Case Report: A case of hepatocellular carcinoma with aberrant right hepatic artery treated with transarterial chemoembolization and infusion chemotherapy separately to bilobar lesion combining with systemic therapies and sequential hepatectomy.

Background: Hepatocellular carcinoma (HCC) with a dismal prognosis is the second most deadly malignancy globally. Surgery is believed to be a curative approach. Nevertheless, there is still a considerable probability of postoperative recurrence. Most patients present in advanced stages with a surgically and oncologically unresectable disease. Systemic medicines are increasingly important to downstage the disease and further improve survival. Case summary: A 67-year-old Chinese man with uncontrolled hepatitis B was discovered to have liver masses with abnormal serum vitamin K absence or antagonist-II (PIVKA-II) level during checkup for upper abdominal discomfort. Abdominal multiphase computerized tomography (CT) and gadoxetate disodium-enhanced magnetic resonance imaging (MRI) showed the bulky bilobar HCCs of Barcelona Clinic Liver Cancer stage B and China Liver Cancer Staging stage IIa. Furthermore, the aberrant right hepatic artery (RHA) originates from the superior mesenteric artery. Due to the location being adjacent to important vasculatures and massive size of the right-sided lesion, curative resection appears to be challenging. To achieve a favorable surgical margin, repeated hepatic arterial infusion chemotherapy (HAIC) was adopted through the variant RHA, while transarterial chemoembolization (TACE) was delivered to the left lobe to arrest tumor growth. Furthermore, sintilimab plus lenvatinib served as the sequential systemic therapy. After 5 months of conversion treatment, the partial response with a decreased serum PIVKA-II level was attained. The R0 hepatectomy was then performed without postoperative complications. The immunohistochemistry and next-generation sequencing results suggested that the two-side HCCs existing tumor heterogeneity were not completely consistent. The patient continues to be without evidence of disease. Conclusion: Our case highlights a favorable outcome in a man with bilobar bulky HCC after undergoing the comprehensive therapeutic schedule that includes personalized intervention and systemic drug therapy. In terms of conversion therapy, our case provides a secure and practical reference for managing unresectable bilobar HCC coexisting with the aberrant hepatic artery.

Clinical implications and molecular mechanisms of Cyclin-dependent kinases 4 for patients with hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) was frequently considered as a kind of malignant tumor with a poor prognosis. Cyclin-dependent kinases (CDK) 4 was considered to be cell-cycle-related CDK gene. In this study, we explored the clinical significance of CDK4 in HCC patients. METHODS: Data of HCC patients were obtained from The Cancer Genome Atlas database (TCGA) and the Gene Expression Omnibus (GEO) database. Kaplan-Meier analysis and Cox regression model were performed to calculate median survival time (MST) and the hazard ration (HR), respectively. The joint-effect analysis and prognostic risk score model were constructed to demonstrate significance of prognosis-related genes. The differential expression of prognostic genes was further validated using reverse transcription-quantitative PCR (RT-qPCR) of 58 pairs of HCC samples. RESULTS: CDK1 and CDK4 were considered prognostic genes in TCGA and GSE14520 cohort. The result of joint-effect model indicated patients in CDK1 and CDK4 low expression groups had a better prognosis in TCGA (adjusted HR = 0.491; adjusted P = 0.003) and GSE14520 cohort (adjusted HR = 0.431; adjusted P = 0.002). Regarding Kaplan-Meier analysis, high expression of CDK1 and CDK4 was related to poor prognosis in both the TCGA (P < 0.001 and = 0.001 for CDK1 and CDK4, respectively) and the GSE14520 cohort (P = 0.006 and = 0.033 for CDK1 and CDK4, respectively). However, only CDK4 (P = 0.042) was validated in RT-qPCR experiment, while CDK1 (P = 0.075) was not. CONCLUSION: HCC patients with high CDK4 expression have poor prognosis, and CDK4 could be a potential candidate diagnostic biomarker for HCC.

High-Mobility Group AT-Hook 1 Served as a Prognosis Biomarker and Associated with Immune Infiltrate in Hepatocellular Carcinoma.

BACKGROUND: The protein high-mobility group AT-hook 1 (HMGA1) has been demonstrated that modulated cellular proliferation, invasion, and apoptosis with a poor prognosis in miscellaneous carcinomas. However, the mechanism of circumstantial carcinogenesis and association with the immune microenvironment of HMGA1 in hepatocellular carcinoma (HCC) had not been extensively explored. METHODS: The gene expression, clinicopathological correlation, and prognosis analysis were performed in the data obtained from TCGA. The results were further validated by ICGC and GEO database and external validation cohort from Guangxi. The HMGA1 protein expression was further examined in the HPA database. Biological function analyses were conducted by GSEA, STRING database, and Coexpedia online tool. Using TIMER and CIBERSORT method, the relationship between immune infiltrate and HMGA1 was investigated. RESULTS: In HCC, HMGA1 had much higher transcriptional and proteomic expression than in corresponding paraneoplastic tissue. Patients with high HMGA1 expression had a poor prognosis and unpromising clinicopathological features. High HMGA1 expression was closely related to the cell cycle, tumorigenesis, substance metabolism, and immune processes by regulating complex signaling pathways. Notably, HMGA1 may be associated with TP53 mutational carcinogenesis. Moreover, increased HMGA1 expression may lead to an increase in immune infiltration and a decrease in tumor purity in HCC. CIBERSORT analysis elucidated that the amount of B cell naive, B cell memory, T cells gamma delta, macrophages M2, and mast cell resting decreased when HMGA1 expression was high, whereas T cells follicular helper, macrophages M0, and Dendritic cells resting increased. CONCLUSION: In conclusions, HMGA1 is a potent prognostic biomarker and a sign of immune infiltration in HCC, which may be a potential immunotherapy target for HCC.