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.

Dual transformation therapy for giant hepatocellular carcinoma: Two case reports and review of literature.

BACKGROUND: In the translational therapy of giant hepatocellular carcinoma (HCC), hepatic arterial infusion chemotherapy (HAIC) combined with anti-PD-1 immunotherapy and tyrosine kinase inhibitors (TKI) after laparoscopic portal vein ligation (PVL) is extremely rare. This is a dual conversion therapy that combines surgery and oncology. Here, we report two cases of successful surgical completion after dual conversion therapy. CASE SUMMARY: We report that a 54-year-old man and a 69-year-old woman were diagnosed with primary HCC combined with hepatitis B cirrhosis (case 2 also combined with fatty liver) on physical examination. Due to the insufficient residual liver volume assessed before surgery, laparoscopic right PVL was performed, followed by HAIC combined with anti-PD-1 immunotherapy and TKI. Finally, surgical resection was successfully completed, and pathology confirmed that the tumor was mostly necrotic (90%) in one case, and no live tumor tissue was found in the other case. CONCLUSION: In the process of surgical transformation, our treatment plan takes into account the control and transformation of oncology at the same time, which is expected to provide more opportunities for radical hepatectomy and improve the prognosis of patients with large liver cancer.

A radiomics model based on magnetic resonance imaging to predict cytokeratin 7/19 expression and liver fluke infection of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. HCC with liver fluke infection could harbor unique biological behaviors. This study was aimed at investigating radiomics features of HCC with liver fluke infection and establishing a model to predict the expression of cytokeratin 7 (CK7) and cytokeratin 19 (CK19) as well as prognosis at the same time. A total of 134 HCC patients were included. Gadoxetic acid-enhanced magnetic resonance imaging (MRI) images of all patients were acquired. Radiomics features of the tumor were extracted and then data dimensionality was reduced. The radiomics model was established to predict liver fluke infection and the radiomics score (Radscore) was calculated. There were 11 features in the four-phase combined model. The efficiency of the combined model increased significantly compared to each single-phase MRI model. Radscore was an independent predictor of liver fluke infection. It was also significantly different between different expression of CK7/ CK19. Meanwhile, liver fluke infection was associated with CK7/CK19 expression. A cut-off value was set up and all patients were divided into high risk and low risk groups of CK7/CK19 positive expression. Radscore was also an independent predictor of these two biomarkers. Overall survival (OS) and recurrence free survival (RFS) of negative liver fluke infection group were significantly better than the positive group. OS and RFS of negative CK7 and CK19 expression were also better, though not significantly. Positive liver fluke infection and CK19 expression prediction groups harbored significantly worse OS and RFS, survival of positive CK7 expression prediction was unsatisfying as well. A radiomics model was established to predict liver fluke infection among HCC patients. This model could also predict CK7 and CK19 expression. OS and RFS could be foreseen by this model at the same time.

Bile in bronchi: A case report.

BACKGROUND: The biliary bronchial fistula is rare and difficult to treat. Here we report a 49-year-old woman diagnosed with biliary bronchial fistula due to cough with yellow-green sputum. CASE PRESENTATION: this is a typical case of the biliary bronchial fistula with typical symptoms. The position of the abscess cavity below the diaphragm could not be catheter drainage. After anti-infection treatment, yellow-green sputum was reduced. Follow-up showed a good prognosis. CONCLUSION: biliary bronchial fistula is rare in the clinic, combined with chest and abdomen infection.

Oncogene UBE2I enhances cellular invasion, migration and proliferation abilities via autophagy-related pathway resulting in poor prognosis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a worldwide malignancy with high morbidity and mortality. In this study, ubiquitin conjugating enzyme E2I (UBE2I), a small ubiquitin-like modifier E2 enzyme reportedly expressed in tumors, was examined for its potential effects in HCC. Bioinformatics analysis was performed based on HCCDB, TIMER, and Kaplan-Meier plotter databases to explore the clinical implications in HCC. An siRNA kit was used to downregulate UBE2I, and in vitro experiments-including migration, invasion and proliferation assays-were performed to examine UBE2I expression in HCC. Western blot (WB) was used to determine whether downregulated UBE2I expression influenced the prognosis of HCC via autophagy pathways. Finally, RNA-sequencing was performed to explore candidate molecular mechanisms underlying the effect of UBE2I. Bioinformatics analysis including stratification by alcohol ingestion and hepatitis status in HCC showed that highly expressed UBE2I was not only correlated with poor prognosis, but was also associated with immune infiltrates. In vitro experiments showed that high expression of UBE2I was associated with increased migration, invasion and proliferation of HCC cells. WB results indicated that downregulated expression of UBE2I was associated with higher levels of autophagy-related proteins including LC3A/B, Beclin-1 and ATG16L1. Moreover, RNA-sequencing results suggested that UBE2I was involved in hepatocarcinogenesis, non-alcohol fatty liver disease, steatohepatitis, liver fibrosis, inflammation, hepatoblastoma, tumor angiogenesis, type 2 mellitus diabetes, biliary tract disease and other diseases. We conclude that oncogene UBE2I is associated with poor prognosis of HCC via autophagy pathways and may be involved in hepatocarcinogenesis, tumor angiogenesis, non-alcohol fatty liver disease and inflammation.