Analysis for drug metabolism-related prognostic subtypes and gene signature in liver cancer.

Liver cancer is highly heterogeneous and has a poor prognosis. We aimed to identify a drug metabolism-related prognostic subtype and a gene signature as references for prognosis and therapy options for patients with liver cancer. Patient information was collected from online databases. Drug metabolism-related genes were obtained from previous studies and were used to screen differentially expressed prognostic genes. The patients were divided into different clusters and differences in clinical features, immunity, pathways and therapy responses between the clusters were analyzed. LASSO analysis was performed to identify the optimal prognostic genes and establish a risk score model. Finally, the risk score distribution in different subtypes was investigated. A total of 54 prognostic genes were identified to categorize the patients into cluster 1 and cluster 2. Cluster 1 showed worse survival than cluster 2, and cluster 1 also showed high levels of malignancy. Furthermore, cluster 1 exhibited a higher TIDE (tumor immune dysfunction and exclusion) score and lower IC50 response to paclitaxel, gemcitabine and camptothecin, indicating that cluster 1 individuals may derive more benefit from immunotherapy but less benefit from chemotherapy. The risk score, based on the six optimal prognostic genes, demonstrated an adequate prognostic capability. The high-risk group showed worse survival; meanwhile, cluster 1 contained the majority of high-risk samples. Our results should be useful for prognosis and specific therapy for patients with liver cancer. Patients with the features of cluster 1 and a high risk score will tend to exhibit worse survival. Furthermore, immunotherapy may be more suitable for cluster 1-type patients while chemotherapy may be more suitable for cluster 2 patients.

Enhancement of NK cells proliferation and function by Shikonin.

CONTEXT: Shikonin is a kind of naphthoquinone compound found mainly in Lithospermum erythrorhizon Sieb,et Zucc. Previous studies have shown that Shikonin has anti-tumor, anti-inflammatory and extensive pharmacological effects. According to new studies, Shikonin could also modulate the immune system function, but the effect to NK (nature killer) cells is yet unknown. OBJECTIVE: To investigate the effect and mechanism of Shikonin on NK cells proliferation and cytotoxicity to colon cancer cell line (Caco-2). METHODS: The proliferation and cytotoxicity of NK cells cultured with Shikonin were detected with CCK-8 assay. The expressions of perforin, GranB and IFN-γ were examined with FCM. The content of TNF-alpha was disclosed with ELISA kit. p-ERK1/2 and p-Akt expression of NK cells were detected with western blot. RESULTS: With CCK-8 assay, it is found that Shikonin could significantly enhance NK cells proliferation and cytotoxicity to colon cancer cells. With FCM assay, it is found that Shikonin could improve the expression of perforin and GranB in a dose-dependent manner. Shikonin had no effect on TNF-alpha and IFN-γ expression. In mechanism, the study shows that Shikonin could enhance the expression of p-ERK1/2 and p-Akt. CONCLUSIONS: Shikonin enhances NK cells proliferation and cytotoxicity via the improvement of perforin, GranB, p-ERK1/2 and p-Akt expression.

Both FOXP1 and p65 expression are adverse risk factors in diffuse large B-cell lymphoma: a retrospective study in China.

The purpose of this study was to investigate the clinical significance of FOXP1 and p65 expression in diffuse large B-cell lymphoma (DLBCL). Immunohistochemistry was performed to determine the expression of FOXP1 and p65 protein in 92 DLBCL tissues and analyze their correlations with clinicopathological features or prognosis of patients. The survival was assessed by the Kaplan-Meier method and proportional hazards model. Results showed that positive FOXP1 expression was detected in 68 (73.9%) cases and positive p65 expression was detected in 56 (60.9%) cases. There were 46 (50.0%) co-expression of FOXP1 and p65 protein in all cases, a positive correlation between the expression of FOXP1 and p65 was noted (r=0.234, p=0.025). The status of FOXP1 was correlated with patient's age, worse performance status score, higher lactate dehydrogenase levels and International Prognostic Index (IPI) factor score. The status of p65 was correlated with patient's age, B symptom and higher IPI factor scores. Both FOXP1 and p65 protein expression were associated with the non-GCB phenotype (p=0.001 or 0.000). The Kaplan-Meier curves showed that both FOXP1 and p65 expression were associated with poor survival of patients. Meanwhile, FOXP1+/p65+ subgroup had the worst PFS (p=0.012) and OS (p=0.030), whereas the FOXP1-/p65- subgroup had the best prognosis. Thus, immunohistochemical assessment of both FOXP1 and p65 status in DLBCL tissues may be a valuable approach for predicting the survival of DLBCL patients.

Relationship between RGS5 expression and differentiation and angiogenesis of gastric carcinoma.

AIM: To explore the regulator of G-protein signaling 5 (RGS5) expression in gastric carcinoma and its association with differentiation and microvascular density (MVD). METHODS: Expression of RGS5 and CD34 were examined in 76 cases of gastric carcinoma, including 22 cases with lymph node metastasis and 54 cases without lymph node metastasis determined by immunohistochemistry (IHC). MVD was assessed using CD34 monoclonal antibody. The presence of RGS5 and CD34 was analyzed by IHC using the Envision technique. RESULTS: The RGS5 expression in gastric carcinoma was positively correlated with the differentiation of the tumor (r = 0.345, P < 0.001), but not related with age, gender, tumor size, clinical stage and lymph node metastasis (P > 0.05). The average MVD in the group with lymph node metastasis was significantly higher than that in the group without lymph node metastasis (P < 0.05). RGS5 expression was negatively correlated with the average MVD (P < 0.05). CONCLUSION: RGS5 expression level in gastric carcinoma is associated with the differentiation and MVD of the tumor, and may be used as an important parameter for determining the prognosis of gastric carcinoma patients.