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Nasopharyngeal carcinoma (NPC) is endemic in Southern China and Southeast Asia. Hyperthermia is widely used in combination with chemotherapy and radiotherapy to enhance therapeutic efficacy in NPC treatment, but the underlying anti-tumor mechanisms of hyperthermia remain unclear. Complement C3 has been reported to participate in the activation of immune system in the tumor microenvironment, leading to tumor growth inhibition. In this study, we aimed to explore the effect and mechanisms of hyperthermia and investigate the functional role of complement C3 in NPC hyperthermia therapy (HT). The serum levels of complement C3 before and after hyperthermia therapy in patients with NPC were analyzed. NPC cell lines SUNE1 and HONE1 were used for in vitro experiment to evaluate the function of complement C3 and HT on cell proliferation and apoptosis. SUNE1 xenograft mouse model was established and tumor-bearing mice were treated in water bath at a constant temperature of 43°C. Tumor samples were collected at different time points to verify the expression of complement C3 by immunohistochemical staining and western blot. The differential expressed genes after hyperthermia were analyzed by using RNA sequencing. We found that complement could enhance hyperthermia effect on suppressing proliferation and promoting apoptosis of tumor cells in NPC. Hyperthermia decreased the mRNA expression of complement C3 in tumor cells, but promoted the aggregation and activation circulating C3 in NPC tumor tissue. By using in vitro hyperthermia-treated NPC cell lines and SUNE1 xenograft tumor-bearing mice, we found that the expression of heat shock protein 5 (HSPA5) was significantly upregulated. Knockdown of HSPA5 abrogated the anti-tumor effect of hyperthermia. Moreover, we demonstrated that hyperthermia downregulated CD55 expression via HSPA5/NFκB (P65) signaling and activated complement cascade. Our findings suggest that therapeutic hyperthermia regulates complement C3 activation and suppresses tumor development via HSPA5/NFκB/CD55 pathway in NPC. Complement was involved in the anti-tumor effect of hyperthermia in vitro. Hyperthermia markedly increased the expression of heat shock protein 5 (HSPA5) and decreased the expression of CD55 which regulated the activation of complement C3 and complement cascade. Activation of HSPA5/NFκB (P65) signaling pathway resulted in a decrease in CD55 expression. [ABSTRACT FROM AUTHOR]

Background: Recently, experts proposed subclassification for BCLC B patients. In this study, we aimed to evaluate the efficient of subclassification of patients with hepatitis B virus-related hepatocellular carcinoma (HCC) in Barcelona Clinic Liver Cancer (BCLC) staging system., Methods: Seven hundred twenty-nine consecutive hepatitis B virus-related HCC patients with BCLC stage B classification who underwent hepatectomy in the period 2006-2012 were retrospectively analyzed. Patients were reclassified based on the new proposed subclassification of the BCLC B stage from B1 to B4. The prognosis of subclassification was tested using Kaplan-Meier statistics analysis., Results: There were 145 (19.9%), 480 (65.8%), 62 (8.5%), and 42 (5.8%) patients in B1, B2, B3, and B4, respectively. The result suggested that overall and tumor-free survival rates among the B1, B2, and B3 subclassification in the Bolondi system had significant difference (P < 0.05). However, no significant difference was found between B3 and B4 subclassifications. Cox regression showed that BCLC B subclassification, largest/smallest diameter, and anatomic liver resection were independent predictors of tumor-free survival. BCLC B subclassification and anatomic liver resection were independent predictors of overall survival., Conclusions: The subclassification of BCLC stage B can be used in patients with HBV-related HCC who underwent curative intent hepatectomy. Patients in BCLC B1 and B2 subgroups should be treated more aggressively than patients in B3 and B4 subgroups. B3 and B4 groups should be merged for patients with HBV-related HCC who underwent curative intent hepatectomy.