Background: Amyloid light-chain amyloidosis (AL amyloidosis) is commonly associated with multiple myeloma. However, the clinical characteristics and prognosis of symptomatic and smoldering multiple myeloma with AL amyloidosis are not particularly clear. Methods: Patients with symptomatic and smoldering multiple myeloma in the Peking University First Hospital registry from 2010 to 2018 were studied. The clinical and laboratory information was collected from first presentation to death or until the last available clinical follow-up. The patients’ survival and outcomes were analyzed, and the relationship between the clinical parameters and survival was also assessed. Results: Compared with symptomatic multiple myeloma patients without AL amyloidosis, patients with AL amyloidosis had higher incidence of BNP≧700pg/mL (P< 0.001), ALP> 187.5IU/L (P=0.032) and ALB< 25g/L (P< 0.001). Similarly, compared with smoldering multiple myeloma patients without AL amyloidosis, patients with AL amyloidosis had higher incidence of BNP≧700pg/mL (P=0.030) and Alb< 25g/L (P=0.024). The existence of AL amyloidosis, especially those with the heart involvement, was related to shorter long-term survival of symptomatic and smoldering multiple myeloma according to univariate analyses. Renal involvement and gastrointestinal tract involvement had an impact on the prognosis of smoldering multiple myeloma but not on the symptomatic multiple myeloma. Cox regression model for overall survival detected BNP≧700pg/mL in symptomatic multiple myeloma having independent poorer prognostic significance (HR=2.455, P=0.004). Interestingly, BNP at diagnosis was significantly correlated with cardiac amyloidosis (r=0.496, P< 0.001). Cox regression model for overall survival detected the presence of AL amyloidosis in smoldering multiple myeloma having independent poorer prognostic significance (HR=8.741, P=0.002). Conclusion: AL amyloidosis is an independent poor prognostic factor for not only symptomatic multiple myeloma but also smoldering multiple myeloma. It is mainly because of involvement of important organs, especially the heart. AL amyloidosis probably has a greater impact on the prognosis of smoldering multiple myeloma than on the symptomatic multiple myeloma.

DOK is a new type of regulatory protein family that participates in the regulation of tumor cell growth. However, most of the studies are conducted in cell lines, and systematic studies have not been conducted in human tumors. We conducted a comprehensive analysis of DOK based on its expression profile and its relationship with patient survival, immune infiltration, tumor microenvironment, and drug sensitivity. We used the TCGA database to analyze the correlation between DOK family gene expression and prognosis and clinical stage. The protein expression of DOK in tumor tissues was analyzed by immunohistochemistry. Use the cBioPortal database to analyze the alteration frequency in DOK family genes in human tumors. In addition, we used ESTIMATE algorithm and TIMER website to analyze the correlation between DOK family genes and tumor immunity. Finally, we further analyzed the relationship between DOK family genes and tumor stemness and the sensitivity of cancer cells to chemotherapy. We conducted a comprehensive analysis of DOK family genes based on its expression profile and its relationship with patient survival. We also confirmed this conclusion by immunohistochemistry. The expression of DOK family genes is related to OS, clinical stage, tumor mutation, methylation, CNV, and SNV. DOK family genes are significantly associated with poor prognosis of UVM. DOK1-DOK3 has obvious correlation with tumor immunity. DOK2 can increase the sensitivity of chemotherapy drugs, while DOK4 reduces the sensitivity of multiple chemotherapy drugs. In addition, the expression level of DOK family genes is significantly correlated with the activity of cancer marker-related pathways. DOK plays a role of tumor suppressor gene or tumor-promoting gene in different tumors. However, DOK family genes play a role in promoting cancer in UVM. DOK family genes are significantly associated with drug sensitivity.

Uridine is a key metabolite used as a substrate for the production of DNA, RNA, and glucose, and it is mainly synthesized in the liver. Currently, it is not known whether uridine levels are altered in the tumor microenvironment of patients with hepatocellular carcinoma (HCC) and whether uridine can be a target for tumor therapy. In this study, the detection of genes associated with de novo uridine synthesis, carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, dihydroorotase (CAD) (n = 115), and dihydroorotate dehydrogenase (DHODH) (n = 115) in HCC tissues through tissue microarrays revealed that the expression of CAD and DHODH was higher in tumor compared with paraneoplastic tissues. Next, we collected tumor tissues from surgically resected HCC patients and the corresponding adjacent non-tumor tissues (n = 46) for LC–MS/MS assays. The results showed that the median and interquartile ranges of uridine content in non-tumor and tumor tissues were 640.36 (504.45–807.43) and 484.22 (311.91–626.73) nmol/g, respectively. These results suggest that uridine metabolism is disturbed in HCC patients. To further investigate whether uridine can be used as a tumor-therapeutic target, a series of high concentrations of uridine were incubated with HCC cells in vitro and in vivo. It was observed that uridine dose-dependently inhibited the proliferation, invasion, and migration of HCC cells by activating the ferroptosis pathway. Overall, these results reveal for the first time the range of uridine content in human HCC tissues and suggest that uridine may be a new target for HCC therapy.

Hepatocellular carcinoma (HCC) is an aggressive malignant tumor with a poor prognosis. Reactive oxygen species (ROS) play an important role in tumors; however, the role of ROS‐related genes is still unclear in HCC. Therefore, we analyzed the role of ROS‐related genes in HCC via bioinformatics methods. Firstly, a prognosis model was constructed using LASSO Cox regression and multivariate analyses. We also investigated the potential function of the ROS‐related genes and the correlation with immune infiltration, tumor stemness, and drug sensitivity. ICGC database was used for validation. Secondly, we further analyzed the role of 11 ROS‐related genes in HCC. As a member of ROS gene family, the role of STK25 has remained unclear in HCC. We explored the biological function of STK25 using in vitro experiments. The present study was the first to construct a ROS‐related prognostic model in HCC. The correlation of ROS‐related genes with immune infiltration, tumor stemness, and drug sensitivity was dissected. Furthermore, we demonstrated that STK25 knockdown could increase the proliferation, migration, and invasion capacity of HCC cells.

Background: Multiple myeloma causes different types of renal injury. C3 glomerulonephritis (C3GN) is characterised by an abnormal deposition of complement C3 in the glomeruli due to abnormal activation of the alternative pathway of the complement system. While the association between C3GN and multiple myeloma has been well established, mild renal injury by C3GN in multiple myeloma patients with high levels of light chain has not been reported.Case presentation: A 55-year-old Chinese man presented with proteinuria. Combined with immunofixation electrophoresis, bone marrow biopsy, and renal biopsy, he was diagnosed with IgA-type multiple myeloma accompanied by C3GN and light chain proximal tubulopathy without crystal deposits. Although he had a higher level of lambda serum-free light chain, the renal injury in this patient was mild. After treatment with four courses of BD, one course of PAD, and autologous stem cell transplantation, he achieved a very good partial hematologic response with stable renal function.Conclusions: In multiple myeloma, the light chain reaches a certain level and persists, resulting in C3GN renal impairment. Early diagnosis and early intensive treatment are critical for the prognosis of such patients.