The identification of circulating proteins associated with acquired immunodeficiency syndrome‐related non‐Hodgkin lymphoma (AIDS‐NHL) may help in the development of promising biomarkers for screening, diagnosis, treatment, and prognosis. Here, we used quantitative liquid chromatography‐tandem mass spectrometry (LC–MS/MS) to identify differentially expressed proteins (DEPs) in plasma collected from patients with AIDS‐NHL and human immunodeficiency virus (HIV)‐infected patients without NHL (HIV+). Proteins with a log2 (fold change) in abundance >0.26 and p < 0.05 were considered differentially abundant. In total, 84 DEPs were identified, among which 20 were further validated as potential biomarkers, with immunoglobulin and complement components being the most common proteins. Some of the proteins were further verified in a retrospective analysis of the medical records of patients in a larger cohort. These markedly altered proteins were found to mediate pathophysiological pathways that likely contribute to AIDS‐NHL pathogenesis, such as the humoral immune response, complement activation, and complement and coagulation cascades. Our findings provide a new molecular understanding of AIDS‐NHL pathogenesis and provide new evidence supporting the identification of these proteins as possible biomarkers in AIDS‐NHL.

Plasma proteomic analysis reveals altered protein abundances in HIV‐infected patients with or without non‐Hodgkin lymphoma

Advanced studies have shown a biological correlation between hepatitis B virus (HBV) and B-cell lymphoma, especially diffuse large B-cell lymphoma (DLBCL). Patients with DLBCL infected with HBV (HBV-associated DLBCL) are clinically characterized by an advanced clinical stage, poor response to front-line immunochemotherapy regimens, and worse clinical prognosis. HBV-associated DLBCL often exhibits abnormal activation of the nuclear factor kappa B pathway as well as mutations in oncogenes, including Myc and BCL-6. Currently, there is no consensus on any specific and effective treatment for HBV-associated DLBCL. Therefore, in this review, we comprehensively and mechanistically analyzed the natural history of HBV infection and immunity, including HBV-mediated oncogenes, immune escape, epigenetic alterations, dysregulated signaling pathways, and potential therapeutic approaches for HBV-associated DLBCL. We hope that an improved understanding of the biology of HBV-associated DLBCL would lead to the development of novel therapeutic approaches, enhance the number of effective clinical trials, and improve the prognosis of this disease.

/pdf/hbv-associated-dlbcl-of-poor-prognosis-advance-in-3to6hlxz.pdf

HBV-associated DLBCL of poor prognosis: advance in pathogenesis, immunity and therapy

The development of lymphoma is a complex multistep process that integrates numerous experimental findings and clinical data that have not yet yielded a definitive explanation. Studies of oncogenic viruses can help to deepen insight into the pathogenesis of lymphoma, and identifying associations between lymphoma and viruses that are established and unidentified should lead to cellular and pharmacologically targeted antiviral strategies for treating malignant lymphoma. This review focuses on the pathogenesis of lymphomas associated with hepatitis B and C, Epstein-Barr, and human immunodeficiency viruses as well as Kaposi sarcoma-associated herpesvirus to clarify the current status of basic information and recent advances in the development of virus-associated lymphomas.

Carcinogenic mechanisms of virus-associated lymphoma

Hepatitis B virus reactivation: overview and management

Comprehensive profiling of actionable mutations in non-small cell lung cancer (NSCLC) is vital to guide targeted therapy, thereby improving the survival rate of patients. Despite the high incidence and mortality rate of NSCLC in Vietnam, the actionable mutation profiles of Vietnamese patients have not been thoroughly examined. Here, we employed massively parallel sequencing to identify alterations in major driver genes (EGFR, KRAS, NRAS, BRAF, ALK and ROS1) in 350 Vietnamese NSCLC patients. We showed that the Vietnamese NSCLC patients exhibited mutations most frequently in EGFR (35.4%) and KRAS (22.6%), followed by ALK (6.6%), ROS1 (3.1%), BRAF (2.3%) and NRAS (0.6%). Interestingly, the cohort of Vietnamese patients with advanced adenocarcinoma had higher prevalence of EGFR mutations than the Caucasian MSK-IMPACT cohort. Compared to the East Asian cohort, it had lower EGFR but higher KRAS mutation prevalence. We found that KRAS mutations were more commonly detected in male patients while EGFR mutations was more frequently found in female. Moreover, younger patients (<61 years) had higher genetic rearrangements in ALK or ROS1. In conclusions, our study revealed mutation profiles of 6 driver genes in the largest cohort of NSCLC patients in Vietnam to date, highlighting significant differences in mutation prevalence to other cohorts.

/pdf/actionable-mutation-profiles-of-non-small-cell-lung-cancer-21viy8vllv.pdf

Actionable Mutation Profiles of Non-Small Cell Lung Cancer patients from Vietnamese population.

Emerging evidences indicate that hepatitis B virus (HBV) infection is associated with non-Hodgkin lymphoma (NHL), but the mechanisms of HBV-induction lymphomagenesis remain unclear. In this report, retrospective analysis of the prevalence of hepatitis B surface antigen (HBsAg) among NHL cases demonstrated significantly higher HBsAg carrier rate among B-cell NHL cases than controls (other cancers except primary liver cancer) (adjusted odds ratio, 1.56; 95% confidence interval, 1.13-2.16). Furthermore, cells with an immortalization potential existed in the peripheral blood of 4 patients with chronic HBV infection. Characterization of these cells showed their immunophenotypes similar to that of the majority of HBsAg-positive B-cell NHL patients. Immunoglobulin (Ig) gene rearrangements confirmed the clonal Ig gene rearrangements. Cytogenetic analysis revealed abnormal karyotypes of these cells with an immortalization potential. Compared with cells with an immortalization potential that we previously found in B-cell NHL patients by the same way, these cells showed many similar features. In conclusion, cells with an immortalization potential existed in the part of patients with chronic HBV infection before lymphoma development and showed some malignant features. They may be the cellular basis of HBV-associated lymphomagenesis.

Establishment and characterization of HBV-associated B lymphocytes with an immortalization potential

Isolation of viable circulating tumor cells (CTC) holds the promise for improving screening, early diagnosis, and personalized treatment of lymphoma. In this study, we isolated and characterized spontaneously immortalized B-lymphocyte (SIBC) lines from HIV-infected patients with and without Non-Hodgkin's Lymphoma (AIDS-NHL). A total of 22 SIBC lines was isolated from peripheral blood mononuclear cells (PBMC) of HIV-infected patients with (n = 40) and without (n = 77) clinically detectable NHL, but not from healthy individuals (n = 34). Of these, 8 SIBC lines named HIV-SIBC were generated from HIV-infected patients without AIDS-NHL (10%, 8/77), while 14 SIBCs named AIDS-NHL-SIBC were from 13 of the AIDS-NHL patients (32.5%, 13/40). Among the 14 AIDS-NHL-SIBCs, 12 were derived from AIDS-NHL patients with poor prognoses (survival time less than 1 year). SIBCs displayed markers typical of memory B cells (CD3- CD20+ CD27+ ) with EBV infection. Moreover, AIDS-NHL-SIBCs were representative of CTC as evidenced by monoclonal Ig gene rearrangement, abnormal chromosomal karyotype, and the formation of xenograft tumors, while HIV-SIBCs generated harbored some features of tumor cells, none had the capacity of xenograft tumor formation, suggesting HIV-SIBC present the precursor of CTC. These results indicate that SIBCs is associated with poor prognosis in AIDS-NHL patients and can be isolated from HIV-infected patients with NHL and without NHL. This findings point to the need for further molecular characterization and functional studies of SIBCs, which may prove the value of SIBCs in the diagnosis, prognoses, and screening for NHL among HIV-infected patients.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/cam4.2508

Isolation and characterization of spontaneously immortalized B-lymphocyte lines from HIV-infected patients with and without non-Hodgkin's Lymphoma.

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Establishment and characterization of HBV-associated B lymphocytes with an immortalization potential

Isolation and characterization of spontaneously immortalized B-lymphocyte lines from HIV-infected patients with and without non-Hodgkin's Lymphoma.