The correlation of fibrinogen-like protein-1 expression with the progression and prognosis of hepatocellular carcinoma.

BACKGROUND: Fibrinogen-like-protein 1 (FGL1), a member of the fibrinogen-related protein (FREP) family, is a major ligand of the immune inhibitory receptor lymphocyte-activation gene 3 (LAG-3). While FGL1 is strongly implicated in the development and prognosis of a variety of diseases, its role in hepatocellular carcinoma (HCC) is still disputed. Therefore, the role of FGL1 expression in the progression and prognosis of HCC was investigated. METHODS AND RESULTS: In the present study, bioinformatics analysis was first used to probe the expression profile of FGL1 in multiple malignant tumor tissues and paired normal tissues, and to explore the possible relationship between FGL1 and prognosis of HCC patients. Thereafter, the expression levels of FGL1 were determined and compared in human HCC cell lines, HCC tissues, peri-tumor tissues and normal liver tissues by western blot analysis. Furthermore, tissue microarrays were used to detect the expression of FGL1 through immunohistochemical staining and to verify whether the FGL1 expression level was associated with clinicopathological features and the prognosis of HCC patients. The results showed that FGL1 was downregulated significantly in most of the HCC cells lines and HCC tissues, corresponding to the results of the bioinformatics and western blot analyses. FGL1 expression level in HCC was found to be correlated to Edmondson grade and metastasis of the HCC. Additionally, high FGL1 expression was associated with better overall survival in HCC patients, suggesting that FGL1 could function as a tumor suppressor. CONCLUSIONS: The expression level of FGL1 can be correlated with the progression and prognosis of HCC, suggesting its potential as a prognostic biomarker.

Significance of Common Blood Test Indexes in the Diagnosis and Prognosis of Multiple Myeloma.

BACKGROUND: The goal of this study is to explore the clinical value of routine tests in multiple myeloma (MM). METHODS: A total of 179 MM patients, newly diagnosed in our hospital from January 2010 to December 2018 (case group), as well as 352 cases of healthy individuals (control group) were evaluated. Albumin (Alb), globulin (Glb), albumin/globulin (A/G), creatinine (Cr), calcium (Ca), hemoglobin (Hb), lactate dehydrogenase (LDH), platelet count (Plt), and platelet distribution width (PDW) were compared between the analyzed groups. Respective tests were screened by forward selection. Thereafter, screened out indicators were identified through logistic regression analysis. Risk prediction nomogram, area under curve (AUC), calibration, decision curve analysis (DCA), and clinical impact curve (CIC) were further performed. At the same time, routine test indicators of MM patients for stage and subtype diagnosis, were compared. A correlation analysis between these test indicators and respective disease stages was performed. High stage group and low stage groups were subsequently compared to define the predictive value of single and combined indicators of disease severity. RESULTS: Except for Ca, the difference between the case and control groups for all other blood indicators was statistically significant (p < 0.05). Moreover, the difference in positive rate(s) was statistically significant (p < 0.05). The receiver operating characteristic (ROC) curve of Alb, Hb, and PDW harbored robust discrimination (AUC = 0.960) and appropriate calibration. The DCA and CIC showed that the resulting nomogram had a superior net benefit in predicting MM. Among all indicators, only LDH was statistically reduced in MM patients at ISS stages I, II, and III (p < 0.05). Interestingly, the ISS stage of respective MM patients was positively correlated with Cr (τ = 0.392), while it was negatively correlated with Hb (τ = -0.364). Alb, Glo, A/G, and Hb were significantly distinct between heavy chain (IgG, IgA) and LC, while few significant differences were found between the ISS stages. Lastly, the AUC (0.828) for Cr was greater than that for all other single and combined indicators. CONCLUSIONS: The effective application of major indicators measured in routine blood tests can provide important clues for the diagnosis and prognosis of MM.

Current Progress in Investigating Mature T- and NK-Cell Lymphoma Gene Aberrations by Next-Generation Sequencing (NGS).

Despite efforts to abrogate the severe threat to life posed by the profound malignancy of mature natural killer/T-cell lymphoma (NKTCL), therapeutic advances still require further investigation of its inherent regulatory biochemical processes. Next-generation sequencing (NGS) is an increasingly developing gene detection technique, which has been widely used in lymphoma genetic research in recent years. Targeted therapy based on the above studies has also generated a series of advances, making genetic mutation a new research hotspot in lymphoma. Advances in NKTCL-related gene mutations are reviewed in this paper.

Oncolytic viruses as a promising therapeutic strategy for hematological malignancies.

The incidence of hematological malignancies such as multiple myeloma, leukemia, and lymphoma has increased over time. Although bone marrow transplantation, immunotherapy and chemotherapy have led to significant improvements in efficacy, poor prognosis in elderly patients, recurrence and high mortality among hematological malignancies remain major challenges, and innovative therapeutic strategies should be explored. Besides directly lyse tumor cells, oncolytic viruses can activate immune responses or be engineered to express therapeutic factors to increase antitumor efficacy, and have gradually been recognized as an appealing approach for fighting cancers. An increasing number of studies have applied oncolytic viruses in hematological malignancies and made progress. In particular, strategies combining immunotherapy and oncolytic virotherapy are emerging. Various phase I clinical trials of oncolytic reovirus with lenalidomide or programmed death 1(PD-1) immune checkpoint inhibitors in multiple myeloma are ongoing. Moreover, preclinical studies of combinations with chimeric antigen receptor T (CAR-T) cells are underway. Thus, oncolytic virotherapy is expected to be a promising approach to cure hematological malignancies. This review summarizes progress in oncolytic virus research in hematological malignancies. After briefly reviewing the development and oncolytic mechanism of oncolytic viruses, we focus on delivery methods of oncolytic viruses, especially systemic delivery that is suitable for hematological tumors. We then discuss the main types of oncolytic viruses applied for hematological malignancies and related clinical trials. In addition, we present several ways to improve the antitumor efficacy of oncolytic viruses. Finally, we discuss current challenges and provide suggestions for future studies.