Host susceptibility to severe influenza A virus infection.

Most people exposed to a new flu virus do not notice any symptoms. A small minority develops critical illness. Some of this extremely broad variation in susceptibility is explained by the size of the initial inoculum or the influenza exposure history of the individual; some is explained by generic host factors, such as frailty, that decrease resilience following any systemic insult. Some demographic factors (pregnancy, obesity, and advanced age) appear to confer a more specific susceptibility to severe illness following infection with influenza viruses. As with other infectious diseases, a substantial component of susceptibility is determined by host genetics. Several genetic susceptibility variants have now been reported with varying levels of evidence. Susceptible hosts may have impaired intracellular controls of viral replication (e.g. IFITM3, TMPRS22 variants), defective interferon responses (e.g. GLDC, IRF7/9 variants), or defects in cell-mediated immunity with increased baseline levels of systemic inflammation (obesity, pregnancy, advanced age). These mechanisms may explain the prolonged viral replication reported in critically ill patients with influenza: patients with life-threatening disease are, by definition, abnormal hosts. Understanding these molecular mechanisms of susceptibility may in the future enable the design of host-directed therapies to promote resilience.

Identification of biomarkers for pseudo and true progression of GBM based on radiogenomics study.

The diagnosis for pseudoprogression (PsP) and true tumor progression (TTP) of GBM is a challenging task in clinical practices. The purpose of this study is to identify potential genetic biomarkers associated with PsP and TTP based on the clinical records, longitudinal imaging features, and genomics data. We are the first to introduce the radiogenomics approach to identify candidate genes for PsP and TTP of GBM. Specifically, a novel longitudinal sparse regression model was developed to construct the relationship between gene expression and imaging features. The imaging features were extracted from tumors along the longitudinal MRI and provided diagnostic information of PsP and TTP. The 33 candidate genes were selected based on their association with the imaging features, reflecting their relation with the development of PsP and TTP. We then conducted biological relevance analysis for 33 candidate genes to identify the potential biomarkers, i.e., Interferon regulatory factor (IRF9) and X-ray repair cross-complementing gene (XRCC1), which were involved in the cancer suppression and prevention, respectively. The IRF9 and XRCC1 were further independently validated in the TCGA data. Our results provided the first substantial evidence that IRF9 and XRCC1 can serve as the potential biomarkers for the development of PsP and TTP.

P48 is a predictive marker for outcome of postoperative interferon-alpha treatment in patients with hepatitis B virus infection-related hepatocellular carcinoma.

BACKGROUND: Postoperative interferon-alpha (IFN-alpha) therapy improved survival in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). The identification of predictive markers of outcome will help to select patients who are most likely to benefit from treatment. METHODS: An immunohistochemical study of P48 was performed on specimens that were collected from patients in a randomized trial who received postoperative IFN-alpha therapy (Group 1; n = 80 patients) and who did not receive postoperative IFN-alpha therapy (Group 2; n = 75 patients). Positive P48 expression was graded as >/=20% positive cells in 1 sample. RESULTS: Eighty-one patients were positive for P48, and 74 patients were negative for P48. The clinicopathologic data were comparable between patients with P48-negative and P48-positive staining. Disease-free survival (DFS) and overall survival (OS) in P48-positive patients were better than that in P48-negative patients in Group 1 (DFS, P = .036; OS, P = .014), however, DFS and OS did not differ between patients with positive and negative P48 in Group 2. OS in P48-positive patients from Group 1 was better than that in patients with P48-positive patients from Group 2 (OS, P = .001) but did not differ when P48 was negative. In Group 1, the risk factors for DFS were cirrhosis and P48 staining, and the risk factors for OS were tumor differentiation and P48 staining. Receiver operating curve analysis indicated that, in the first 2 years of DFS, combined cirrhosis and P48 had good predictive accuracy; and, in the first 4 years of OS, combined tumor differentiation and P48 had good predictive accuracy. CONCLUSIONS: P48 was useful as a predictive marker of outcome after postoperative IFN-alpha treatment in patients with HBV-related HCC.