ABSTRACT
BACKGROUND: Prognostic genes in the tumor microenvironment play an important role in immune biological processes and the response of cancer to immunotherapy. Thus, we aimed to assess new biomarkers that are associated with immune/stromal cells in lung adenocarcinomas (LUAD) using the ESTIMATE algorithm, which also significantly affects the prognosis of cancer. METHODS: The RNA sequencing (RNA-Seq) and clinical data of LUAD were downloaded from the the Cancer Genome Atlas (TCGA ). The immune and stromal scores were calculated for each sample using the ESTIMATE algorithm. The LUAD gene chip expression profile data and the clinical data (GSE37745, GSE11969, and GSE50081) were downloaded from the Gene Expression Omnibus (GEO) for subsequent validation analysis. Differentially expressed genes were calculated between high and low score groups. Univariate Cox regression analysis was performed on differentially expressed genes (DEGs) between the two groups to obtain initial prognosis genes. These were verified by three independent LUAD cohorts from the GEO database. Multivariate Cox regression was used to identify overall survival-related DEGs. UALCAN and the Human Protein Atlas were used to analyze the mRNA /protein expression levels of the target genes. Immune cell infiltration was evaluated using the Tumor Immune Estimation Resource (TIMER) and CIBERSORT methods, and stromal cell infiltration was assessed using xCell. RESULTS: In this study, immune scores and stromal scores are significantly associated with the clinical characteristics of LUAD, including T stage, M stage, pathological stage, and overall survival time. 530 DEGs (18 upregulated and 512 downregulated) were found to coexist in the difference analysis with the immune scores and stromal scores subgroup. Univariate Cox regression analysis showed that 286 of the 530 DEGs were survival-related genes (p < 0.05). Of the 286 genes initially identified, nine prognosis-related genes (CSF2RB, ITK, FLT3, CD79A, CCR4, CCR6, DOK2, AMPD1, and IGJ) were validated from three separate LUAD cohorts. In addition, functional analysis of DEGs also showed that various immunoregulatory molecular pathways, including regulation of immune response and the chemokine signaling pathways, were involved. Five genes (CCR6, ITK, CCR4, DOK2, and AMPD1) were identified as independent prognostic indicators of LUAD in specific data sets. The relationship between the expression levels of these genes and immune genes was assessed. We found that CCR6 mRNA and protein expression levels of LUAD were greater than in normal tissues. We evaluated the infiltration of immune cells and stromal cells in groups with high and low levels of expression of CCR6 in the TCGA LUAD cohort. In summary, we found a series of prognosis-related genes that were associated with the LUAD tumor microenvironment.
ABSTRACT
OBJECTIVE: To investigate clinical features of the patients with hepatitis B superinfected with acute hepatitis E (AHE). METHODS: Totally 625 consecutive patients enrolled from Dec 2002 to Dec 2006 were studied retrospectively. All of the patients were subclassified into acute hepatitis E group (AHE=437 cases) and Superinfected Group (S=188 cases), and S group was further divided into the group of chronic hepatitis B superinfected with acute hepatitis E (CHB+AHE, 130 cases) and the group of liver cirrhosis and hepatitis B superinfected with acute hepatitis E (LCB+AHE, 58 cases). In 32 of the 188 superinfected patients the effects of HEV on HBV were observed by comparing the levels of HBV DNA in acute vs. convalescence stages. RESULTS: Compared with the patients with AHE, the superinfected patients had a higher level of total bilirubin (TBil), an elevated frequency of fulminate hepatitis, mortality and a longer period of the mean hospital stay for the cured patients but significantly lower levels of alanine aminotransferase (ALT), serum albumin and prothrombin activity (PA). Furthermore, the group of LCB+AHE had a higher level of TBil and higher incidences of complications such as ascites, peritonitis, hepatic encephalopathy and disturbance in glycometabolism than the group of CHB+AHE. The follow-up for the superinfected patients showed that 20 of 32 patients (62.5 percent) had decreased copies of HBV DNA during the recovery phase compared with the acute phase, and the mean decrease of HBV DNA was 2.1 log10. The HBV DNA was in a persistently undetectable level in 6 of 32 (18.8 percent) superinfected patients. However, 4 of 32 patients (12.5 percent) showed an unchanged levels of HBV DNA and 2 cases (6.2 percent) had a slightly increased HBV DNA levels. CONCLUSION: Superinfection with AHE in patients with chronic hepatitis B leads to a more severe hepatic damage and the replication of HBV DNA can be transiently inhibited.
