Decreased Th1/Th2 ratio is one of the major characteristics of immunosuppression in sepsis. Both membrane adhesive protein Annexin-A1 (ANXA1) and transcription factor GATA-3 have been reported to play important roles in T cell differentiation. However, the relationship between ANXA1 and GATA-3 in Th1/Th2 shift is unknown. Our study investigated the interaction effects of ANXA1 and GATA-3 to influence T cell differentiation in CD4+ T cells. We found that GATA-3 and ANXA1 were coexpressed on Th0/Th1/Th2 cytoplasm and nuclear. Overexpressed ANXA1 significantly increased the expression of IFNγ and reduced IL-4 expression in T cells, while ANXA1-silenced T cells exhibited decreased production of IFNγ and increased production of IL-4. Knockdown of ANXA1 promoted higher expression level of GATA-3 and low level of T-box transcription factor (T-bet/Tbx21). Further study demonstrated that ANXA1 regulated GATA-3 expression through the formyl peptide receptor like-1 (FPRL-1) downstream signaling pathways ERK and PKB/Akt. These results suggested that ANXA1 modulates GATA-3/T-bet expression induced Th0/Th1 differentiation. Moreover, we found that GATA-3 inhibited ANXA1 expression by binding to its promoter for the first time. It is proposed that the interactions between ANXA1 and GATA-3 may provide clues to understand the immunosuppression and have potential as new therapeutic targets in immunotherapy after sepsis.

The differential protein peaks analysed by SELDI-TOF-MS may contain promising serum biomarkers for screening ESCC. The diagnostic model which combined only six protein peaks had a satisfactory discriminatory power. The model should be further evaluated in other populations of ESCC patients and tested against controls. The nature and function of the discriminating proteins have yet to be elucidated.

Identifying patients at high risk of metastasis is a major challenge in lung adenocarcinoma (ADC) therapy, therefore discovery of noninvasive biomarkers and therapeutic targets is urgent. We found significant differences between the secretomes of differentially expressed proteins in lung ADC cell lines, clinical tissue samples and serum plasma samples with high and low metastatic potential. In particular, Apolipoprotein E (APOE) levels were three-times greater in cells with lymph node metastases (LNM) than those without. Our study indicates that APOE is a potential indicator of metastatic lung ADC and that secretomes may offer a valuable resource for biomarkers of lung ADC with LNM.

The prognostic role of phosphatase and tensin homolog (PTEN) in non-small cell lung cancer (NSCLC) has been controversial. In this study, levels of PTEN expression were investigated in NSCLC patients and their prognostic value in NSCLC was assessed. PTEN expression in tumor tissues from 68 NSCLC patients was analyzed using immunohistochemistry and confocal microscopy. Survival analysis was performed using the log-rank test and Cox proportional hazards regression analysis. NSCLC patients classified as expressers of high levels of PTEN (n = 46) had better prognoses than those classified as expressers of low levels (mean survival 17.1 vs. 12.9 months, log rank P = 0.038). In patients with adenocarcinoma (AC), high PTEN expression (n = 9) was associated with significantly longer survival than low PTEN expression (mean survival 23.50 vs. 15.54 months, log rank P = 0.043). High levels of PTEN expression resulted in 43 % reduction in risk for all NSCLC patients (HR 0.57, 95 % CI 0.33-0.98, P = 0.041). PTEN expression and clinical stage remained significantly associated with survival after adjustment for age, sex, and tumor type (HR 0.56, 95 % CI 0.32-0.99; P = 0.048; HR 0.54, 95 % CI 0.36-0.97; P = 0.045). No significant difference in continuous PTEN expression levels was observed among groups with different clinical or pathological characteristics (P > 0.17). When levels of PTEN expression were binarized using the optimal cut-point, higher levels of PTEN expression were observed in patients with T1/T2 than in those with T3/T4 (80 and 58 %, respectively, P = 0.049) and in patients with AC than in those with squamous-cell carcinoma (78 and 58 %, respectively, P = 0.08). No significant difference in binarized PTEN expression levels was found among groups with any other clinical/pathologic characteristic (P > 0.28). Our results suggest that high levels of PTEN expression may be favorable prognostic markers in NSCLC patients.