TRIAP1 knockdown sensitizes non-small cell lung cancer to ionizing radiation by disrupting redox homeostasis.

BACKGROUND: Radioresistance of some non-small cell lung cancer (NSCLC) types increases the risk of recurrence or metastasis in afflicted patients, following radiotherapy. As such, further improvements to NSCLC radiotherapy are needed. The expression of oncogene TP53-regulated inhibitor of apoptosis 1 (TRIAP1) in NSCLC is increased following irradiation. Furthermore, gene set enrichment analysis (GSEA) has suggested that TRIAP1 might be involved in maintaining redox homeostasis. This in turn might enhance cell radioresistance. METHODS: In this study we irradiated human NSCLC cell lines (A549 and H460), while knocking down TRIAP1, to determine whether a disrupted redox homeostasis could attenuate radioresistance. RESULTS: Irradiation notably increased both mRNA and protein levels of TRIAP1. In addition, TRIAP1 knockdown decreased the expression of several antioxidant proteins, including thioredoxin-related transmembrane protein (TMX) 1, TMX2, thioredoxin (TXN), glutaredoxin (GLRX) 2, GLRX3, peroxiredoxin (PRDX) 3, PRDX4, and PRDX6 in A549 and H460 cells. In addition, silencing TRIAP1 impaired the radiation-induced increase of the aforementioned proteins. Continuing along this line, we observed a radiation-induced reduction of cell viability and invasion, as well as increased apoptosis and intracellular reactive oxygen species following TRIAP1 knockdown. CONCLUSIONS: In summary, we identified TRIAP1 as a key contributor to the radioresistance of NSCLC by maintaining redox homeostasis.

Prognostic significance of HOXD13 expression in human breast cancer.

Homeobox protein Hox-D13 has been recognized as a tumor suppressor in pancreatic cancer. To evaluate the function of HOXD13 in invasive breast cancer pathogenesis, we examined HOXD13 expression in 434 breast cancer tissues and 230 their counterpart normal breast tissues by immunohistochemistry using a tissue microarray (TMA). The association between HOXD13 expression and clinicopathological factors was analyzed by use of Chi-square test. Kaplan-Meier survival curves and log-rank tests were applied to analyze the survival status. Cox regression was applied for multivariate analysis of prognosis. We found that low HOXD13 expression accounts for 84.3% in breast cancer tissues. Low HOXD13 expression was significantly associated with large tumor size (P=0.038) and positive lymph node metastasis (LNM) (P=0.026). In Kaplan-Meier survival curves and log-rank tests, the patients with HOXD13-negative breast cancer showed significantly poorer outcomes (69.867 ± 1.058 months) in terms of overall survival (OS) than positive-HOXD13-expression patients (76.248 ± 1.069 months) (P=0.003). And in multivariate analysis, low level of HOXD13 expression was a significant unfavorable prognostic factor. So we conclude that down-regulation of HOXD13 might be a potentially useful prognostic marker for patients with breast cancer.

Long CAG repeat sequence and protein expression of androgen receptor considered as prognostic indicators in male breast carcinoma.

BACKGROUND: The androgen receptor (AR) expression and the CAG repeat length within the AR gene appear to be involved in the carcinogenesis of male breast carcinoma (MBC). Although phenotypic differences have been observed between MBC and normal control group in AR gene, there is lack of correlation analysis between AR expression and CAG repeat length in MBC. The purpose of the study was to investigate the prognostic value of CAG repeat lengths and AR protein expression. METHODS: 81 tumor tissues were used for immunostaining for AR expression and CAG repeat length determination and 80 normal controls were analyzed with CAG repeat length in AR gene. The CAG repeat length and AR expression were analyzed in relation to clinicopathological factors and prognostic indicators. RESULTS: AR gene in many MBCs has long CAG repeat sequence compared with that in control group (P = 0.001) and controls are more likely to exhibit short CAG repeat sequence than MBCs. There was statistically significant difference in long CAG repeat sequence between AR status for MBC patients (P = 0.004). The presence of long CAG repeat sequence and AR-positive expression were associated with shorter survival of MBC patients (CAG repeat: P = 0.050 for 5y-OS; P = 0.035 for 5y-DFS AR status: P = 0.048 for 5y-OS; P = 0.029 for 5y-DFS, respectively). CONCLUSION: The CAG repeat length within the AR gene might be one useful molecular biomarker to identify males at increased risk of breast cancer development. The presence of long CAG repeat sequence and AR protein expression were in relation to survival of MBC patients. The CAG repeat length and AR expression were two independent prognostic indicators in MBC patients.