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Background: Prognostic biomarkers remain a focus in colorectal cancer during last decades. There are some studies of E2F transcription factors in different cancer. But the utility of E2F transcription factors as cancer biomarkers in colorectal cancer has not been confirmed. In this research we analyzed multiple databases and performed experimental validation of E2Fs as biomarkers. Methords: Bioinformatics analysis was the main part of this research. Besides, IHC was used to the huamn normal and tumor tissues.Results: Our study showed that the mRNA expression levels of E2F1/3/4/5/6/7/8 were significantly upregulated in carcinoma tissues, whereas E2F2 mRNA was downregulated. High E2F3/4 expression correlated with poor prognosis, whereas high E2F2 expression was correlated with good prognosis. Pathological parameters indicated that expression levels of E2F1/3/5 varied in different tumor stages; however, expression of E2F2/4/6/7/8 did not vary with tumor stage. E2F4 expression was higher in men than women. For pathological type, E2F8 expression was higher in the mucinous adenocarcinoma group compared with the adenocarcinoma group. E2F expression levels were altered in 175 of 524 patients (33%) with colorectal cancer, and the alterations of E2Fs in mucinous adenocarcinoma were more frequent than in adenocarcinoma. Cell cycle was the core function and the most enriched pathway of E2Fs. The functions of E2F2/3/4 may be regulated by some miRNAs. Conclusions: We proved that E2F2/3/4 can be used as prognostic biomarkers for colorectal cancer, and E2F2/3/4 mRNAs may be targeted by some miRNAs to influence “CELL CYCLE” pathway and exert their core functions in colorectal cancer.

Background Primary bilateral macronodular adrenocortical hyperplasia (PBMAH) is a rare form of adrenal Cushing’s syndrome. The slowly progressing expansion of bilateral adrenal tissues usually persists for dozens of years, leading to delayed onset with severe conditions due to chronic mild hypercortisolism. About 20–50% cases were found to be caused by inactivating mutation of armadillo repeat-containing protein 5 (ARMC5) gene. Case presentation A 51-year-old man was admitted for severe diabetes mellitus, resistant hypertension, centripedal obesity and edema. PBMAH was diagnosed after determination of adrenocorticotropic hormone and cortisol levels, dexamethasone suppression tests and abdominal contrast-enhanced CT scanning. The metabolic disorders of the patient remarkably improved after sequentially bilateral laparoscopic adrenalectomy combined with hormone replacement. Sanger sequencing showed germline nonsense mutation of ARMC5 c.967C>T (p.Gln323Ter). The second somatic missense mutation of ARMC5 was detected in one out of two resected nodules, reflecting the second-hit model of tumorigenesis. Routine genetic testing in his apparently healthy offspring showed one of two daughters and one son harbored the germline mutation. Conclusions In conclusion, our case report highlight the importance of genetic testing in the molecular diagnosis of PBMAH. Genetic screening in related family members will find out asymptomatic variant carriers to guide life-long follow-up.

Background: Rs31489 in the cleft lip and palate transmembrane1-like gene (CLPTM1L) has been identified to be associated with lung cancer through genome-wide association studies (GWAS). However, some recent replication studies yielded inconclusive results. Thus, we undertook this study to investigate the precise effect of rs31489 on lung cancer susceptibility. Materials and Methods: A hospital-based case-control study in 1,673 Chinese subjects (611 individuals with lung cancer and 1,062 controls) and a meta-analysis among 32,199 subjects (16,364 cases and 15,835 controls) were performed in this study. Results: In our case-control study, rs31489 was inversely associated with lung cancer (AC versus CC: OR=0.68, 95%CI=0.52-0.88; additive model: OR=0.68, 95%CI=0.54-0.85; dominant model: OR=0.65, 95%CI =0.51-0.84). Stratification analysis by smoking status showed a significant association and strong genetic effect in non-smokers but not in smokers. Our metaanalysis further confirmed the association, although with significant heterogeneity contributed by study design and source of controls, as shown by stratified analysis. Sensitive and cumulative analyses both indicated robust stability of our results. In addition, there was no observable publication bias in our meta-analysis. Conclusions: Overall, the findings from our replication study and meta-analysis demonstrated that CLPTM1L gene rs31489 is significantly associated with lung cancer.

The effects of Bone morphogenetic protein 2 (BMP-2) on the angiogenesis of hepatocellular carcinoma have not yet been observed and its molecular mechanisms is not clear. We first constructed the recombinant lentivirus vectors expressing small hairpin RNA against BMP-2 gene (LV-SH-BMP2) and the recombinant lentivirus vectors over-expressing BMP-2 (overexpression-LV-BMP2), and then the two recombinant lentivirus vectors were respectively transfected into Hep G2 cells. The Hep G2 cells transfected with LV-SH-BMP2 or overexpression-LV-BMP2 were respectively co-cultured with human umbilical vein endothelial cells (HUVECs) to observe the effects of BMP-2 on HUVECs. The effect of BMP-2 on tumor microvessel density (MVD) was examined. The abilities of proliferation, migration and angiogenesis were significantly inhibited in the HUVECs co-cultured with BMP-2 knockdown Hep G2 (all P P P

p53 is a key regulator in cell apoptosis, and cancer cells deficient in p53 expression fail to respond to chemotherapy. Here we show that effective Doxorubicin (DOX)-induced apoptosis is p53-dependent. However, an alternative treatment of DOX/TNF-alpha/DOX restored sensitivity of p53-deficient cells to DOX-induced apoptosis. Treatment of cells with TNF-alpha resulted in a decrease of p21 (waf1/cip1/sdi1) expression following second dose of DOX. In previous work, we demonstrated that p21 suppressed DOX-induced apoptosis via its (cyclin-dependent kinase) CDK-binding and CDK-inhibitory activity. Thus, we propose that TNF-alpha enhances the anti-cancer effect of DOX through suppressing the anti-apoptotic activity of p21, and that a combined treatment TNF-alpha/Dox is an effective chemotherapeutic strategy for p53-deficient cancers.