Rabbit Anti-Human ABL2 (N-terminal) Polyclonal antibody

Background Methods We previously identified a blood RNA transcript-based model consisting of six immune or inflammatory response genes (ABL2, SEMA4D, ITGAL, C1QA, TIMP1, and CDKN1A) that was prognostic for survival in cohorts of men with castration-resistant prostate cancer (CRPC). We investigated whether inherited variation in these six genes was associated with overall survival (OS) in men with CRPC. The test cohort comprised 600 patients diagnosed with CRPC between 1996 and 2011 at Dana-Farber Cancer Institute. Genotyping of 66 tagging single nucleotide polymorphisms (SNPs) spanning the six genes was performed on blood derived DNAs. For the top four SNPs (P < 0.05), validation was conducted in an independent cohort of 223 men diagnosed with CRPC between 2000 and 2014. Multivariable Cox regression adjusting for known prognostic factors estimated hazard ratios (HR) and 95% confidence intervals (CI) of the association of genetic variants with OS. Results Conclusions Two thirds of patients in both cohorts had metastases at CRPC diagnosis. Median OS from CRPC diagnosis was 3.6 (95%CI 3.3-4.0) years in the test cohort and 4.6 (95%CI 3.8-5.2) years in the validation cohort. Fifty-nine SNPs in Hardy-Weinberg equilibrium were analyzed. The major alleles of rs1318056 and rs1490311 in ABL2, and the minor alleles of rs2073917 and rs3764322 in ITGAL were associated with increased risk of death in the test cohort (adjusted-HRs 1.27-1.39; adjusted-p <0.05; false discovery rate <0.35). In the validation cohort, a similar association with OS was observed for rs1318056 in ABL2 (adjusted-HR 1.44; 95%CI 0.89-2.34) and rs2073917 in ITGAL (adjusted-HR 1.41; 95%CI 0.82-2.42). The associations did not reach statistical significance most likely due to the small sample size of the validation cohort (adjusted-p = 0.142 and 0.209, respectively). Additional eQTL analysis indicated that minor alleles of rs1318056 and rs1490311 in ABL2 are associated with a lower ABL2 expression in blood. These findings corroborate our initial work on the RNA expression of genes involved in immunity and inflammation from blood and clinical outcome and suggest that germline polymorphisms in ABL2 and ITGAL may be associated with the risk of death in men with CRPC. Further studies are needed to validate these findings and to explore their functional mechanisms.

Although micro RNA (miRNA) expression profiles are widely investigated in renal cell carcinoma (RCC), their potential roles for affecting RCC initiation and progression remain largely unknown. Here, we examined the aberrant expression profiles of miRNAs inhuman metastatic RCC tissues based on Gene Expression Omnibus (GSE37989). We further validated them iRNAs expression data in the largest clinical dataset: The Cancer Genome Atlas (TCGA). And cell adhesion and migration abilities and epithelial me senchymal transition (EMT) related proteins were assessed in both normal and tumor RCC cell lines. We suggest that hsa-miR-143 is a potential tumor suppressor in RCC as its down regulation positively correlated with adverse prognosis. Biologically, cell adhesion, migration, and EMT were dramatically inhibited by miR-143. Mechanistically, we found that miR-143 targets ABL proto-oncogene 2 (ABL2), which was also found to be an indicator for poor survival in TCGA database. Our results have important implications in understanding functions of miRNAs in metastatic RCC and will provide a basis for further clinical application.