Recently, many studies have shown that pretreatment serum albumin can be closely linked to the prognosis of cancer patients, including those with renal cell carcinoma (RCC). However, not all studies have reached the same conclusion. We therefore conducted a systematic review and meta-analysis to evaluate the prognostic value of pretreatment serum albumin in RCC patients. A total of 17 studies involving 6,447 patients were included in our meta-analysis. Our results indicated that a lower pretreatment serum albumin level yielded a worse overall survival (hazard ratio [HR]=2.46, 95% confidence interval [CI] 1.92–3.13), cancer-specific survival (HR=2.22, 95% CI 1.87–2.64), and relapse-free survival/progression-free survival (HR=1.75, 95% CI 1.28–2.38). Generally, these findings were particularly pronounced when stratified by tumor type, analysis type, cut-off value, and HR-obtaining method. In conclusion, a decreased pretreatment serum albumin level implies a poor prognosis for RCC patients, and can be monitored for risk stratification and individualized treatment in RCC patients.

Genome-wide association studies (GWAS) have identified more than 2000 single nucleotide polymorphisms (SNPs) associated with breast cancer susceptibility, most of which are located in the non-coding region. However, the causal SNPs functioning as gene regulatory elements still remain largely undisclosed. Here, we applied a Dinucleotide Parallel Reporter sequencing (DiR-seq) assay to evaluate 288 breast cancer risk SNPs in nine different breast cancer cell lines. Further multi-omics analysis with the ATAC-seq (Assay for Transposase-Accessible Chromatin using sequencing), DNase-seq (DNase I hypersensitive sites sequencing) and histone modification ChIP-seq (Chromatin Immunoprecipitation sequencing) nominated seven functional SNPs in breast cancer cells. Functional investigations show that rs4808611 affects breast cancer progression by altering the gene expression of NR2F6. For the other site, rs2236007, the alteration promotes the binding of the suppressive transcription factor EGR1 and results in the downregulation of PAX9 expression. The downregulated expression of PAX9 causes cancer malignancies and is associated with the poor prognosis of breast cancer patients. Our findings contribute to defining the functional risk SNPs and the related genes for breast cancer risk prediction.

Objective. The phosphorylation status of the BCL2 Antagonist of Cell Death (BAD) protein influences cell survival and apoptosis. BAD phosphorylation is determined by the relative activity of a series of kinases and phosphatases within the BAD pathway. We therefore sought to evaluate the influence that expression of the BAD apoptosis pathway has on breast cancer progression and on clinical outcome in a series of breast cancer patients. Methods. We used Principal components analysis to derive a BAD-pathway gene expression signature with a corresponding “pathway score” representing overall gene expression levels for BAD pathway genes. The BAD-pathway signature score was evaluated in clinical-genomic breast cancer datasets obtained from a total of 502 patients, including intra-ductal hyperplasia (n=8), ductal carcinoma in-situ (n=30), and three separate data sets of invasive ductal carcinoma patient samples (n=23, n=286, n=155). The influence of the BAD-pathway signature score on breast cancer progression and relapse-free survival was evaluated by student's t-test and Kaplan Meier/log-rank test, respectively. Results. We developed a 48-gene BAD-pathway signature, the expression score of which decreased with progression from intra-ductal hyperplasia through ductal carcinoma in-situ and invasive ductal carcinoma (p=0.0004). Furthermore, BAD-pathway signature score was associated with relapse free survival from breast cancer in two independent clinical-genomic datasets (n=286, p=0.01; n=155, p=0.02). Conclusions.BAD pathway gene expression is associated with breast cancer progression and disease-free survival. The pathway represents an appealing human cancer prognostic biomarker and therapeutic target. Figures available in online version. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-08-01.