ABSTRACT
BACKGROUND: Prognosis associated with metastatic renal cell carcinoma (mRCC) can vary widely. METHODS: This study used pretreatment nephrectomy specimens from a randomized phase III trial. Expression levels of candidate genes were determined from archival tumors using the OpenArray® platform for TaqMan® RT-qPCR. The dataset was randomly divided at 2:1 ratio into training (n = 221) and testing (n = 103) sets to develop a multigene prognostic signature. FINDINGS: Gene expressions were measured in 324 patients. In the training set, multiple models testing 424 candidate genes identified a prognostic signature containing 8 genes plus MSKCC clinical risk factors. In the testing set, the time dependent (td) AUC for a prognostic model containing the 8 genes with and without MSKCC risk factors were 0.72 and 0.69, respectively. The tdAUC for the clinical risk factors alone was 0.61. Additional primary mRCCs from patients with mRCC (n = 12) were sampled in multiple sites and standard deviations of gene expressions within a tumor were used as a measure of heterogeneity. All 8 genes in the final prognostic model met our criteria for minimal heterogeneity. CONCLUSIONS: A molecular prognostic signature based on 8 genes was developed and is ready for external validation in this patient population and other related settings such as nonmetastatic RCC.
Subject(s)
Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/mortality , Kidney Neoplasms/genetics , Kidney Neoplasms/mortality , Models, Molecular , Aged , Area Under Curve , Biomarkers, Tumor , Canada , Carcinoma, Renal Cell/pathology , Female , Gene Expression Profiling , Humans , Kaplan-Meier Estimate , Kidney Neoplasms/pathology , Male , Middle Aged , Models, Statistical , Neoplasm Metastasis , Prognosis , Risk Factors , United StatesABSTRACT
BACKGROUND: Prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and interchange of hospital-associated strains carrying the staphylococcal chromosomal cassette mec-II (SCCmec-II) with those in the community (SCCmec-IV) has increased. This study assesses the impact of MRSA and different MRSA types on clinical outcomes, medication use, and antibiotic sensitivities. METHODS: MRSA isolates from CF patients at our center were typed by SCCmec- and pv(l) status. Patient characteristics, lung function and nutrition are compared between MRSA types and to age, gender and Pseudomonas aeruginosa matched patients with chronic methicillin sensitive S. aureus (MSSA) infection. RESULTS: Seventy-two percent of patients carry pv(l) negative SCCmec-II isolates. Seventeen percent of all MRSA were SCCmec-IV pv(l) positive (USA300). These patients were younger and fewer had chronic P. aeruginosa infection, whereas pv(l)-negative SCCmec-IV isolates show highest antibiotic resistance. Nutritional outcomes and FEV1 percent predicted (75.1 ± 2.7 versus 77.9 ± 2.7) did not differ in patients with MRSA compared to those with MSSA but MRSA patients received more pulmonary maintenance but not oral antibiotic medications. CONCLUSION: Patients with chronic MRSA are treated more intensely than age, gender and Pseudomonas aeruginosa matched MSSA-positive patients but clinical characteristics within MRSA patients vary depending on MRSA types.
