Survival In Caucasian Patients Research Articles

The Prognostic Value of Pretreatment Plasma Fibrinogen in Urological Cancers: A Systematic Review and Meta-analysis.

Objective:Growing evidence suggests pretreatment fibrinogen can serve as a prognostic marker in various malignancies. However, there are contradictory results about the prognostic role of fibrinogen in urological cancers. We conducted a meta-analysis to evaluate the association between pretreatment plasma fibrinogen and survival outcomes in urological cancers.Methods: After a systematic search of PubMed and Embase, we included 14 studies in our meta-analysis, and estimated hazard ratios (HRs) for overall survival (OS) and cancer-specific survival (CSS) using a fixed-effect model.Results: Our results indicate that pretreatment plasma fibrinogen is a prognostic factor in urological cancers (OS: HR=2.21, 95% CI=1.91-2.57, P<0.001, CSS: HR=2.67, 95% CI=2.23-3.19, P<0.001). Elevated pretreatment plasma fibrinogen is associated with poorer survival in prostate cancer (OS: HR=2.26, 95% CI=1.47-3.48, P<0.001; CSS: HR=2.42, 95% CI=1.44-4.07, P=0.001), renal cell carcinoma (OS: HR=2.13, 95% CI=1.75-2.61, P<0.001; CSS: HR=2.99, 95% CI=2.29-3.89, P<0.001) and upper tract urothelial carcinoma (OS: HR=2.34, 95% CI=1.81-3.02, P<0.001; CSS: HR=2.43, 95% CI=1.84-3.20, P<0.001). Subgroup analyses showed that plasma fibrinogen has a more negative impact on survival in Caucasian patients (OS: HR=2.52, 95% CI=1.95-3.25, P<0.001; CSS: HR=2.83, 95% CI=1.92-4.17, P<0.001) than Asian patients (OS: HR=2.07, 95% CI=1.73-2.49, P<0.001; CSS: HR=2.63, 95% CI=2.14-3.22, P<0.001). The prognostic value of fibrinogen is also consistent when stratified by different cut-off values.Conclusions: These results show that high pretreatment plasma fibrinogen levels can predict poorer OS and CSS in patients with urological cancers.

The CTLA-4 rs231775 GG genotype is associated with favorable 90-day survival in Caucasian patients with sepsis

Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a surface protein on T cells, that has an inhibitory effect on the host immune reaction and prevents overreaction of the immune system. Because the functional single-nucleotide polymorphism (SNP) rs231775 of the CTLA-4 gene is associated with autoimmune diseases and because of the critical role of the immune reaction in sepsis, we intended to examine the effect of this polymorphism on survival in patients with sepsis. 644 septic adult Caucasian patients were prospectively enrolled in this study. Patients were followed up for 90 days. Mortality risk within this period was defined as primary outcome parameter. Kaplan-Meier survival analysis revealed a significantly lower 90-day mortality risk among GG homozygous patients (n = 101) than among A allele carriers (n = 543; 22% and 32%, respectively; p = 0.03565). Furthermore, the CTLA-4 rs231775 GG genotype remained a significant covariate for 90-day mortality risk after controlling for confounders in the multivariate Cox regression analysis (hazard ratio: 0.624; 95% CI: 0.399–0.975; p = 0.03858). In conclusion, our study provides the first evidence for CTLA-4 rs231775 as a prognostic variable for the survival of patients with sepsis and emphasizes the need for further research to reveal potential functional associations between CTLA-4 and the immune pathophysiology of sepsis.

Lower frequency of TLR9 variant associated with protection from breast cancer among African Americans.

IntroductionToll-like receptor 9 (TLR9) is an innate immune system DNA-receptor that regulates tumor invasion and immunity in vitro. Low tumor TLR9 expression has been associated with poor survival in Caucasian patients with triple negative breast cancer (TNBC). African American (AA) patients with TNBC have worse prognosis than Caucasians but whether this is due to differences in tumor biology remains controversial. We studied the prognostic significance of tumor Toll like receptor-9 (TLR9) protein expression among African American (AA) triple negative breast cancer (TNBC) patients. Germline TLR9 variants in European Americans (EAs) and AAs were investigated, to determine their contribution to AA breast cancer risk.MethodsTLR9 expression was studied with immunohistochemistry in archival tumors. Exome Variant Server and The Cancer Genome Atlas were used to determine the genetic variation in the general EA and AA populations, and AA breast cancer cases. Minor allele frequencies (MAFs) were compared between EAs (n = 4300), AAs (n = 2203), and/or AA breast cancer cases (n = 131).ResultsThirty-two TLR9 variants had a statistically significant MAF difference between general EAs and AAs. Twenty-one of them affect a CpG site. Rs352140, a variant previously associated with protection from breast cancer, is more common in EAs than AAs (p = 2.20E-16). EAs had more synonymous alleles, while AAs had more rare coding alleles. Similar analyses comparing AA breast cancer cases with AA controls did not reveal any variant class differences; however, three previously unreported TLR9 variants were associated with late onset breast cancer. Although not statistically significant, rs352140 was observed less frequently in AA cases compared to controls. Tumor TLR9 protein expression was not associated with prognosis.ConclusionsTumor TLR9 expression is not associated with prognosis in AA TNBC. Significant differences were detected in TLR9 variant MAFs between EAs and AAs. They may affect TLR9 expression and function. Rs352140, which may protect from breast cancer, is 1.6 X more common among EAs. These findings call for a detailed analysis of the contribution of TLR9 to breast cancer pathophysiology and health disparities.

The FER rs4957796 TT genotype is associated with unfavorable 90-day survival in Caucasian patients with severe ARDS due to pneumonia

A recent genome-wide association study showed that a genetic variant within the FER gene is associated with survival in patients with sepsis due to pneumonia. Because severe pneumonia is the main cause of acute respiratory distress syndrome (ARDS), we aimed to investigate the effect of the FER polymorphism rs4957796 on the 90-day survival in patients with ARDS due to pneumonia. An assessment of a prospectively collected cohort of 441 patients with ARDS admitted to three intensive care units at the University Medical Centre identified 274 patients with ARDS due to pneumonia. The 90-day mortality risk was recorded as the primary outcome parameter. Sepsis-related organ failure assessment (SOFA) scores and organ support-free days were used as the secondary variables. FER rs4957796 TT-homozygous patients were compared with C-allele carriers. The survival analysis revealed a higher 90-day mortality risk among T homozygotes than among C-allele carriers (p = 0.0144) exclusively in patients with severe ARDS due to pneumonia. The FER rs4957796 TT genotype remained a significant covariate for the 90-day mortality risk in the multivariate analysis (hazard ratio, 4.62; 95% CI, 1.58–13.50; p = 0.0050). In conclusion, FER rs4957796 might act as a prognostic variable for survival in patients with severe ARDS due to pneumonia.

Association between the XRCC1 polymorphisms and clinical outcomes of advanced NSCLC treated with platinum-based chemotherapy: a meta-analysis based on the PRISMA statement

BackgroundBase excision repair (BER) pathway is a DNA repair pathway that is important in carcinogenesis and in response to DNA-damaging chemotherapy. XRCC1 is one of important molecular markers for BER. So far, the role of XRCC1 polymorphisms with clinical outcomes of advanced NSCLC treated with platinum-based chemotherapy is inconclusive. To explore the relationship between XRCC1 polymorphisms and platinum-based chemotherapy in advanced NSCLC patients, we performed this meta-analysis.MethodsCrude odds ratios (ORs), Cox proportional hazard ratios (HRs) with the corresponding 95% confidence intervals (CIs) were adopted to assess the strength of association between XRCC1 polymorphisms and response rate, Overall survival (OS) and progression free survival (PFS) of advanced NSCLC treated with platinum-based chemotherapy. Q test and I2 test were used for the assessment of heterogeneity. Subgroup analyses were conducted when heterogeneity exists. Begg’s funnel plots and Egger’s linear regression test were used to estimate publication bias. Sensitivity analysis was performed to evaluate the stability of the result.ResultsA total of 19 studies including 2815 individuals were eligible for the analysis, results showed XRCC1 194Arg allele was negatively associated with the objective response rate relative to 194Trp, and results of homozygous model, dominant model and heterozygous model suggested a gene dosage effect negative correlation between 194Arg allele and objective response rate(ArgArg vs TrpTrp: OR = 0.64(95%CI: 0.44-0.91); ArgArg + TrpArg vs TrpTrp: OR = 0.79(95%CI: 0.57-1.11); TrpArg vs TrpTrp: OR = 1.05(95%CI: 0.73-1.51)). XRCC1 399Gln may indicate favorable overall survival (GlnGln + GlnArg vs ArgArg: HR = 0.65(95%CI: 0.43–0.98)) and favorable PFS (GlnGln vs ArgArg: HR = 0.72(95%CI: 0.48–0.97)) in Asian patients; while in Caucasian patients, XRCC1 399Gln indicated poorer overall survival (GlnGln vs ArgArg: HR = 2.29(95%CI: 1.25–3.33)).ConclusionsOur results indicated that in NSCLC patients treated with platinum-based regimen, XRCC1 194Arg allele suggest poor objective response rate, the GlnGln genotype of XRCC1 399 suggest poorer overall survival in Caucasian patients, and longer PFS in Asian patients.

Abstract 2249: Integrated multi-level omics-based biomarker models for ovarian cancer survival

Abstract Background: Although a number of prognostic biomarkers for ovarian cancer have been proposed, the pool of clinically useful biomarkers remains small. While the predictive power of individual biomarkers may be weak, the advent of more affordable high-throughput technologies and readily available “omics” level data point toward the possibility of high performance biomarker panels. In this study, we used tumor-based somatic mutation, mRNA and miRNA expression, and DNA methylation data from The Cancer Genome Atlas (TCGA) to construct integrated biomarker models for overall and progression-free survival. Methods: The somatic mutations, mRNA expression, and DNA methylation of 451 candidate genes, as well as the expression of the miRNAs targeting them, were individually analyzed for association with overall and progression-free survival in 488 TCGA serous cystadenocarcinoma patients of predominantly Caucasian descent. Following correction for multiple comparisons, molecular variations associated with survival were combined to construct integrated cross-validated prediction models for overall and progression-free survival. The discriminative power of these models was then evaluated for 1-, 3-, and 5-year overall and progression-free survival using ROC analysis. Results: Our cross-validated integrated molecular models were demonstrated to predict 5-year overall survival in the total patient pool with a ROC AUC of 0.801 and 5-year overall and progression-free survival in Caucasian patients with ROC AUCs of 0.866 and 0.809, respectively. Conclusions: Our findings suggest the potential utility of our multi-omics-based biomarker models in helping to inform clinical decisions following ovarian cancer diagnosis. Although extensive efforts were made to maximize the predictive potential of our models, further retrospective and prospective validation efforts are necessary before their clinical utility can be accurately assessed. Citation Format: Alan Fu, Shen-Chih Chang, Aileen Baecker, Helena R. Chang, Zuo-Feng Zhang. Integrated multi-level omics-based biomarker models for ovarian cancer survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2249. doi:10.1158/1538-7445.AM2017-2249

Systemic immune-inflammation index to predict survival in Caucasian patients with metastatic urothelial carcinoma.

e16015 Background: The systemic immune-inflammation index (SII) is a prognostic factor in various malignancies that probably reflects a state of immunity. The objective of this retrospective analysis was to explore prognostic value of the SII at baseline and at week 6 during first-line platinum-based chemotherapy in Caucasian population with metastatic urothelial cancer (MUC). Methods: We evaluated 185 consecutive MUC (152 bladder, 72 upper tract) patients (139 men) treated with first-line platinum-based chemotherapy at National Cancer Institute between 2000-2015. Median Karnofsky index was 90% (30–100%), visceral metastases were present in 86 patients. SII was based on platelets (P), neutrophils (N) and lymphocytes (L) counts defined as PxN/L. Progression-free survival (PFS), overall survival (OS) and their 95% CI were estimated by Kaplan-Meier method and compared with logrank test. The study population was dichotomized by median into high SII and low SII groups. Multivariate Cox regression analysis included Karnofski index, status of visceral metastases together with baseline SII and SII at week 6, respectively. Results: At median follow-up 10 months (1-139 months), 170 patients experienced disease progression and 168 of them died.Patients with low SII at baseline had significantly better PFS and OS opposite to those with high SII (HR = 0.62, 95% CI 0.45-0.84 for PFS and HR = 0.52, 95% CI 0.38-0.71 for OS, respectively). Similarly, patients with low SII at 6 weeks had significantly better PFS and OS compared to those with high SII (HR = 0.61, 95% CI 0.45-0.83 for PFS and HR = 0.54, 95% CI 0.40–0.74 for OS, respectively). Multivariate analysis confirmed independent prognostic value of baseline SII and SII at week 6 for PFS and OS. Conclusions: Both, the SII at baseline and at week 6 during treatment with first-line chemotherapy represent independent prognostic factors for Caucasian population with MUC. Based on SII, patients could be stratified into future clinical trials. MUC patients with high SII might be candidates for an experimental first-line treatment.

Abstract 4594: Serum microRNA signatures predict recurrence and survival in Caucasian patients with early stage non-small cell lung cancer

Abstract Early stage non-small cell lung cancer (NSCLC) patients can be curatively treated by surgery alone or with adjuvant chemotherapy. However, about half of patients develop recurrence and eventually die of this disease. The purpose of this study is to identify circulating microRNAs (miRNA) as minimally invasive biomarkers for the prognosis of early stage NSCLC that may allow personalized clinical management of early stage NSCLC patients. Using a large series of 171 stage I and II NSCLC Caucasian patients, we screened and validated serum miRNA signatures predictive of recurrence and survival in these patients. We identified six miRNA expression ratios that were associated with recurrence and three miRNA expression ratios that were associated with overall survival. In Receiver Operating Characteristic (ROC) curve analysis, the area under the curve (AUC) for clinical variable-only model was 0.714 for recurrence and 0.678 for survival; however, the AUC increased to 0.878 for recurrence and 0.796 for survival when the miRNA ratio signatures were added to the recurrence and survival models respectively. The patients in the high risk group as defined by the 6 miRNA ratio signature exhibited an approximately 5-fold increased risk of develop recurrence compared with low risk patients. In survival analysis, the death rate increased over 4-fold in the high risk group compared with the low risk group. Our results suggest that the miRNA ratio signatures could serve as prognostic biomarkers for early stage NSCLC. Citation Format: Liren Zhang, Jack A. Roth, Jie Lian, Yuanqing Ye, Jian Gu, Xifeng Wu. Serum microRNA signatures predict recurrence and survival in Caucasian patients with early stage non-small cell lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4594. doi:10.1158/1538-7445.AM2015-4594

Racial Disparities in Survival and Age-Related Outcome in Postsurgery Breast Cancer Patients in a New York City Community Hospital

Breast cancer survival has significantly improved over the past two decades. However, the diagnosis of breast cancer is lower and the mortality rate remains higher, in African American women (AA) compared to Caucasian-American women. The purpose of this investigation is to analyze postoperative events that may affect breast cancer survival. This is a retrospective analysis of prospectively collected data from The Brooklyn Hospital Center cancer registry from 1997 to 2010. Of the 1538 patients in the registry, 1226 are AA and 269 are Caucasian. The study was divided into two time periods, 1997–2004 (period A) and 2005–2010 (period B), in order to assess the effect of treatment outcomes on survival. During period A, 5-year survival probabilities of 75.37%, 74.53%, and 78.70% were seen among all patients, AA women and Caucasian women, respectively. These probabilities increased to 87.62%, 87.15% and 89.99% in period B. Improved survival in AA women may be attributed to the use of adjuvant chemotherapy, radiation, and hormonal therapy. Improved survival in Caucasian patients was attributed to the use of radiation therapy, as well as earlier detection resulting in more favorable tumor grades and pathological stages.

History of tuberculosis as an independent prognostic factor for lung cancer survival

IntroductionIt is well known that pulmonary tuberculosis is associated with an increased risk of lung cancer. We investigated whether a history of pulmonary tuberculosis is an independent risk factor for lung cancer survival in Caucasian patients. MethodsThe data of the prospective population-based cohort of The Rotterdam Study were used. During a mean follow-up time of 18 years, there were 214 incident cases of pathology-proven lung cancer in a source population of 7983 study participants. History of tuberculosis was assessed at baseline by interviewers using standardized questionnaires. Associations of lung cancer survival with the occurrence of pulmonary tuberculosis were assessed using Cox's proportional hazard regression analysis adjusted for age, gender, pack-years, educational level and tumor stage. ResultsA history of tuberculosis was reported in 13 of the 214 subjects with lung cancer. The survival of patients with lung cancer was significantly shorter in subjects with a history of pulmonary tuberculosis (HR=2.36, CI95%: 1.1–4.9), than in subjects without a history of pulmonary tuberculosis with a mean difference of 311 days. ConclusionThe presence of a history of pulmonary tuberculosis may be an important prognostic factor in the survival of lung cancer.

Association of a CYP17 Polymorphism with Overall Survival in Caucasian Patients with Androgen-Independent Prostate Cancer

To investigate the association between a cytochrome P450 17alpha-hydroxylase gene (CYP17) polymorphism and survival in Caucasian patients with androgen-independent prostate cancer (AIPC). The study used 222 samples acquired from Caucasian patients with AIPC. The CYP17 polymorphism (-34T>C) was analyzed using polymerase chain reaction amplification followed by restriction fragment length polymorphism detection. No significant differences were observed in the frequencies of the CYP17 genotype in relation to categorized Gleason scores, age at diagnosis, or hormone therapy. The median survival was significantly longer in 126 patients with the CYP17 A2 allele (8.9 years) genotype than in 96 patients with the A1 allele (6.7 years) genotype (P = 0.040 by log-rank test). Similarly, the estimated survival probability at 10 years (24% in A1 allele versus 43% in A2 allele) showed a statistically significant difference between the two groups (P = 0.002 by the permutation test). These results suggest that the CYP17 polymorphism is associated with overall survival in patients with AIPC.

Angiotensin-converting-enzyme insertion/deletion genotype and long-term renal allograft survival.

Increased activity of the renin-angiotensin system has been implicated in decreased long-term survival of renal allografts. Recent studies suggest that a deletion variant of the angiotensin-converting enzyme, associated with increased humoral and tissue activity of this enzyme, may be a risk factor for the development of diabetic nephropathy and the progression of IgA nephropathy. The present study was conducted to determine whether the deletion variant of the angiotensin-converting-enzyme gene influences the long-term outcome in renal-transplant recipients. We examined the relationship between recipient angiotensin-converting-enzyme genotype and clinical outcome in patients with a surviving allograft of at least 10 years (median survival 156 months, n= 86). Patients with an allograft survival of less than 3 years served as controls (median survival 10.4 months, n=87). Genotype distribution in long-term renal allograft survivors (II, 18; ID, 41; DD, 27; qD, 0.55) was similar to that in the control group (II, 12; ID, 53; DD, 22; qD, 0.56), and there were no significant differences between the genotypic groups in either cases or controls. Long-term survivors were more often female (58 vs 38%) and less often hypertensive (67 vs 77%). Both recipient and donor age were markedly lower in the long-term survivor group, whereas number of HLA mismatches and cold ischaemia time were comparable between cases and controls. This study does not support the hypothesis that the angiotensin-converting-enzyme insertion/deletion polymorphism is an important determinant of long-term transplant survival in Caucasian patients undergoing renal transplantation.

Angiotensin-converting enzyme genotype and renal allograft survival.

Increased activity of the renin-angiotensin system has been implicated in decreased, long-term survival of renal allografts. Recent studies suggest that a deletion variant of the angiotensin-converting enzyme, associated with increased humoral and tissue activity of this enzyme, is a risk factor for the development of diabetic nephropathy and the progression of IgA nephropathy. To determine whether the deletion variant of the angiotensin-converting enzyme gene influences the long-term outcome in renal transplant recipients, the relationship between donor and recipient angiotensin-converting enzyme genotype and clinical outcome were examined over a follow-up period up to 30 mo in a cohort of 269 Caucasian patients undergoing kidney transplantation between 1988 and 1993. In a subsequent case control study, the frequencies of the angiotensin-converting enzyme genotype were compared in a group of Caucasian patients with a graft survival of less than 3 yr (mean survival, 11 mo; n = 328) with the frequencies in patients with a graft survival of at least 3 yr (mean survival, 65 mo, n = 461). Neither in the cohort nor in the case control study was there a significant effect of recipient or donor angiotensin-converting enzyme genotype on transplant survival. Furthermore, the frequency of the angiotensin-converting enzyme deletion allele both in recipients and donors was similar to that reported in Caucasian controls. This study, therefore, does not support the hypothesis that the recipient or donor angiotensin-converting enzyme insertion/deletion polymorphism is an important determinant of transplant survival in Caucasian patients undergoing renal transplantation.

Superior renal graft survival in caucasian patients with DR types associated with insulin dependent diabetes mellitus (IDDM), systemic lupus erythematosus (SLE), and goodpasture's syndrome (GP): [formula omitted] and PI Terasaki, UCLA Tissue Typing Laboratory, Los Angeles, CA

Superior renal graft survival in caucasian patients with DR types associated with insulin dependent diabetes mellitus (IDDM), systemic lupus erythematosus (SLE), and goodpasture's syndrome (GP): [formula omitted] and PI Terasaki, UCLA Tissue Typing Laboratory, Los Angeles, CA