scholarly journals Immunogenomic determinants of tumor microenvironment correlate with superior survival in high-risk neuroblastoma

2021 ◽  
Vol 9 (7) ◽  
pp. e002417
Author(s):  
Riyue Bao ◽  
Stefani Spranger ◽  
Kyle Hernandez ◽  
Yuanyuan Zha ◽  
Peter Pytel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Overall Survival ◽  
T Cell ◽  
High Risk ◽  
Proportional Hazards ◽  
Checkpoint Inhibitors ◽  
Gene Expression Signature ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Models ◽  
Immune Exclusion

BackgroundTumor-infiltrating CD8+ T cells and neoantigens are predictors of a favorable prognosis and response to immunotherapy with checkpoint inhibitors in many types of adult cancer, but little is known about their role in pediatric malignancies. Here, we analyzed the prognostic strength of T cell-inflamed gene expression and neoantigen load in high-risk neuroblastoma. We also compared transcriptional programs in T cell-inflamed and non-T cell-inflamed high-risk neuroblastomas to investigate possible mechanisms of immune exclusion.MethodsA defined T cell-inflamed gene expression signature was used to categorize high-risk neuroblastomas in the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) program (n=123), and the Gabriella Miller Kids First (GMKF) program (n=48) into T cell-inflamed, non-T cell-inflamed, and intermediate groups. Associations between the T cell-inflamed and non-T cell-inflamed group, MYCN amplification, and survival were analyzed by Cox proportional hazards models. Additional survival analysis was conducted after integrating neoantigen load predicted from somatic mutations. Pathways activated in non-T cell-inflamed relative to T cell-inflamed tumors were analyzed using causal network analysis.ResultsPatients with T cell-inflamed high-risk tumors showed improved overall survival compared with those with non-T cell-inflamed tumors (p<0.05), independent of MYCN amplification status, in both TARGET and GMKF cohorts. Higher neoantigen load was also associated with better event-free and overall survival (p<0.005) and was independent of the T cell-inflamed signature. Activation of MYCN, ASCL1, SOX11, and KMT2A transcriptional programs was inversely correlated with the T cell-inflamed signature in both cohorts.ConclusionsOur results indicate that tumors from children with high-risk neuroblastoma harboring a strong T cell-inflamed signature have a more favorable clinical outcome, and neoantigen load is a prognosis predictor, independent of T cell inflammation. Strategies to target SOX11 and other signaling pathways associated with non-T cell-inflamed tumors should be pursued as potential immune-potentiating interventions.

scholarly journals Integrative transcriptome analysis of malignant pleural mesothelioma reveals a clinically relevant immune-based classification

2021 ◽  
Vol 9 (2) ◽  
pp. e001601
Author(s):  
Ania Alay ◽  
David Cordero ◽  
Sara Hijazo-Pechero ◽  
Elisabet Aliagas ◽  
Adriana Lopez-Doriga ◽  
...  
Keyword(s):  
Gene Expression ◽  
Overall Survival ◽  
Malignant Pleural Mesothelioma ◽  
Drug Response ◽  
Proportional Hazards ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Cox Proportional Hazards ◽  
Transcriptional Level ◽  
Pleural Mesothelioma

BackgroundMalignant pleural mesothelioma (MPM) is a rare and aggressive neoplasia affecting the lung mesothelium. Immune checkpoint inhibitors (ICI) in MPM have not been extremely successful, likely due to poor identification of suitable candidate patients for the therapy. We aimed to identify cellular immune fractions associated with clinical outcome and classify patients with MPM based on their immune contexture. For each defined group, we sought for molecular specificities that could help further define our MPM classification at the genomic and transcriptomic level, as well as identify differential therapeutic strategies based on transcriptional signatures predictive of drug response.MethodsThe abundance of 20 immune cell fractions in 516 MPM samples from 7 gene expression datasets was inferred using gene set variation analysis. Identification of clinically relevant fractions was performed with Cox proportional-hazards models adjusted for age, stage, sex, and tumor histology. Immune-based groups were defined based on the identified fractions.ResultsT-helper 2 (TH2) and cytotoxic T (TC) cells were found to be consistently associated with overall survival. Three immune clusters (IG) were subsequently defined based on TH2 and TC immune infiltration levels: IG1 (54.5%) was characterized by high TH2 and low TC levels, IG2 (37%) had either low or high levels of both fractions, and IG3 (8.5%) was defined by low TH2 and high TC levels. IG1 and IG3 groups were associated with worse and better overall survival, respectively. While no differential genomic alterations were identified among immune groups, at the transcriptional level, IG1 samples showed upregulation of proliferation signatures, while IG3 samples presented upregulation of immune and inflammation-related pathways. Finally, the integration of gene expression with functional signatures of drug response showed that IG3 patients might be more likely to respond to ICI.ConclusionsThis study identifies a novel immune-based signature with potential clinical relevance based on TH2 and TC levels, unveiling a fraction of patients with MPM with better prognosis and who might benefit from immune-based therapies. Molecular specificities of the different groups might be used to tailor specific potential therapies in the future.

scholarly journals Integrative transcriptome analysis of malignant pleural mesothelioma reveals a clinically relevant immune-based classification

2020 ◽  
Author(s):  
Ania Alay ◽  
David Cordero ◽  
Sara Hijazo-Pechero ◽  
Elisabet Aliagas ◽  
Adriana Lopez-Doriga ◽  
...  
Keyword(s):  
Gene Expression ◽  
Overall Survival ◽  
Malignant Pleural Mesothelioma ◽  
Drug Response ◽  
Proportional Hazards ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Cox Proportional Hazards ◽  
Transcriptional Level ◽  
Pleural Mesothelioma

Background. Malignant pleural mesothelioma (MPM) is a rare and aggressive neoplasia affecting the lung mesothelium. Immune checkpoint inhibitors (ICI) in MPM have not been extremely successful, likely due to poor identification of suitable candidate patients for the therapy. We aimed to identify cellular immune fractions associated with clinical outcome and classify MPM patients based on their immune contexture. For each defined group, we sought for molecular specificities that could help further define our MPM classification at the genomic and transcriptomic level, as well as identify differential therapeutic strategies based on transcriptional signatures predictive of drug response. Methods. The abundance of 20 immune cell fractions in 516 MPM samples from 7 gene expression datasets was inferred using Gene Set Variation Analysis. Identification of clinically relevant fractions was performed with Cox Proportional-Hazards Models adjusted for age, stage, sex, and tumor histology. Immune-based groups were identified using unsupervised classification. Results. T-Helper 2 (TH2) and cytotoxic T (TC) cells were found to be consistently associated with overall survival. Three immune clusters (IG) were subsequently defined based on TH2 and TC immune infiltration levels: IG1 (54.5%) was characterized by high TH2 and low TC levels, IG2 (37%) had either low or high levels of both fractions, and IG3 (8.5%) was defined by low TH2and high TC levels. IG1 and IG3 groups were associated with worse and better overall survival, respectively. The three groups showed differential molecular profiles, with IG1 enriched for CDKN2A and IFN-related genes deletions. At the transcriptional level, IG1 samples showed upregulation of proliferation signatures, while IG3 samples presented upregulation of immune and inflammation-related pathways. Finally, the integration of gene expression with functional signatures of drug response showed that IG3 patients might be more likely to respond to ICI, while IG1 patients could be more sensitive to PARP inhibitors. Conclusions. This study identifies a novel immune-based signature with potential clinical relevance based on TH2 and TC levels, unveiling a fraction of MPM patients with better prognosis and who might benefit from immune-based therapies. Genomic and transcriptomic specificities of the different groups could be used to tailor potential therapies in the future.

scholarly journals A Five-Gene Expression Signature Predicts Clinical Outcome of Ovarian Serous Cystadenocarcinoma

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Li-Wei Liu ◽  
Qiuhao Zhang ◽  
Wenna Guo ◽  
Kun Qian ◽  
Qiang Wang
Keyword(s):  
Gene Expression ◽  
Survival Time ◽  
Proportional Hazards ◽  
Gene Expression Signature ◽  
High Specificity ◽  
Cox Proportional Hazards ◽  
Assessment Model ◽  
Serous Cystadenocarcinoma ◽  
Specificity And Sensitivity ◽  
Risk Patients

Ovarian serous cystadenocarcinoma is a common malignant tumor of female genital organs. Treatment is generally less effective as patients are usually diagnosed in the late stage. Therefore, a well-designed prognostic marker provides valuable data for optimizing therapy. In this study, we analyzed 303 samples of ovarian serous cystadenocarcinoma and the corresponding RNA-seq data. We observed the correlation between gene expression and patients’ survival and eventually established a risk assessment model of five factors using Cox proportional hazards regression analysis. We found that the survival time in high-risk patients was significantly shorter than in low-risk patients in both training and testing sets after Kaplan-Meier analysis. The AUROC value was 0.67 when predicting the survival time in testing set, which indicates a relatively high specificity and sensitivity. The results suggest diagnostic and therapeutic applications of our five-gene model for ovarian serous cystadenocarcinoma.

Quantitative Gene Expression Analysis of Surrogate Markers for Genetic Risk Groups and Survival in CLL

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4170-4170
Author(s):  
Dirk Kienle ◽  
Axel Benner ◽  
Dirk Winkler ◽  
Manfred Hensel ◽  
Riccardo Dalla-Favera ◽  
...  
Keyword(s):  
Gene Expression ◽  
Overall Survival ◽  
Survival Analysis ◽  
Genetic Risk ◽  
Proportional Hazards ◽  
Risk Groups ◽  
Cox Proportional Hazards ◽  
Surrogate Markers ◽  
Mutation Status ◽  
Binet Stage

Abstract In CLL, a variety of surrogate markers for individual genetic features, mostly the VH mutation status, were proposed from gene expression analyses. However, their detailed relation to specific genetic subsets such as V3-21 usage, del11q22-q23 (11q−), and del17p13 (17p−), and their prognostic value in relation to established factors is not elucidated yet. Gene expression markers (ADAM29, ATM, CLLU1, DMD, GLO1, HS1, KIAA0977, LPL, MGC9913, PCDH9, PEG10, SEPT10, TCF7, TP53, Vimentin, ZAP-70, ZNF2) were evaluated using real-time quantitative RT-PCR (RQ-PCR) in purified samples of 151 patients. VH sequencing and FISH screening for genomic aberrations were carried out for all cases, survival information was available for 133 cases. Logistic regression was performed to test the predictive value of gene expression for genetic risk groups, Cox proportional hazards statistics for survival analysis. VH mutation status was best assigned by LPL and ZAP70, followed by TCF7, a marker with a characteristic overexpression in VH mutated CLL patients (correct VH prediction in 83%, 83%, and 75% of the patients, respectively). A similar rate of correct VH assignments was achieved in the subgroup of patients with 11q− or 17p− when using these markers (88%, 86%, and 79%, respectively). In contrast to LPL and TCF7, most of the patients with V3-21 usage were recognized as risk patients by ZAP70 independently of the VH status. Therefore, ZAP70 yielded the best results for the overall recognition of patients with a genetic risk constellation (VH unmutated or V3-21 usage or 11q− or 17p−). Comparison of ZAP-70 determination by RQPCR and flow cytometry was performed for 72 patients and revealed 30% of discordant cases. Thereof, the majority was VH unmutated (including several cases with 11q− or 17p−) showing ZAP-70 negativity by FACS and positivity by RQ-PCR. In multivariate analysis of time to first treatment (TFT), ADAM29 was an independent prognostic factor besides the VH status and Binet stage. In overall survival analysis including the gene expression variables only, LPL was the strongest predictor for overall survival. When genetic and clinical factors were added to this analysis, V3-21 usage, 17p−, age, binet stage, and expression of ATM, ADAM29, SEPT10, and TCL1 were identified as significant prognostic factors. In conclusion, novel gene expression markers allow screening for patients at risk but can not fully substitute for the genetic factors, which should therefore at present remain the basis for risk stratification approaches. Some of the novel markers appear to have a prognostic relevance independently of the established factors, which points to relevant biologic and clinical implications demanding further investigation.

The Majority of Myeloma Patients Are Vitamin D Deficient, Unrelated to Survival or Cytogenetics

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5336-5336 ◽  
Author(s):  
Samantha Hudzik ◽  
Beau Snoad ◽  
Luay Mousa ◽  
Douglas W Sborov ◽  
Nita Williams ◽  
...  
Keyword(s):  
Vitamin D ◽  
Overall Survival ◽  
High Risk ◽  
Bone Disease ◽  
Proportional Hazards ◽  
Conflicts Of Interest ◽  
Cox Proportional Hazards ◽  
Plasma Cell Dyscrasia ◽  
Markers Of Inflammation ◽  
Vitamin D Levels

Abstract Introduction: Since a link between solar radiation, vitamin D production, and decreased colon cancer mortality was established in 1980, there has been increasing interest in vitamin D and cancer, suggesting that higher vitamin D levels improve overall survival, specifically in breast and colorectal cancer (Maalmi H et al, Eur J Canc, May-2014, PMID 24582912), but also in follicular lymphoma (Kelly JL, J Clin Onc, 1-May-2015, PMID 25823738). In myeloma, largest published series is from the Mayo Clinic reporting on 148 newly diagnosed MM patients for which no survival association was found, but there were associations between low 25-OH-Vit D (<20 ng/mL) and higher serum CRP, serum creatinine, and ISS stage (Ng AC, Am J. Heme, Jul-2009, PMID 19415724); we wanted to expand on their trailblazing analysis. Cytogenetically high risk myeloma characterized by the amplification of 1q21 is associated with increased serum levels of soluble IL-6 receptor (sIL-6r) (Stephens OW, Blood, 2012, PMID 22072558) which may be associated with other markers of inflammation, e.g. CRP, creatinine, and b2microglobulin. Methods: The Buckeye Myeloma Registry (OSU 10115) opened in 2011 to enroll any patient with a plasma cell dyscrasia. Serum total 25-OH-Vitamin D was measured at the time of the initial clinic visit to the myeloma group at Ohio State. Results: Of a total of 843 patients, 115 (13.6%), 53 (6.3%) with SMM, and 675 (80.1%) with MM. In the 675 MM patients, the median age was 64 y.o. (range 28-95), 14.5% African-American and the remainder Caucasian, with 28.6% ISS stage 1, 48.7% ISS stage 2, 21.9% ISS stage 3, and 24.5% unknown. At diagnosis for the MM patients, 67% presented with lytic bone disease. Out of 675 MM patients, there were 52 (7.7%) patients with < 10 ng/mL 25-OH-Vit D, 394 (51%) with low vit D (10-30 ng/mL), and 229 (39%) for 25-OH-Vit D 30-100 ng/mL. There was no correlation between 25-OH-Vit D and BMI or creatinine, but there was a strong correlation with race (r=0.18, p<0.000026). Among the MM patients, log-rank [Mantel-Cox] analysis of overall survival with serum 25-OH-Vit D including all groups demonstrated no significant differences (p=0.9725) with only 101 events. There was no correlation between 25-OH-Vit D and the presence on CD138-selected FISH of 1q21 amplification (p=0.196), 17p (p53) deletion (p=0.68), or 13q deletion (p=0.812). Conclusion: The majority of myeloma patients are vitamin D deficient, but this was not associated with worsened overall survival or with high risk cytogenetics. Cox proportional hazards analyses of survival adjusted for significant univariate covariates will be presented at the meeting. Correlations with presence or absence of diffuse lytic bone disease, severity of renal insufficiency, and race will also be presented at the meeting. Disclosures No relevant conflicts of interest to declare.

Evidence for a field effect in early prostate cancer (PCa): Gene expression profiles in normal-appearing prostate tissue (NT) adjacent to tumor (T) as predictors of clinical outcome.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5029-5029 ◽  
Author(s):  
Eric A. Klein ◽  
Sara Moscovita Falzarano ◽  
Nan Zhang ◽  
Dejan Knezevic ◽  
Tara Maddala ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Field Effect ◽  
Proportional Hazards ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cox Proportional Hazards ◽  
Clinical Recurrence ◽  
Molecular Alterations ◽  
Cox Proportional Hazards Models

5029 Background: We previously identified genes whose expression predicts aggressive PCa (clinical recurrence (cR), prostate cancer death (PCD), adverse pathology) when assessed in histologically heterogeneous tumor foci and in biopsies (Klein ASCO 2012). These results enabled the definition of a multi-gene Genomic Prostate Score (GPS), which has been clinically validated (Cooperberg AUA 2013). There is interest regarding a possible field effect in PCa, i.e. molecular alterations throughout the gland that may influence PCa development. We conducted exploratory analyses to evaluate gene expression, including GPS, in adjacent normal-appearing tissue (NT) for prediction of cR and PCD. Methods: Cohort sampling was used to select 127 patients with and 374 without cR from 2,641 patients treated with RP for T1/T2 PCa. Expression of 732 genes was measured by qRT-PCR separately in T and NT (defined as > 3 mm from T) specimens. GPS (0-100 units) was determined using the genes and algorithm from the validation study. Analysis used Cox proportional hazards models and Storey’s false discovery rate (FDR) control. Results: 410 evaluable patients had paired T and NT. Of the 405 genes which were predictive of outcome in T (FDR < 20%), 289 (71%) showed similar but weaker effects in NT. 47 genes were associated with cR in NT (FDR < 20%), of which 34 also concordantly predicted cR in T (FDR < 20%). GPS assessed in NT significantly predicted time to cR (HR/20 units = 1.8; 95% CI: 1.3-2.4; p< 0.001) and PCD (HR/20 units = 1.9; 95% CI: 1.2-3.0; p = 0.005) but was less predictive than GPS in T (HR/20 units = 4.8 for cR; 95% CI: 3.7-6.2; p < 0.001 and HR/20 units = 6.9 for PCD; 95% CI: 4.4-10.7; p < 0.001). The strongest components of GPS in predicting cR and PCD in NT were stromal response and androgen signaling genes (p < 0.05); proliferation and cellular organization genes did not consistently provide a significant contribution in NT. Conclusions: These data indicate that gene expression profiles, including GPS, can predict outcome in NT, albeit more weakly than in tumor. These findings suggest that there is an underlying field effect associated with the development of aggressive PCa.

Antiandrogen withdrawal (AAWD) in patients (pts) with prostate cancer (PCa): Retrospective analysis of data from the South Australian Prostate Cancer Clinical Outcome Collaborative (SA-PCCOC).

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 240-240
Author(s):  
Sina Vatandoust ◽  
Ganessan Kichenadasse ◽  
Michael E O'Callaghan ◽  
Tina Kopsaftis ◽  
Scott Walsh ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Proportional Hazards ◽  
South Australia ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Risk Of Death ◽  
Cox Proportional Hazards Models ◽  
Australian State ◽  
Chi Squared

240 Background: In 15-30% of pts with metastatic PCa who progress on Maximal Androgen Blockade (MAB), withdrawal of the antiandrogen agent (AAWD) and continuing the LHRH agonist alone, leads to PSA decreases of ≥50% and prolonged progression free survival. Here we describe patient and disease characteristics, treatment history and outcomes of pts who have been managed with AAWD. Methods: Data were obtained from SA-PCCOC (a longitudinal, observational registry of biopsy-proven PCa cases, throughout the Australian state of South Australia since 1998). Proportions were compared using a Chi squared test. A multivariable model used competing risks (Fine and Gray) and Cox proportional Hazards models to assess overall survival and Prostate cancer specific mortality (PCSM). Survival was calculated from the date of rising PSA for patients on LHRH and AA. Results: 140 pts were found to have MAB. Of these, 31(22.1%) had AAWD. In the AAWD group, median age was 81y (51-95). Age at diagnosis, Gleason score at biopsy and diagnostic PSA were not significantly different amongst the two groups. Treatment PSA was significantly lower in the AAWD group (20.55 (range 0.6-9,995) vs 50.50 (range 0.95-4378) p= 0.02). There was a significant association of AAWD with PCSM (sHR 0.35, 95% CI 0.16-0.76; p = 0.008). Also significant in the model was prior time on hormones (sHR [per month increase] 0.96 95% CI 0.95-0.98, p<0.001). There was also a significant association of AAWD with overall survival (HR 0.22, 95% CI 0.10-0.46; p <0.001). Again, prior time on hormones was also significant (HR [per month increase] 0.96 95% CI 0.95-0.98, p<0.001). Multivariate analysis was performed on data from 80 pts (60 pts omitted due to missing data). Conclusions: Pts in whom AAWD was used were older and had lower treatment PSA. In this small cohort, AAWD was associated with both reduced PCSM and overall risk of death. The time spent on MAB also appeared to be significant. This retrospective observational study may be subject to confounding, however the observation warrants further investigation in larger cohorts and in a prospective setting.

Neutrophils lymphocyte ratio role in predicting response to checkpoint inhibitors in metastatic non-small lung cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20646-e20646
Author(s):  
Hosam Hakim ◽  
Ahmed Abdalla ◽  
Tarik H. Hadid
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Proportional Hazards ◽  
Checkpoint Inhibitors ◽  
Statistical Significance ◽  
Immune Therapy ◽  
Cox Proportional Hazards ◽  
P Value ◽  
Lymphocyte Ratio ◽  
Metastatic Nsclc

e20646 Background: There have been numerous advances in the management of metastatic lung cancer, including targeted therapy against certain mutations in cancer cells and later developing immune therapy with check point inhibitors.From the pre-immune therapy era, a simple blood test allowing the calculation of the neutrophil-to-lymphocyte ratio (NLR) was established as a strong prognostic marker associated with worse overall survival (OS) in several tumor types including non-small cell lung cancer (NSCLC). Methods: We have retrospectively reviewed electronic medical records for patients with Metastatic NSCLC whom received at least one dose of Checkpoint Inhibitors from January 2014 till January 2019 in Van Eslander Cancer Center.The analysis was done using SPSS v. 25.0 and a p-value of 0.05 or less was considered to indicate statistical significance. A univariant analysis was done using Student’s t-test, the Mann-Whitney U test and the chi-squared test. Survival analysis was conducted using Kaplan Meier methodology as well as Cox proportional hazards models. Results: There were 80 patients with metastatic NSCLC received at least one dose of a checkpoint inhibitor. Median age was 63.9 ± 9.3; Males were 45%; Whites were 62.5%. 67.5% of patient had adenocarcinoma and 24% had squamous cell carcinoma. Twenty patients had brain metastasis (25%) and nineteen patients had liver metastasis (24.6%). Eleven patients (13.8%) had PDL-1 greater than 50% and 11 patients (13.8%) had PDL-1 between 1%-50% and 22 patients (27.5%) had negative PD-L1 status. 18.8% received immunotherapy as a first-line treatment and 65% got immunotherapy on their second line and 16.3% had immunotherapy as the third line of treatment or more. Sixty-one patients (76.2%) received Nivolumab and nineteen patients (23.8%) received pembrolizumab. Mean duration of immunotherapy was 13.7 months ± 20.7. Mean NLR was 6.1 ± 5. Patient with NLR > 5:1 had statistically significant higher progression-free survival (PFS) 27.5 months compared to 12 months P = 0.02. Also, Patients with baseline NLR > 5:1 had a trend toward higher median overall survival (OS) but was not statistically significant 41 months compared to 12 months P = 0.08. Conclusions: Our data showed similar finding to Bagley et al and other retrospective analysis from multiple institutes showing that NLR could be a good predictor of response to checkpoint inhibitors And a cutoff of NLR higher than 5.1 was associated with statistically significant better PFS and a trend towards a better OS.

The role of ALBI and IGF-CTP score in refining prognostication of HCC.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16659-e16659
Author(s):  
Sunyoung S. Lee ◽  
Yehia I. Mohamed ◽  
Aliya Qayyum ◽  
Manal Hassan ◽  
Lianchun Xiao ◽  
...  
Keyword(s):  
Overall Survival ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Survival Prediction ◽  
Score System ◽  
Risk Of Death ◽  
U Statistics ◽  
Cox Proportional Hazards Models ◽  
Ctp Score

e16659 Background: Child-Turcotte-Pugh (CTP) score is widely used in the assessment of prognosis of HCC and CTP-A is the standard criterion for active therapy and clinical trials entry. Recently, ALBI and insulin-like growth factor-1 (IGF)-CTP scores have been reported to improve survival prediction over CTP score. However, comparative studies to compare both scores and to integrate IGF into Albi score are lacking. Methods: After institutional board approval, data and samples were prospectively collected. 299 HCC patients who had data to generate both IGF-CPG and Albi index were used. The ALBI index, and IGF score were calculated, Cox proportional hazards models were fitted to evaluation the association between overall survival (OS) and CTP, IGF-CTP, Albi and IGF, albumin, bilirubin. Harrell’s Concordance index (C-index) was calculated to evaluate the ability of the three score system to predict overall survival. And the U-statistics was used to compare the performance of prediction of OS between the score system. Results: OS association with CTP, IGF-CTP and Albi was performed (Table). IGF-CTP B was associated with a higher risk of death than A (HR = 1.6087, 95% CI: 1.2039, 2.1497, p = 0.0013), ALBI grade 2 was also associated with a higher risk of death than 1 (HR = 2.2817, 95% CI: 1.7255, 3.0172, p < 0.0001). IGF-1(analyzed as categorical variable) was independently associated with OS after adjusting for the effects of ALBI grade. Which showed IGF-1 ≤26 was significantly associated with poor OS, P = 0.001. Conclusions: Although ALBI grade and IGF-CTP score in this analysis had similar prognostic values in most cases, their benefits might be heterogenous in some specific conditions. We looked into corporation of IGF-1 into ALBI grade, IGF score with cutoff ≤26 which clearly refined OS prediction and better OS stratification of ALBI-grade.

scholarly journals Serum gamma-glutamyltransferase and the overall survival of metastatic pancreatic cancer

2019 ◽  
Author(s):  
Yuanyuan Xiao ◽  
Haijun Yang ◽  
Jian Lu ◽  
Dehui Li ◽  
Chuanzhi Xu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Ductal Adenocarcinoma ◽  
Gamma Glutamyltransferase ◽  
Cancer Occurrence ◽  
Cox Proportional Hazards Models ◽  
Adequate Evaluation ◽  
Underlying Mechanisms

Abstract Background: Accumulating evidence suggests that Gamma-glutamyltransferase (GGT) may be involved in cancer occurrence and progression. However, the prognostic role of serum GGT in pancreatic cancer (PC) survival lacks adequate evaluation. In this study, we aimed to analyze the association between serum GGT measured at diagnosis and overall survival (OS) in patients with metastatic PC. Methods: We identified 320 patients with histopathologically confirmed metastatic pancreatic ductal adenocarcinoma (PDAC) diagnosed during 2015 and 2016 at a specialized cancer hospital in southwestern China. Univariate and multivariate Cox proportional-hazards models were used to determine associations between serum GGT and OS in metastatic PDAC. Results: Controlled for possible confounding factors, serum GGT was significantly associated with OS: serum GGT >48 U/L yielded a hazard ratio of 1.53 (95%CI: 1.19-1.97) for mortality risk. A significant dose-response association between serum GGT and OS was also observed. Subgroup analysis showed a possible interaction between GGT and blood glucose level. Conclusion: Serum GGT could be a potential indicator of survival in metastatic PDAC patients. Underlying mechanisms for this association should be investigated.

Sign in / Sign up

Export Citation Format

Share Document