scholarly journals Identification of Gene Markers for Survival Prediction of Lung Adenocarcinoma Patients Based on Integrated Multibody Data Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Yuwang Bao ◽  
Jianxiong Luo ◽  
Tianxing Yu ◽  
Yang Liu ◽  
Xiaohua Li ◽  
...  
Keyword(s):  
High Risk ◽  
Lung Adenocarcinoma ◽  
Risk Group ◽  
Clinical Information ◽  
High Risk Group ◽  
Cox Proportional Hazard Model ◽  
Proportional Hazard ◽  
Proportional Hazard Model ◽  
Cox Proportional Hazard ◽  
Information Group

We constructed a prognostic-related risk prediction for patients with lung adenocarcinoma by integrating multiple omics information of lung adenocarcinoma clinical information group and genome and transcriptome. Blood samples and cancer and paracancerous lung tissue samples were collected from 480 patients with lung adenocarcinoma. DNA and RNA sequencing was performed on DNA samples and RNA samples. The first follow-up was carried out 3 months after discharge. Clinical information of patients including age, gender, smoking history, and TNM stage was collected. The Cox proportional hazard model evaluated more than 600 potential SNPs related to the prognosis of lung adenocarcinoma. After LASSO analysis, we obtained 4 SNPs related to the prognosis of lung adenocarcinoma (including rs1059292, rs995343, rs2013335, and rs8078328). Through the Cox proportional hazard model, 260 candidate genes related to the prognosis of lung adenocarcinoma were evaluated. After subsequent analysis, 3 genes related to the prognosis of lung adenocarcinoma (LDHA, SDHC, and TYMS) were obtained. All survived patients were spilt into a high-risk group ( n = 170 ) and a low-risk group ( n = 170 ) according to 4 SNPs and 3 genes related to the prognosis of lung adenocarcinoma. The overall survival rate of patients in the high-risk group was lower than that in the low-risk group. The prognostic risk prediction index constructed by combining clinical information group and genomic and transcriptome characteristics of multiomics information can effectively distinguish the prognosis of patients with lung adenocarcinoma, which will provide effective support for the precise treatment of patients with lung adenocarcinoma.

Incorporating molecular markers in standard prognostic models for DLBCL patients using real-world data.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19251-e19251
Author(s):  
Shivam Mathura ◽  
Vicki Kay Fung ◽  
Keshava Dilwali ◽  
Ashwin Subramanian Lakshmanan
Keyword(s):  
Monoclonal Antibody ◽  
Molecular Markers ◽  
Risk Group ◽  
Risk Groups ◽  
Cox Proportional Hazard Model ◽  
Proportional Hazard ◽  
Proportional Hazard Model ◽  
Real World Data ◽  
Cox Proportional Hazard ◽  
The Relationship

e19251 Background: NCCN-IPI is a prognostic scoring system that outperforms other risk classification mechanisms in diffuse large B-cell lymphoma (DLBCL) but does not consider the molecular profile of patients. We evaluated the predictive value of NCCN-IPI and clinically relevant molecular markers on the overall survival (OS) of patients with diagnosed DLBCL in real-world data (RWD). Methods: Patients diagnosed with DLBCL were identified in the COTA RWD population, and then subset to those with sufficient attributes to calculate NCCN-IPI at diagnosis (age, stage, LDH ratio, performance status, extranodal disease) and those who received a monoclonal antibody targeting CD20 (n = 383). This population was further filtered to patients tested for BCL-2, BCL-6, and C-MYC (n = 176). Disease characteristics were summarized using descriptive statistics and chi-square tests of independence were performed to assess the relationship between NCCN-IPI Risk-Group and molecular marker results. A Cox proportional hazard model was used to identify prognostic features of OS. Results: There were statistically significant relationships between NCCN-IPI Risk-Group and both BCL-2 (p = 0.007) and C-MYC (p < 0.001) after Bonferroni correction for the number of molecular markers tested. A Cox proportional hazard model with the three molecular markers as covariates revealed a statistically significant correlation between the presence of C-MYC alteration and decreased OS (HR = 2.02, CI: 1.24-3.32, p = 0.005). However, when NCCN-IPI Risk-Group was added as a covariate, the relationship between C-MYC and OS was no longer significant. The hazard ratios associated with high-intermediate and high risk groups were larger than that of the low-intermediate group. All three of these risk groups were statistically significant in the model (p < 0.038). Conclusions: The inclusion of molecular markers to the NCCN-IPI prognostic model did not increase predictive power in this RWD cohort. We validated the NCCN-IPI model and found it to be a robust tool for classifying risk and estimating OS in patients who have received a CD20 monoclonal antibody. A larger sample size would increase power to further explore the impact of molecular markers on overall survival. [Table: see text]

scholarly journals Molecular-Based Score Inspired on Metabolic Signature Improves Prognostic Stratification for Myelodysplastic Syndrome

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4257-4257
Author(s):  
Juan L Coelho-Silva ◽  
Douglas R. A. Silveira ◽  
Diego A Pereira-Martins ◽  
César Alexander Ortiz Rojas ◽  
Antonio R. Lucena-Araujo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
High Risk ◽  
Cox Proportional Hazard Model ◽  
Proportional Hazard ◽  
Proportional Hazard Model ◽  
Cox Proportional Hazard ◽  
C Statistic ◽  
Cd34 Cells

Background : The recent efforts to uncover the molecular heterogeneity of myelodysplastic syndromes (MDS), mainly by new sequencing technologies, allow the comprehensive identification of driver mutations and/or altered gene expression recurrently found in a recognizable fraction of patients. Ongoing efforts are being made to clarify the impact of molecular changes on clinical phenotype and prognosis, as well as their role in the pathogenesis of MDS. Refining risk stratification allows the proposition of risk-adapted therapy and may shed light in biology of MDS. Aims: Based on the gene expression of selected metabolic targets, we aimed to design a score system that improves MDS overall survival prediction. Patients and methods: Clinical, mutations and transcriptomic data from CD34+ cells from 159 MDS patients and 17 healthy volunteers freely available at Gene Expression Omnibus (GEO/NCBI: GSE58831) were used in the present work. Forty-one genes related to metabolic processes, previously demonstrated as deregulated among diverse neoplastic conditions, were ranked and asked for differential expression and prognostic impact. Each gene was dichotomized according to Receiving-Operating Curve (ROC) and Cox Proportional-Hazard Model was used for multivariate analysis using gender, age and IPSS-R as cofounders. Genes independently associated with overall survival (OS) were selected to compose the Molecular-Based Score (MBS) and integer weight of each one was defined according Hazard Ratio (HR). Survival curves were constructed using Kaplan-Meyer method and compared with Log-Rank Test. ROC c-statistic was used to measure the predictive function of MBS. Prediction accuracy of MBS was cross-validated by a nonparametric bootstrap procedure with 1,000 resamplings of the original cohort allowing replacement and also estimated their respective 95% confidence interval (95% CI) computing the bias-corrected and accelerated bootstrap interval. Results: Among selected genes, 18 were differentially expressed between CD34+ cells from MDS and healthy volunteers. Fifteen genes predict OS in univariate analysis, of which ACLY (HR: 0.48; 95%CI: 0.24 - 0.96; P=0.04), ANPEP (HR: 2.16; 95%CI: 1.08 - 4.31; P=0.02), PANK1 (HR: 0.43; 95%CI: 0.19 - 0.98; P=0.04), PKM (HR: 2.01; 95%CI: 1.02 - 3.93; P=0.04) and SLC25A5 (HR: 0.52; 95%CI: 0.27 - 0.99; P=0.05) were independently associated with OS. Higher expression of ANPEP and PKM, as well as lower expression of ACLY, PANK1 and SLC25A5 were considered to integer high risk being attributed weight 2 for each condition. MBS varied from 0 to 10 (median=2) and was calculated as: MBS Low-Risk =0 (MBS-LR; n=28); MBS Intermediate-Risk=2 and 4 (MBS-IR; n=90) and High-Risk: ≥6 (MBS-HR; n=48). The modeled MBS showed a ROC c-statistic of 0.699 (95%CI: 0.603 - 0.794) and HR=3.05 (95%CI: 1.81 - 5.05; P<0.001) and efficiently identified patients with different risk: MBS-LR (3-year OS: 100%; median time [MT]: not reached); MBS-IR (3-year OS: 66% [95%CI: 53% - 83%]; MT: 52.2 months [95%CI: 34.2 - 71.5]) and MBS-HR (3-year OS: 32% [95%CI: 17% - 61%]; MT: 23.5 months [95%CI: 11.6 - 35.4]). Using Cox Proportional Hazard Model for multivariate analysis, the proposed MBS (HR:2.5 [95%CI: 1.2-4.96]; P=0.008) was independently associated with OS using gender (HR:0.48 [95%CI: 0.21-1.06]; P=0.07), age (HR:1.03 [95%CI: 1.001-1.07]; P=0.02) and IPSS-R (HR:0.98 [95%CI: 0.69-1.36]; P=0.88) as confounders. The bootstrap resampling procedure validated the MBS and demonstrated the stability of its prediction (3-year OS for MBS-LR: 100% [95%CI: 100-100%]; MBS-IR: 66% [95%CI: 49-80%]; MBS-HR: 32% [95%CI: 13-54%]; P<0.001). Conclusions: The proposed Molecular-Based Score (MBS) independently predict OS with superior efficacy in comparison to the most clinically relevant prognostic factors, and reinforce the therapeutic opportunity of metabolic processes in MDS. Figure Disclosures No relevant conflicts of interest to declare.

Prostatectomy in men with clinically positive lymph nodes.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 327-327
Author(s):  
Fady Ghali ◽  
Stephen Ryan ◽  
Moritz Hansen ◽  
Matthew Hayn ◽  
Jesse Sammon ◽  
...  
Keyword(s):  
High Risk ◽  
Lymph Nodes ◽  
Systemic Therapy ◽  
Clinical Staging ◽  
Cox Proportional Hazard Model ◽  
Proportional Hazard ◽  
Proportional Hazard Model ◽  
Cox Proportional Hazard ◽  
Biopsy Gleason Score ◽  
Positive Lymph Nodes

327 Background: A prostate cancer (PCa) patient with non-metastatic but clinical positive lymph nodes (cN+) represents a difficult clinical scenario. We compared OS after RP in cN- (High Risk), cN+/pN- (Discordant), and cN+/pN+ (Concordant). Methods: The National Cancer Database was queried for all PCa patients from 2004-2013. Inclusion criteria were known age and PSA at diagnosis, biopsy Gleason score, TNM staging (cT1-3B, cN0/1, M0/X), margin, nodal status and primary treatment modality. cN+ was separated into two cohorts: pN- (Discordant) and pN+ (Concordant). RPs for High Risk PCa (cT3a/b or GS ≥ 8 or PSA > 20) with cN- was used as a comparison. OS was analyzed with Kaplan Meier (KMA) and Cox proportional hazard model combing demographic, clinical, and pathological factors. Results: 4944 cN+ men were identified (21.7% RP, 27.5% systemic therapy only). 794 RPs had completed records. Discordant and Concordant represented 18.8% and 81.2% with median follow-up 48 and 48.9 months, and 13 and 97 deaths, respectively. KMA pairwise OS of High Risk (n=35, 502) verses Discordant was not significant (p=0.28) but was significant verses Concordant (p < 0.001). There was no difference in OS on KMA between Discordant and Concordant (p=0.11). OS on Cox proportional hazard model, High Risk and Discordant had no observable difference (p=1.22). Concordant pathology had much worsened OS (HR 1.829, p < 0.001), as well as Medicaid/Medicare patients (HR 1.344, p < 0.001), biopsy Gleason score ≥ 8 (HR 1.350, p=0.0019), pathologic T stage (pT3a HR 1.567, pT3b 2.396, p < 0.001), and positive surgical margin (HR 1.257, p < 0.001). Conclusions: In a large cohort of nonmetastatic PCa patients with cN+ disease, > 27% were treated with systemic therapy based on clinical staging, but 18.8% of cN+ RPs were incorrectly staged. There was no difference in OS between cN- High Risk patients and pathologic Discordant (cN+/pN-) men, and the much worse OS in men with pN+. Study is needed for more accurate clinical staging tools to identify the pathologically discordant population.

Validation of a five reagent immunohistochemistry assay for prognostication of estrogen-receptor expressing breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10081-10081
Author(s):  
D. T. Ross ◽  
A. R. Frost ◽  
R. Beck ◽  
R. S. Seitz ◽  
B. Z. Ring
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
High Risk ◽  
Cox Proportional Hazard Model ◽  
Proportional Hazard ◽  
Breast Cancer Patients ◽  
Proportional Hazard Model ◽  
Cox Proportional Hazard ◽  
Estrogen Receptor Positive ◽  
Risk Patients

10081 Background: We have previously reported the translation of gene expression data into a five reagent polyclonal antibody immunohistochemistry assay targeting p53, SLC7A5, NDRG1, HTF9C, and CEACAM5 whose staining results are combined using a Cox proportional hazard model for prognostication of estrogen receptor expressing breast cancer. Monoclonal antibodies targeting these genes have now been obtained and or produced. Methods: Paraffin blocks from 229 patients seen at the University of Alabama at Birmingham Clinical Cancer Center were assembled into tissue arrays and clinical follow-up data was collected by chart review. Immunohistochemical stains were performed and cases scored as positive or negative with the five monoclonal antibody assay. In order to further test the assays predictive value for assessing outcome, the prospectively defined Cox proportional hazard model and high, moderate, and low risk cutoffs were applied to the staining results on the estrogen receptor positive (ER+) patients for whom a assessment of death due to disease (DOD) and staining results for all five biomarkers were available. Results: The Kaplan-Meier estimates of outcome confirmed that the Cox model distinguished ER+ patients with poor outcomes. The five antisera algorithm identified high risk patients with a five year estimate of DOD of 41% compared to 20% for moderate and 9% for good (p=0.006) (79 patients total). In ER+ node negative patients the model identified high risk patients with a five year estimate of DOD of 50% compared to 18% for moderate and 5% for good (p=0.01) (40 patients total). The prognosticator was independent of age, pathological stage, and tumor size. Conclusions: A panel of five antibodies can significantly improve upon traditional prognosticators in predicting outcome for estrogen receptor positive breast cancer patients. This represents the third independent validation study performed on cohorts from different institutions. Retrospective studies on clinical trial cohorts and prospective studies should be performed to further establish the utility of this test in identifying early stage breast cancer patients at high risk for recurrence. [Table: see text]

scholarly journals A Study of Factors Affecting the Length of Hospital Stay of COVID-19 Patients by Cox-Proportional Hazard Model in a South Indian Tertiary Care Hospital

2021 ◽  
Vol 12 ◽  
pp. 215013272110002
Author(s):  
Gayathri Thiruvengadam ◽  
Marappa Lakshmi ◽  
Ravanan Ramanujam
Keyword(s):  
Hospital Stay ◽  
Tertiary Care ◽  
Length Of Hospital Stay ◽  
Hazard Model ◽  
Cox Proportional Hazard Model ◽  
Care Hospital ◽  
Proportional Hazard ◽  
Proportional Hazard Model ◽  
Cox Proportional Hazard ◽  
South Indian

Background: The objective of the study was to identify the factors that alter the length of hospital stay of COVID-19 patients so we have an estimate of the duration of hospitalization of patients. To achieve this, we used a time to event analysis to arrive at factors that could alter the length of hospital stay, aiding in planning additional beds for any future rise in cases. Methods: Information about COVID-19 patients was collected between June and August 2020. The response variable was the time from admission to discharge of patients. Cox proportional hazard model was used to identify the factors that were associated with the length of hospital stay. Results: A total of 730 COVID-19 patients were included, of which 675 (92.5%) recovered and 55 (7.5%) were considered to be right-censored, that is, the patient died or was discharged against medical advice. The median length of hospital stay of COVID-19 patients who were hospitalized was found to be 7 days by the Kaplan Meier curve. The covariates that prolonged the length of hospital stay were found to be abnormalities in oxygen saturation (HR = 0.446, P < .001), neutrophil-lymphocyte ratio (HR = 0.742, P = .003), levels of D-dimer (HR = 0.60, P = .002), lactate dehydrogenase (HR = 0.717, P = .002), and ferritin (HR = 0.763, P = .037). Also, patients who had more than 2 chronic diseases had a significantly longer length of stay (HR = 0.586, P = .008) compared to those with no comorbidities. Conclusion: Factors that are associated with prolonged length of hospital stay of patients need to be considered in planning bed strength on a contingency basis.

scholarly journals POS1329 A COHORT STUDY ON THE RISK OF DEVELOPING OBSTRUCTIVE SLEEP APNEA, TEMPOROMANDIBULAR JOINT DISORDERS AND CRANIOFACIAL DEFORMITIES IN PATIENTS WITH JUVENILE IDIOPATHIC ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 947.1-947
Author(s):  
K. S. K. MA ◽  
L. T. Wang
Keyword(s):  
Obstructive Sleep Apnea ◽  
Cohort Study ◽  
Juvenile Idiopathic Arthritis ◽  
Cox Proportional Hazard Model ◽  
Proportional Hazard ◽  
Proportional Hazard Model ◽  
Cox Proportional Hazard ◽  
Obstructive Sleep ◽  
Subgroup Analyses ◽  
Underlying Mechanisms

Background:Juvenile Idiopathic Arthritis (JIA), an autoimmune disease, has been proposed to be comorbid with obstructive sleep apnea (OSA).Objectives:We aimed at identifying the relationship between JIA and OSA.Methods:We performed a cohort study including JIA and OSA patients from 1999 to 2013. A total of 2791 patients diagnosed with OSA after JIA onset were recruited, which 11,164 eligible individuals without JIA history were selected as matched-controls. A Cox proportional hazard model was developed to estimate the risk of OSA in JIA patients. A cumulative probability model was adopted to assess the time-dependent effect of JIA on OSA development, implying the casual link of the association. To identify whether JIA patients have higher risks for developing temporomandibular joint (TMJ) disorders, craniofacial anomalies and deformities than non-JIA individuals, subgroup analyses was conducted. Finally, Ingenuity Systems Pathway Analysis (IPA) was conducted to identify underlying mechanisms of the above disease correlation among peripheral blood mononuclear cells (PBMCs) from rheumatic factor (RF)-positive and RF-negative JIA patients, and subcutaneous fat tissues from OSA patients, using p-value visualization for RNA-seq analyses.Results:The Cox proportional hazard model showed that JIA patients were more likely to have OSA than non-JIA individuals (adjusted hazard ratio =1.949, 95% CI =1.264–3.005). The incidence of developing OSA was particularly high among patients who developed JIA aged 18-30 years old (aHR= 2.034, 95% CI=1.305-3.169) and males (aHR=1.82, 95% CI=1.121-2.954). The risk of developing OSA increased within 0-36 months (aHR = 2.216, 95% CI = 1.001 – 4.907) and over 60 months (aHR = 2.558, 95% CI = 1.346 – 4.860) of follow-up duration after JIA onset. Subgroup analyses showed that JIA patients were more likely to have TMJ disorders (relative risk = 2.047, 95% CI = 1.446-2.898) and to receive treatment for craniofacial deformities (RR = 1.722, 95% CI = 1.38-2.148) than non-JIA controls. IPA analyses suggested that the underlying mechanisms involved activation of antigen presentation pathway followed by antigen presentation to CD4+ and CD8+ T lymphocytes, as well as B cell development.Conclusion:Our findings identified high risks of developing OSA, TMJ disorders, and craniofacial deformities following JIA onset, which the underlying mechanisms may involve both cellular and humoral immunity.Disclosure of Interests:None declared

scholarly journals Immunogenomic Gene Signature of Cell-Death Associated Genes with Prognostic Implications in Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 155
Author(s):  
Pankaj Ahluwalia ◽  
Meenakshi Ahluwalia ◽  
Ashis K. Mondal ◽  
Nikhil Sahajpal ◽  
Vamsi Kota ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
High Risk ◽  
Lung Adenocarcinoma ◽  
Risk Group ◽  
High Risk Group ◽  
Free Survival ◽  
Cell Death Pathways

Lung cancer is one of the leading causes of death worldwide. Cell death pathways such as autophagy, apoptosis, and necrosis can provide useful clinical and immunological insights that can assist in the design of personalized therapeutics. In this study, variations in the expression of genes involved in cell death pathways and resulting infiltration of immune cells were explored in lung adenocarcinoma (The Cancer Genome Atlas: TCGA, lung adenocarcinoma (LUAD), 510 patients). Firstly, genes involved in autophagy (n = 34 genes), apoptosis (n = 66 genes), and necrosis (n = 32 genes) were analyzed to assess the prognostic significance in lung cancer. The significant genes were used to develop the cell death index (CDI) of 21 genes which clustered patients based on high risk (high CDI) and low risk (low CDI). The survival analysis using the Kaplan–Meier curve differentiated patients based on overall survival (40.4 months vs. 76.2 months), progression-free survival (26.2 months vs. 48.6 months), and disease-free survival (62.2 months vs. 158.2 months) (Log-rank test, p < 0.01). Cox proportional hazard model significantly associated patients in high CDI group with a higher risk of mortality (Hazard Ratio: H.R 1.75, 95% CI: 1.28–2.45, p < 0.001). Differential gene expression analysis using principal component analysis (PCA) identified genes with the highest fold change forming distinct clusters. To analyze the immune parameters in two risk groups, cytokines expression (n = 265 genes) analysis revealed the highest association of IL-15RA and IL 15 (> 1.5-fold, p < 0.01) with the high-risk group. The microenvironment cell-population (MCP)-counter algorithm identified the higher infiltration of CD8+ T cells, macrophages, and lower infiltration of neutrophils with the high-risk group. Interestingly, this group also showed a higher expression of immune checkpoint molecules CD-274 (PD-L1), CTLA-4, and T cell exhaustion genes (HAVCR2, TIGIT, LAG3, PDCD1, CXCL13, and LYN) (p < 0.01). Furthermore, functional enrichment analysis identified significant perturbations in immune pathways in the higher risk group. This study highlights the presence of an immunocompromised microenvironment indicated by the higher infiltration of cytotoxic T cells along with the presence of checkpoint molecules and T cell exhaustion genes. These patients at higher risk might be more suitable to benefit from PD-L1 blockade or other checkpoint blockade immunotherapies.

Exploration of Tumor Mutation Burden Combined with Immune Infiltrates in the Prognosis of Lung Adenocarcinoma

2021 ◽  
Author(s):  
Zhenyu Zhao ◽  
Boxue He ◽  
Qidong Cai ◽  
Pengfei Zhang ◽  
Xiong Peng ◽  
...  
Keyword(s):  
High Risk ◽  
Lung Adenocarcinoma ◽  
Clinical Application ◽  
Risk Group ◽  
High Risk Group ◽  
Immune Microenvironment ◽  
Tumor Mutation Burden ◽  
Immune Signature ◽  
Immune Infiltration ◽  
Mutation Burden

Abstract Background: Lung adenocarcinoma (LUAD) accounts for a majority of cancer-related deaths worldwide annually. A recent study shows that immunotherapy is an effective method of LUAD treatment, and tumor mutation burden (TMB) was associated with the immune microenvironment and affected the immunotherapy. Exploration of the gene signature associated with tumor mutation burden and immune infiltrates in predicting prognosis in lung adenocarcinoma in this study, we explored the correlation of TMB with immune infiltration and prognosis in LUAD.Materials and Methods: In this study, we firstly got mutation data and LUAD RNA-Seq data of the LUAD from The Cancer Genome Atlas (TCGA), and according to the TMB we divided the patients into high/low-TMB levels groups. The gene ontology (GO) pathway enrichment analysis and KOBAS-Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis were utilized to explore the molecular function of the differentially expressed genes (DEGs) between the two groups. The function enrichment analyses of DEGs were related to the immune pathways. Then, the ESTIMATE algorithm, CIBERSORT, and ssGSEA analysis were utilized to identify the relationship between TMB subgroups and immune infiltration. According to the results, Venn analysis was utilized to select the immune-related genes in DEGs. Univariate and Lasso Cox proportional hazards regression analyses were performed to construct the signature which positively associated with the immune infiltration and affected the survival. Finally, we verified the correlation between the signature and immune infiltration. Result: The exploration of the immune infiltration suggested that high-TMB subgroups positively associated with the high level of immune infiltration in LUAD patients. According to the TMB-related immune signature, the patients were divided into High/Low-risk groups, and the high-risk group was positively associated with poor prognostic. The results of the PCA analysis confirmed the validity of the signature. We also verified the effectiveness of the signature in GSE30219 and GSE72094 datasets. The ROC curves and C-index suggested the good clinical application of the TMB-related immune signature in LUAD prognosis. Another result suggested that the patients of the high-risk group were positively associated with higher TMB levels, PD-L1expression, and immune infiltration levels.Conclusion: In conclusion, our signature provides potential biomarkers for studying aspects of the TMB in LUAD such as TMB affected immune microenvironment and prognosis. This signature may provide some biomarkers which could improve the biomarkers of PD-L1 immunotherapy response and were inverted for the clinical application of the TMB in LUAD. LUAD male patients with higher TMB-levels and risk scores may benefit from immunotherapy. The high-risk patients along with higher PD-L1 expression of the signature may suitable for immunotherapy and improve their survival by detecting the TMB of LUAD.

scholarly journals Proton pump inhibitor is a risk factor for recurrence of common bile duct stones after endoscopic sphincterotomy – propensity score matching analysis

2017 ◽  
Vol 05 (04) ◽  
pp. E291-E296
Author(s):  
Nobuhiko Fukuba ◽  
Shunji Ishihara ◽  
Hiroki Sonoyama ◽  
Noritsugu Yamashita ◽  
Masahito Aimi ◽  
...  
Keyword(s):  
Bile Duct ◽  
Propensity Score ◽  
Propensity Score Matching ◽  
Common Bile Duct Stones ◽  
Cox Proportional Hazard Model ◽  
Proportional Hazard ◽  
Bile Duct Stones ◽  
Proportional Hazard Model ◽  
Propensity Score Matching Analysis ◽  
Cox Proportional Hazard

Abstract Background and study aims Recurrence of common bile duct stones (CBDS) in patients treated with endoscopic sphincterotomy (ES) can lead to deterioration in their quality of life. Although the pathology and related factors are unclear, we speculated that proton pump inhibiter (PPI) administration increases the risk of CBDS recurrence by altering the bacterial mixture in the bile duct. Patients and methods The primary endpoint of this retrospective study was recurrence-free period. Several independent variables considered to have a relationship with CBDS recurrence including PPI use were analyzed using a COX proportional hazard model, with potential risk factors then evaluated by propensity score matching analysis. Results A total of 219 patients were analyzed, with CBDS recurrence found in 44. Analysis of variables using a COX proportional hazard model demonstrated that use of PPIs and ursodeoxycholic acid (UDCA), as well as the presence of periampullary diverticula (PD) each had a hazard ratio (HR) value greater than 1 (HR 2.2, P = 0.007; HR 2.0, P = 0.02; HR 1.9, P = 0.07; respectively). Furthermore, propensity score matching analysis revealed that the mean recurrence-free period in the oral PPI cohort was significantly shorter as compared with the non-PPI cohort (1613 vs. 2587 days, P = 0.014). In contrast, neither UDCA administration nor PD presence was found to be a significant factor in that analysis (1557 vs. 1654 days, P = 0.508; 1169 vs. 2011 days, P = 0.121; respectively). Conclusion Our results showed that oral PPI administration is a risk factor for CBDS recurrence in patients who undergo ES.

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