scholarly journals OPN Polymorphism Is Related to the Chemotherapy Response and Prognosis in Advanced NSCLC

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Yanzhang Hao ◽  
Jianwei Liu ◽  
Ping Wang ◽  
Feng Wang ◽  
Zeshun Yu ◽  
...  
Keyword(s):  
Gene Polymorphism ◽  
Gene Polymorphisms ◽  
Proportional Hazards ◽  
Advanced Nsclc ◽  
Cox Proportional Hazards ◽  
Chemotherapy Response ◽  
Proportional Hazards Regression ◽  
Platinum Based Chemotherapy ◽  
Response To Chemotherapy ◽  
Nsclc Patients

Background.Osteopontin (OPN) is associated with prognosis of patients with non-small-cell lung cancer (NSCLC). However, little is known about the association between OPN gene polymorphism and the chemotherapy response in NSCLC patients.Methods.A total of 497 patients with inoperable advanced stage of NSCLC (stages III B and IV NSCLC) were enrolled. All patients had received platinum-based chemotherapy. OPN gene polymorphisms at 156 GG/G, 443 C/T, and −66T/G were determined.Results.The genotypes and allele frequency of −443C>T were significantly different between the responders and nonresponders. Responders had a markedly higher frequency of −443TT genotype than responders (40.71% versus 19.09%,P<0.001). With CC as reference, the TT genotype carriers had a higher chance to be well responders (adjustedOR=4.43, 95% CI: 2.60–7.53, adjustedP<0.001). The median overall survival time for patients with −443CC, −443CT, and −443TT genotype carriers was significantly different. Multivariate Cox proportional hazards regression models showed that OPN −443C>T gene polymorphisms were closely correlated to poor NSCLC prognosis.Conclusion.OPN −443C>T gene polymorphism may be used as a molecular marker to predict the treatment response to chemotherapy in advanced NSCLC patients.

Association of low RKIP expression with poor prognosis in non-small cell lung cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3068-3068
Author(s):  
Lingbin Meng ◽  
Rui Ji ◽  
Damian A. Laber ◽  
Xuebo Yan ◽  
Xiaochun Xu
Keyword(s):  
Overall Survival ◽  
Tumor Size ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Tnm Stage ◽  
Erk Signaling ◽  
Small Cell Lung ◽  
Proportional Hazards Regression ◽  
Kaplan Meier ◽  
Nsclc Patients

3068 Background: Raf1 kinase inhibitor protein (RKIP) is able to bind Raf1 to inhibit Ras-Raf-MEK-ERK signaling, a major oncogenic pathway. It has been reported that reduced RKIP expression associates with poor prognosis in many cancers, including gastric adenocarcinoma, gliomas and bladder cancer. However, there are only several studies on its role in non-small cell lung cancer (NSCLC) and the conclusion is still controversial. Hence, we performed this study to assess the prognostic significance of RKIP in our NSCLC population. Methods: Between June 2017 and June 2020, 156 NSCLC patients treated at our hospital were included for the present study. None of the patients had received chemotherapy, radiotherapy or surgery before. Their tumor tissues and surrounding normal lung tissues were collected for immunostain and western blot analysis of RKIP expression and ERK signaling. We collected information about gender, age, histological differentiation, tumor size, TNM stage, and lymph node status. Survival curves were analyzed using the Kaplan-Meier method. Cox proportional hazards model was used to determine the prognostic value of various variables in a univariate and multivariate setting. Results: Immunostain and western blot results showed a lower RKIP expression and a higher p-ERK level in cancer tissues compared with the surrounding normal tissues. A reduced RKIP expression with high level of p-ERK was also observed in TNM stages III and IV as compared with I and II. Pearson's chi-squared test confirmed low RKIP expression associated with poorer TNM stage ( p< 0.001) and N-stage ( p< 0.05). No significant correlation was observed between RKIP expression level and gender, age, histological type or tumor size. Kaplan-Meier survival analysis revealed that patients with low RKIP expression had significantly worse overall survival than patients with high RKIP expression ( p= 0.019, log-rank). This conclusion was consistent in the stage I&II patients ( p= 0.011, log-rank) but not in the stage III&IV patients ( p= 0.711, log-rank). Univariate Cox proportional hazards regression analysis indicated Tumor size, TNM stage and RKIP expression significantly affected overall survival of the NSCLC patients. Multivariate Cox proportional hazards regression analysis confirmed RKIP expression remained a significant predictor of survival after correcting for the effects of Tumor size and TNM stage (hazard ratio = 1.730, 95% confidence interval = 1.017 – 2.942, p = 0.043). Conclusions: In this study, low RKIP expression was a poor prognostic indicator in NSCLC as it significantly correlated with poorer TNM stage, N-status, and overall survival. Our findings suggest that by inhibiting Ras-Raf-MEK-ERK pathway RKIP may play an anti-tumor role in NSCLC.

Association of liver metastases (LM) with survival in NSCLC patients treated with durvalumab (D) in two independent clinical trials.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3038-3038 ◽  
Author(s):  
Luis G. Paz-Ares ◽  
Kui Shen ◽  
Brandon W. Higgs ◽  
Chris Morehouse ◽  
Naiyer A. Rizvi ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Proportional Hazards ◽  
Advanced Nsclc ◽  
Independent Predictor ◽  
Phase 1 ◽  
Tumor Stage ◽  
Cox Proportional Hazards ◽  
Clinical Factors ◽  
Nsclc Patients ◽  
Clinical Trial Information

3038 Background: Immunotherapies have improved survival in NSCLC but not all pts benefit. Besides baseline PDL1 expression, routinely measured clinical factors may predict clinical outcomes in immunotherapy trials. LM are associated with poor prognosis in melanoma and bladder cancer pts treated with anti-PD1/L1, respectively. We examined correlation between pretreatment LM and survival in D-treated NSCLC pts. Methods: CP1108/NCT01693562 and ATLANTIC/NCT02087423 were nonrandomized phase 1/2 and 2 trials, respectively, of D 10 mg/kg Q2W in advanced NSCLC. As of Oct 24/Jun 3 2016, 304/265 primarily pretreated pts were enrolled in CP1108/ATLANTIC Cohort 2. Cox proportional hazards analysis was conducted, first among LM+/− pts, then LM+/− and PDL1 high/low pts. Both models accounted for tumor stage, ECOG/WHO PS, histology, sex, age, smoking and PDL1 status. PDL1 high was defined as ≥25% tumor cells immunostained for PDL1 at any intensity. Results: LM absence was a positive independent predictor of OS and PFS in both trials. LM− and PDL1 high or low pts had improved OS and PFS vs PDL1 low/LM+; PDL1 high/LM+ pts had improved PFS vs PDL1 low/LM+. An independent tumor kinetic model indicated LM as a predictive covariate of rapid tumor growth in D-treated pts. Conclusions: LM are associated with shorter survival in D-treated NSCLC pts in 2 trials irrespective of PDL1 status. Clinical trial information: NCT02087423 and NCT01693562. [Table: see text]

Prediction models for platinum-based chemotherapy response and toxicity in advanced NSCLC patients

2016 ◽  
Vol 377 (1) ◽  
pp. 65-73 ◽  
Author(s):  
Ji-Ye Yin ◽  
Xi Li ◽  
Xiang-Ping Li ◽  
Ling Xiao ◽  
Wei Zheng ◽  
...  
Keyword(s):  
Prediction Models ◽  
Advanced Nsclc ◽  
Chemotherapy Response ◽  
Platinum Based Chemotherapy ◽  
Nsclc Patients

ERCC5 Is a Novel Biomarker of Ovarian Cancer Prognosis

2008 ◽  
Vol 26 (18) ◽  
pp. 2952-2958 ◽  
Author(s):  
Christine S. Walsh ◽  
Seishi Ogawa ◽  
Hisae Karahashi ◽  
Daniel R. Scoles ◽  
James C. Pavelka ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ovarian Cancer ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Cancer Prognosis ◽  
Whole Genome ◽  
Repair Pathway ◽  
Platinum Based Chemotherapy ◽  
Response To Chemotherapy ◽  
Ovarian Cancer Prognosis

Purpose To identify a biomarker of ovarian cancer response to chemotherapy. Patients and Methods Study participants had epithelial ovarian cancer treated with surgery followed by platinum-based chemotherapy. DNA and RNA were isolated from frozen tumors and normal DNA was isolated from matched peripheral blood. A whole-genome loss of heterozygosity (LOH) analysis was performed using a high-density oligonucleotide array. Candidate genomic areas that predicted enhanced response to chemotherapy were identified with Cox proportional hazards methods. Gene expression analyses were performed through microarray experiments. Candidate genes were tested for independent effects on survival using Cox proportional hazards models, Kaplan-Meier survival curves, and the log-rank test. Results Using a whole-genome approach to study the molecular determinants of ovarian cancer response to platinum-based chemotherapy, we identified LOH of a 13q region to predict prolonged progression-free survival (PFS; hazard ratio, 0.23; P = .006). ERCC5 was identified as a candidate gene in this region because of its known function in the nucleotide excision repair pathway, the unique DNA repair pathway that removes platinum-DNA adducts. We found LOH of the ERCC5 gene locus and downregulation of ERCC5 gene expression to predict prolonged PFS. Integration of genomic and gene expression data shows a correlation between 13q LOH and ERCC5 gene downregulation. Conclusion ERCC5 is a novel biomarker of ovarian cancer prognosis and a potential therapeutic target of ovarian cancer response to platinum chemotherapy.

scholarly journals BMP-4 Genetic Variants and Protein Expression Are Associated with Platinum-Based Chemotherapy Response and Prognosis in NSCLC

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Sun Xian ◽  
Lang Jilu ◽  
Tian Zhennan ◽  
Zhou Yang ◽  
Hu Yang ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Advanced Nsclc ◽  
Nonsmall Cell Lung Cancer ◽  
Tissue Expression ◽  
Chemotherapy Response ◽  
Potential Predictor ◽  
Bone Morphogenic Proteins ◽  
Platinum Based Chemotherapy ◽  
Nsclc Patients

To explore the role of genetic polymorphisms of bone morphogenic proteins 4 (BMP-4) in the response to platinum-based chemotherapy and the clinical outcome in patients with advanced nonsmall cell lung cancer (NSCLC), 938 patients with stage III (A+B) or IV NSCLC were enrolled in this study. We found that the variant genotypes of 6007C > T polymorphisms significantly associated with the chemotherapy response. The 6007CC genotype carriers had a higher chance to be responder to chemotherapy (adjusted odd ratio = 2.77; 95% CI: 1.83–4.18; adjusted < 0.001). The 6007C > T polymorphisms and BMP-4 expression also affect the prognosis of NSCLC. Patients with high BMP-4 expression had a significantly higher chance to be resistant to chemotherapy than those with low BMP-4 expression (OR = 2.81; 95% CI: 1.23–6.44;P=0.01). The hazard ratio (HR) for 6007TT was 2.37 times higher than 6007CC (P=0.003). In summary, the 6007C > T polymorphism of BMP-4 gene and BMP-4 tissue expression may be used as potential predictor for the chemotherapy response and prognosis of advanced NSCLC.

PETCO2 gradient: a novel prognostic parameter in cardiopulmonary exercise testing

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
I.D Poveda Pinedo ◽  
I Marco Clement ◽  
O Gonzalez ◽  
I Ponz ◽  
A.M Iniesta ◽  
...  
Keyword(s):  
Exercise Testing ◽  
Proportional Hazards ◽  
Cardiopulmonary Exercise Testing ◽  
Cox Proportional Hazards ◽  
Prognostic Parameter ◽  
Cardiopulmonary Exercise ◽  
Proportional Hazards Regression ◽  
Kaplan Meier ◽  
Baseline Characteristics ◽  
The Difference

Abstract Background Previous parameters such as peak VO2, VE/VCO2 slope and OUES have been described to be prognostic in heart failure (HF). The aim of this study was to identify further prognostic factors of cardiopulmonary exercise testing (CPET) in HF patients. Methods A retrospective analysis of HF patients who underwent CPET from January to November 2019 in a single centre was performed. PETCO2 gradient was defined by the difference between final PETCO2 and baseline PETCO2. HF events were defined as decompensated HF requiring hospital admission or IV diuretics, or decompensated HF resulting in death. Results A total of 64 HF patients were assessed by CPET, HF events occurred in 8 (12.5%) patients. Baseline characteristics are shown in table 1. Patients having HF events had a negative PETCO2 gradient while patients not having events showed a positive PETCO2 gradient (−1.5 [IQR −4.8, 2.3] vs 3 [IQR 1, 5] mmHg; p=0.004). A multivariate Cox proportional-hazards regression analysis revealed that PETCO2 gradient was an independent predictor of HF events (HR 0.74, 95% CI [0.61–0.89]; p=0.002). Kaplan-Meier curves showed a significantly higher incidence of HF events in patients having negative gradients, p=0.002 (figure 1). Conclusion PETCO2 gradient was demonstrated to be a prognostic parameter of CPET in HF patients in our study. Patients having negative gradients had worse outcomes by having more HF events. Time to first event, decompensated heart Funding Acknowledgement Type of funding source: None

scholarly journals Associated characteristics and treatment outcomes of medication-related osteonecrosis of the jaw in patients receiving denosumab or zoledronic acid for bone metastases

2021 ◽  
Author(s):  
Hiroaki Ikesue ◽  
Moe Mouri ◽  
Hideaki Tomita ◽  
Masaki Hirabatake ◽  
Mai Ikemura ◽  
...  
Keyword(s):  
Zoledronic Acid ◽  
Bone Metastases ◽  
Tooth Extraction ◽  
Proportional Hazards ◽  
Osteonecrosis Of The Jaw ◽  
Cox Proportional Hazards ◽  
Patients With Cancer ◽  
Proportional Hazards Regression ◽  
Before And After ◽  
Denosumab Treatment

Abstract Purpose This study aimed to evaluate the association between clinical characteristics and development of medication-related osteonecrosis of the jaw (MRONJ) in patients who underwent dental examinations before the initiation of treatment with denosumab or zoledronic acid, which are bone-modifying agents (BMAs), for bone metastases. Additionally, the clinical outcomes of patients who developed MRONJ were evaluated along with the time to resolution of MRONJ. Methods The medical charts of patients with cancer who received denosumab or zoledronic acid for bone metastases between January 2012 and September 2016 were retrospectively reviewed. Patients were excluded if they did not undergo a dental examination at baseline. Results Among the 374 included patients, 34 (9.1%) developed MRONJ. The incidence of MRONJ was significantly higher in the denosumab group than in the zoledronic acid (27/215 [12.6%] vs 7/159 [4.4%], P = 0.006) group. Multivariate Cox proportional hazards regression analysis revealed that denosumab treatment, older age, and tooth extraction before and after starting BMA treatments were significantly associated with developing MRONJ. The time to resolution of MRONJ was significantly shorter for patients who received denosumab (median 26.8 months) than for those who received zoledronic acid (median not reached; P = 0.024). Conclusion The results of this study suggest that treatment with denosumab, age > 65 years, and tooth extraction before and after starting BMA treatments are significantly associated with developing MRONJ in patients undergoing treatment for bone metastases. However, MRONJ caused by denosumab resolves faster than that caused by zoledronic acid.

scholarly journals Sex-Specific Associations between Blood Pressure and Risk of Atrial Fibrillation Subtypes in the Tromsø Study

2021 ◽  
Vol 10 (7) ◽  
pp. 1514
Author(s):  
Hilde Espnes ◽  
Jocasta Ball ◽  
Maja-Lisa Løchen ◽  
Tom Wilsgaard ◽  
Inger Njølstad ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Blood Pressure ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Pressure Management ◽  
Reference Models ◽  
Proportional Hazards Regression ◽  
Hazard Ratios ◽  
Increased Risk

The aim of this study was to explore sex-specific associations between systolic blood pressure (SBP), hypertension, and the risk of incident atrial fibrillation (AF) subtypes, including paroxysmal, persistent, and permanent AF, in a general population. A total of 13,137 women and 11,667 men who participated in the fourth survey of the Tromsø Study (1994–1995) were followed up for incident AF until the end of 2016. Cox proportional hazards regression analysis was conducted using fractional polynomials for SBP to provide sex- and AF-subtype-specific hazard ratios (HRs) for SBP. An SBP of 120 mmHg was used as the reference. Models were adjusted for other cardiovascular risk factors. Over a mean follow-up of 17.6 ± 6.6 years, incident AF occurred in 914 (7.0%) women (501 with paroxysmal/persistent AF and 413 with permanent AF) and 1104 (9.5%) men (606 with paroxysmal/persistent AF and 498 with permanent AF). In women, an SBP of 180 mmHg was associated with an HR of 2.10 (95% confidence interval [CI] 1.60–2.76) for paroxysmal/persistent AF and an HR of 1.80 (95% CI 1.33–2.44) for permanent AF. In men, an SBP of 180 mmHg was associated with an HR of 1.90 (95% CI 1.46–2.46) for paroxysmal/persistent AF, while there was no association with the risk of permanent AF. In conclusion, increasing SBP was associated with an increased risk of both paroxysmal/persistent AF and permanent AF in women, but only paroxysmal/persistent AF in men. Our findings highlight the importance of sex-specific risk stratification and optimizing blood pressure management for the prevention of AF subtypes in clinical practice.

scholarly journals Quantitative assessment of erector spinae muscles and prognosis in elderly patients with pneumonia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hiroki Yoshikawa ◽  
Kosaku Komiya ◽  
Takashi Yamamoto ◽  
Naoko Fujita ◽  
Hiroaki Oka ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Hospital Mortality ◽  
Regression Models ◽  
Proportional Hazards ◽  
Community Acquired Pneumonia ◽  
Cox Proportional Hazards ◽  
Erector Spinae ◽  
Cross Sectional ◽  
Proportional Hazards Regression ◽  
Survivor Group

AbstractErector spinae muscle (ESM) size has been reported as a predictor of prognosis in patients with some respiratory diseases. This study aimed to assess the association of ESM size on all-cause in-hospital mortality among elderly patients with pneumonia. We retrospectively included patients (age: ≥ 65 years) admitted to hospital from January 2015 to December 2017 for community-acquired pneumonia who underwent chest computed tomography (CT) on admission. The cross-sectional area of the ESM (ESMcsa) was measured on a single-slice CT image at the end of the 12th thoracic vertebra and adjusted by body surface area (BSA). Cox proportional hazards regression models were used to assess the influence of ESMcsa/BSA on in-hospital mortality. Among 736 patients who were admitted for pneumonia, 702 patients (95%) underwent chest CT. Of those, 689 patients (98%) for whom height and weight were measured to calculate BSA were included in this study. Patients in the non-survivor group were significantly older, had a greater frequency of respiratory failure, loss of consciousness, lower body mass index, hemoglobin, albumin, and ESMcsa/BSA. Multivariate analysis showed that a lower ESMcsa/BSA independently predicted in-hospital mortality after adjusting for these variables. In elderly patients with pneumonia, quantification of ESMcsa/BSA may be associated with in-hospital mortality.

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