Construction of methylation-associated nomogram for predicting the recurrence-free survival risk of stage I–III lung adenocarcinoma

2021 ◽  
Author(s):  
Youcai Liu ◽  
Bin Wang ◽  
Shiqiang Shi ◽  
Zhaoxi Li ◽  
Yajuan Wang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Lung Adenocarcinoma ◽  
Operating Characteristic ◽  
Cox Regression ◽  
Stage I ◽  
Recurrence Free Survival ◽  
Characteristic Analysis ◽  
Free Survival ◽  
Selection Operator ◽  
Survival Risk

Aim: The aim of our study was to investigate a methylation-associated predictor for prognosis in patients with stage I–III lung adenocarcinoma (LUAD). Methods: A DNA methylation-based signature was developed via univariate, least absolute shrinkage and selection operator and multivariate Cox regression models. Results: We identified a 14-site methylation signature that was correlated with recurrence-free survival of stage I–III lung adenocarcinoma patients. By receiver operating characteristic analysis, we showed the high ability of the 14-site methylation signature for predicting recurrence-free survival. In addition, the nomogram result showed a satisfactory predictive value. Conclusion: We successfully identified a DNA methylation-associated nomogram which can predict recurrence-free survival in patients with stage I–III lung adenocarcinoma.

Utility of a metabolic-associated nomogram to predict the recurrence-free survival of stage I cervical cancer

2021 ◽  
Vol 17 (11) ◽  
pp. 1325-1337
Author(s):  
Yan Zhang ◽  
Huan Lu ◽  
Jinjin Zhang ◽  
Shixuan Wang
Keyword(s):  
Cervical Cancer ◽  
Risk Score ◽  
Cox Regression ◽  
Area Under The Curve ◽  
Gene Expression Omnibus ◽  
Stage I ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Cox Analysis

Aims: To identify metabolism-associated genes (MAGs) that serve as biomarkers to predict prognosis associated with recurrence-free survival (RFS) for stage I cervical cancer (CC). Patients & methods: By analyzing the Gene Expression Omnibus (GEO) database for 258 cases of stage I CC via univariate Cox analysis, LASSO and multivariate Cox regression analysis, we unveiled 11 MAGs as a signature that was also validated using Kaplan–Meier and receiver operating characteristic analyses. In addition, a metabolism-related nomogram was developed. Results: High accuracy of this signature for prediction was observed (area under the curve at 1, 3 and 5 years was 0.964, 0.929 and 0.852 for the internal dataset and 0.759, 0.719 and 0.757 for the external dataset). The high-risk score group displayed markedly worse RFS than did the low-risk score group. The indicators performed well in our nomogram. Conclusions: We identified a novel signature as a biomarker for predicting prognosis and a nomogram to facilitate the individual management of stage I CC patients.

scholarly journals A Molecule Based Nomogram Optimized the Prediction of Relapse in Stage I NSCLC

2021 ◽  
Author(s):  
Rongrong Bian ◽  
Guorong Zhu ◽  
Feng Zhao ◽  
Rui Chen ◽  
Wengji Xia ◽  
...  
Keyword(s):  
Cox Regression ◽  
Early Stage ◽  
External Validation ◽  
Stage I ◽  
Recursive Feature Elimination ◽  
Support Vector ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Training Cohort ◽  
Discovery Phase

Abstract Background: Early-stage non-small cell lung cancer (NSCLC) is being diagnosed increasingly, and in 30% of diagnosed patients, recurrence will develop within 5 years. Thus, it is urgent to identify recurrence-related markers in order to optimize the management of patient-tailored therapeutics. The aim of the study was to develop a feasible tool to optimize the recurrence prediction of stage I NSCLC. Methods: The eligible datasets were downloaded from TCGA and GEO. In discovery phase, two algorithms, Least Absolute Shrinkage and Selector Operation and Support Vector Machine-Recursive Feature Elimination, were used to identify candidate genes. Recurrence associated signature was developed by penalized cox regression. The nomogram was constructed and further tested via two independent cohorts. Results: In this retrospective study, 14 eligible datasets and 7 published signatures were included. In discovery phase, 42 significant genes were highlighted as candidate predictors by two algorithms. A 13-gene based signature was generated by penalized cox regression categorized training cohort into high-risk and low-risk subgroups (HR = 8.873, 95% CI:4.228–18.480 P < 0.001). Furthermore, a nomogram integrating the recurrence related signature, age, and histology was developed to predict the recurrence-free survival in the training cohort, which performed well in the two external validation cohorts (concordance index: 0.737, 95%CI:0.732–0.742, P < 0.001; 0.666, 95%CI: 0.650–0.682, P < 0.001; 0.651, 95%CI:0.637–0.665, P < 0.001 respectively). Conclusions: The proposed nomogram is a promising tool for estimating recurrence free survival in stage I NSCLC, which might have tremendous value in guiding adjuvant therapy. Prospective studies are needed to test the clinical utility of the nomogram in individualized management of stage I NSCLC.

scholarly journals Individualized Prediction of Stage I Colorectal Cancer Recurrence Using a Nomogram

2021 ◽  
Author(s):  
Aobo Zhuang ◽  
Dexiang Zhu ◽  
Qi Lin ◽  
Pingping Xu ◽  
Guodong He ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Recurrence Rate ◽  
Cox Regression ◽  
Radical Surgery ◽  
Cancer Recurrence ◽  
Stage I ◽  
Recurrence Free Survival ◽  
Curative Surgery ◽  
Free Survival ◽  
Preoperative Serum

Abstract Background Though the prognosis of stage l colorectal cancer (CRC) is suitable, some patients still recurrence and have a poor prognosis. Few prognostic risk models have been proposed. Therefore, we aimed to identify factors affecting the recurrence in patients with stage I CRC and develop a predictive nomogram. Methods The nomogram was based on a retrospective study on patients who underwent radical surgery for stage I CRC at Zhongshan Hospital (Shanghai, China) between August 2008 and December 2016. Predictive factors for recurrence were determined and a nomogram predicting recurrence-free survival was constructed based on Cox regression. This model was internally validated, and performance was evaluated through calibration plots. Results A total of 1,359 patients who underwent curative surgery for stage I CRC were enrolled. With the 62.0 months median follow-up time,71 (5.2%) experienced recurrence. The median time to recurrence was 24 months, 70% was diagnosed within three years after curative resection and 80% within 5 years. The 5-year cumulative recurrence rate was 5.0%, and the 10-year recurrence rate was 6.6%. In multivariate Cox analysis, age, preoperative serum CEA concentration, preoperative serum CA19-9 concentration, preoperative neutrophil-to-lymphocyte ratio, primary tumor location and lymphovascular invasion were the independent predictors of recurrence. A nomogram based on eight factors for recurrence-free survival was developed and internally validated. The concordance index of the nomogram was 0.716. Conclusions For stage I CRC, more than one in every twenty people may experience recurrence within 10 years after radical surgery. The nomogram we developed and internally validated might be helpfulhelpful in postoperative stage I CRC surveillance.

scholarly journals Novel Gene Signatures Predictive of Patient Recurrence-Free Survival and Castration Resistance in Prostate Cancer

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 917
Author(s):  
Jun A ◽  
Baotong Zhang ◽  
Zhiqian Zhang ◽  
Hailiang Hu ◽  
Jin-Tang Dong
Keyword(s):  
Prostate Cancer ◽  
Cox Regression ◽  
Characteristic Curve ◽  
Treatment Decision ◽  
Rank Aggregation ◽  
Lymph Node Status ◽  
Calibration Plot ◽  
Recurrence Free Survival ◽  
Castration Resistance ◽  
Free Survival

Molecular signatures predictive of recurrence-free survival (RFS) and castration resistance are critical for treatment decision-making in prostate cancer (PCa), but the robustness of current signatures is limited. Here, we applied the Robust Rank Aggregation (RRA) method to PCa transcriptome profiles and identified 287 genes differentially expressed between localized castration-resistant PCa (CRPC) and hormone-sensitive PCa (HSPC). Least absolute shrinkage and selection operator (LASSO) and stepwise Cox regression analyses of the 287 genes developed a 6-gene signature predictive of RFS in PCa. This signature included NPEPL1, VWF, LMO7, ALDH2, NUAK1, and TPT1, and was named CRPC-derived prognosis signature (CRPCPS). Interestingly, three of these 6 genes constituted another signature capable of distinguishing CRPC from HSPC. The CRPCPS predicted RFS in 5/9 cohorts in the multivariate analysis and remained valid in patients stratified by tumor stage, Gleason score, and lymph node status. The signature also predicted overall survival and metastasis-free survival. The signature’s robustness was demonstrated by the C-index (0.55–0.74) and the calibration plot in all nine cohorts and the 3-, 5-, and 8-year area under the receiver operating characteristic curve (0.67–0.77) in three cohorts. The nomogram analyses demonstrated CRPCPS’ clinical applicability. The CRPCPS thus appears useful for RFS prediction in PCa.

scholarly journals Postoperative non-steroidal anti-inflammatory drug use and oncological outcomes of rectal cancer

BJS Open ◽  
2021 ◽  
Vol 5 (1) ◽  
Author(s):  
O Grahn ◽  
M Lundin ◽  
M-L Lydrup ◽  
E Angenete ◽  
M Rutegård
Keyword(s):  
Rectal Cancer ◽  
Propensity Score ◽  
Propensity Score Matching ◽  
Instrumental Variables ◽  
Cox Regression ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Oncological Outcomes ◽  
Anti Inflammatory ◽  
Instrumental Variables Approach

Abstract Background Non-steroidal anti-inflammatory drugs (NSAIDs) are known to suppress the inflammatory response after surgery and are often used for pain control. This study aimed to investigate NSAID use after radical surgical resection for rectal cancer and long-term oncological outcomes. Methods A cohort of patients who underwent anterior resection for rectal cancer between 2007 and 2013 in 15 hospitals in Sweden was investigated retrospectively. Data were obtained from the Swedish Colorectal Cancer Registry and medical records; follow-up was undertaken until July 2019. Patients who received NSAID treatment for at least 2 days after surgery were compared with controls who did not, and the primary outcome was recurrence-free survival. Cox regression modelling with confounder adjustment, propensity score matching, and an instrumental variables approach were used; missing data were handled by multiple imputation. Results The cohort included 1341 patients, 362 (27.0 per cent) of whom received NSAIDs after operation. In analyses using conventional regression and propensity score matching, there was no significant association between postoperative NSAID use and recurrence-free survival (adjusted hazard ratio (HR) 1.02, 0.79 to 1.33). The instrumental variables approach, including individual hospital as the instrumental variable and clinicopathological variables as co-variables, suggested a potential improvement in the NSAID group (HR 0.61, 0.38 to 0.99). Conclusion Conventional modelling did not demonstrate an association between postoperative NSAID use and recurrence-free survival in patients with rectal cancer, although an instrumental variables approach suggested a potential benefit.

scholarly journals The impact of method of distal ureter management during radical nephroureterectomy on tumour recurrence

2014 ◽  
Vol 8 (11-12) ◽  
pp. 845 ◽  
Author(s):  
Anil Kapoor ◽  
Shawn Dason ◽  
Christopher B. Allard ◽  
Bobby Shayegan ◽  
Louis Lacombe ◽  
...  
Keyword(s):  
Cox Regression ◽  
Tumour Recurrence ◽  
Management Approach ◽  
Management Technique ◽  
Recurrence Free Survival ◽  
Radical Nephroureterectomy ◽  
Distal Ureter ◽  
Free Survival ◽  
Cox Regression Analysis

Introduction: Radical nephroureterectomy for upper tract urothelial carcinoma (UTUC) must include some form of distal ureter management to avoid high rates of tumour recurrence. It is uncertain which distal ureter management technique has the best oncologic outcomes. To determine which distal ureter management technique resulted in the lowest tumour recurrence rate, we analyzed a multiinstitutional Canadian radical nephroureterectomy database.Methods: We retrospectively analyzed patients who underwent radical nephroureterectomy with distal ureter management for UTUC between January 1990 and June 2010 at 10 Canadian tertiary hospitals. Distal ureter management approaches were divided into 3 categories: (1) extravesical tenting for ureteric excision without cystotomy (EXTRAVESICAL); (2) open cystotomy with intravesical bladder cuff excision (INTRAVESICAL); and (3) extravesical excision with endoscopic management of ureteric orifice (ENDOSCOPIC). Data available for each patient included demographic details, distal ureter management approach, pathology and operative details, as well as the presence and location of local or distant recurrence. Clinical outcomes included overall recurrence-free survival and intravesical recurrence-free survival. Survival analysis was performed with the Kaplan-Meier method. Multivariable Cox regression analysis was also performed.Results: A total of 820 patients underwent radical nephroureterectomy with a specified distal ureter management approach at 10 Canadian academic institutions. The mean patient age was 69.6 years and the median follow-up was 24.6 months. Of the 820 patients, 406 (49.5%) underwent INTRAVESICAL, 316 (38.5%) underwent EXTRAVESICAL, and 98 (11.9%) underwent ENDOSOPIC distal ureter management. Groups differed significantly in their proportion of females, proportion of laparoscopic cases, presence of carcinoma in situ and pathological tumour stage (p < 0.05). Recurrence-free survival at 5 years was 46.3%, 35.6%, and 30.1% for INTRAVESICAL, EXTRAVESICAL and ENDOSCOPIC, respectively (p < 0.05). Multivariable Cox regression analysis confirmed that INTRAVESICAL resulted in a lower hazard of recurrence compared to EXTRAVESICAL and ENDOSCOPIC. When looking only at intravesical recurrence-free survival (iRFS), a similar trend held up with INTRAVESICAL having the highest iRFS, followed by ENDOSCOPIC and then EXTRAVESICAL management (p < 0.05). At last follow-up, 406 (49.5%) patients were alive and free of disease.Conclusion: Open intravesical excision of the distal ureter (INTRAVESICAL) during radical nephroureterectomy was associated with improved overall and intravesical recurrence-free survival compared with extravesical and endoscopic approaches. These findings suggest that INTRAVESICAL should be considered the gold standard oncologic approach to distal ureter management during radical nephroureterectomy. Limitations of this study include its retrospective design, heterogeneous cohort, and limited follow-up.

scholarly journals Increased GOLM1 Expression Independently Predicts Unfavorable Overall Survival and Recurrence-Free Survival in Lung Adenocarcinoma

2018 ◽  
Vol 25 (1) ◽  
pp. 107327481877800 ◽  
Author(s):  
Xi Liu ◽  
Lei Chen ◽  
Tao Zhang
Keyword(s):  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Survival Data ◽  
Methylation Status ◽  
Lung Squamous Cell Carcinoma ◽  
Prognostic Indicator ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Recurrence Free Survival ◽  
Free Survival

Golgi membrane protein 1 (GOLM1) is a transmembrane glycoprotein of the Golgi cisternae, which is implicated in carcinogenesis of multiple types of cancer. In this study, using data from the Gene Expression Omnibus and The Cancer Genome Atlas, we compared the expression of GOLM1 in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) and studied its prognostic value in terms of overall survival (OS) and recurrence-free survival (RFS) in these 2 subtypes of non-small cell lung cancer (NSCLC). Results showed that GOLM1 was significantly upregulated in both LUAD and LUSC tissues compared to the normal controls. However, GOLM1 expression was higher in LUAD tissues than in LUSC tissues. More importantly, using over 10 years’ survival data from 502 patients with LUAD and 494 patients with LUSC, we found that high GOLM1 expression was associated with unfavorable OS and RFS in patients with LUAD, but not in patients with LUSC. The following univariate and multivariate analyses confirmed that increased GOLM1 expression was an independent prognostic indicator of poor OS (hazard ratio [HR]: 1.30, 95% confidence interval [CI]: 1.11-1.54, P = .002) and RFS (HR: 1.37, 95% CI: 1.14-1.64, P = .001) in patients with LUAD. Of 511 cases with LUAD, 248 (48.5%) had heterozygous loss (−1), while 28 (5.5%) of 511 cases with LUAD had low-level copy gain (+1). In addition, we also found that the methylation status of 1 CpG site (chr9: 88,694,942-88,694,944) showed a weak negative correlation with GOLM1 expression (Pearson r = −0.25). Based on these findings, we infer that GOLM1 might serve as a valuable prognostic biomarker in LUAD, but not in LUSC. In addition, DNA copy number alterations and methylation might be 2 important mechanisms of dysregulated GOLM1 in LUAD.

Biomarker panels may be superior over single molecules in prediction of renal flares in systemic lupus erythematosus: an exploratory study

Rheumatology ◽  
2020 ◽  
Vol 59 (11) ◽  
pp. 3193-3200
Author(s):  
Serena Fasano ◽  
Luciana Pierro ◽  
Alessia Borgia ◽  
Melania Alessia Coscia ◽  
Ranieri Formica ◽  
...  
Keyword(s):  
Receiver Operating Characteristic ◽  
Adhesion Molecule ◽  
Operating Characteristic ◽  
Cox Regression ◽  
Receiver Operating Characteristic Analysis ◽  
Characteristic Analysis ◽  
Factors Associated ◽  
Biomarker Panel ◽  
Renal Flare ◽  
Receiver Operating

Abstract Objective Recent evidence suggests that some urinary biomarkers, namely Vascular Cell Adhesion Molecule-1 (VCAM-1), Intercellular Adhesion Molecule-1 (ICAM-1), Monocyte Chemoattractant Protein 1 (MCP-1), Neutrophil Gelatinase Associated Lipocalcin and Lipocalin-type Prostaglandin D-Synthetase (L-PGDS), might discriminate SLE patients with ongoing renal activity from those with stable disease. The objective of this study was to assess the role of these markers in predicting renal flares in comparison with conventional biomarkers and to derive a biomarker panel which may improve diagnostic accuracy. Methods Eligible participants were SLE patients prospectively followed at our clinic. Urinary biomarker levels were measured in urinary sample by ELISA assay and were compared by the unpaired Student’s t test or the Mann–Whitney U test as appropriate. Receiver operating characteristic analysis was used to calculate the area under the curve. Cox regression was used to identify independent factors associated with disease flares. Results Urine was collected from 61 patients. During 8 months’ follow-up, eight patients experienced a renal flare. Urinary L-PGDS, ICAM-1 and VCAM-1 levels were significantly increased in the patients who subsequently experienced a renal flare with respect to the remaining 53. At Cox regression analysis, L-PGDS, ICAM-1, VCAM-1, hypocomplementemia and anti-dsDNA antibodies were factors associated with renal flares. Based on receiver operating characteristic analysis, a combination of novel and conventional biomarkers demonstrated an excellent ability for accurately identifying a flare. Conclusion This study might suggest the usefulness of a novel biomarker panel in predicting a renal flare in SLE.

Blood and tumor inflammation markers in non-small cell lung cancer (NSCLC): Blood leukocytosis as an independent risk factor in early stage.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21110-e21110
Author(s):  
Andreas Carus ◽  
Morten Ladekarl ◽  
Henrik Hager ◽  
Hans Pilegaard ◽  
Patricia Switten Nielsen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factor ◽  
Stage I ◽  
Stage Ii ◽  
Recurrence Free Survival ◽  
Elevated Blood ◽  
Blood Leukocytes ◽  
Cancer Specific Survival ◽  
Free Survival ◽  
Cancer Inflammation

e21110 Background: Cancer inflammation is associated with impaired survival in a range of cancers. We reviewed blood and intratumoral inflammatory markers in NSCLC. Methods: At the Departmentof Thoracic Surgery, Skejby Hospital, Aarhus, Denmark, consecutive patients with resected NSCLC from 2000 to 2008 were reviewed, and 906 patients with complete clinical data were identified. A subset of 341 consecutive patients, resected between 2003 and 2006, also had intratumoral CD66b+ neutrophils and CD163+ macrophages measured by immunohistochemistry and evaluated by stereological assessment. Results: A total of 526, 197, and 183 patients had stage I, II, and III, respectively. Multivariate analysis stratified for tumor stage revealed elevated blood leukocytes above upper limit of normal as a significant prognostic factor for recurrence-free survival (RFS)(hazard ratio [HR] 1.9; 95% CI 1.4-2.6; p<0.0001), cancer specific survival (CSS)(HR 1.9; 95% CI 1.4-2.7; p<0.0001), and overall survival (OS)(HR 1.5; 95% CI 1.1-1.9; p<0.006) in stage I NSCLC, but not in stage II and III. No prognostic impact of intratumoral neutrophils or macrophages was seen on CSS, RFS, or OS, neither in the entire cohort, nor limited to stage I patients with elevated blood leukocytes or with normal counts. Controlling intratumoral neutrophils and macrophages for localization restricted to tumor tissue, stromal tissue, or blood vessels, respectively, were also with no statistically significant difference. Conclusions: Blood leukocytosis is an independent prognostic factor for short recurrence free survival, cancer specific survival, and overall survival in stage I NSCLC, but not in stage II and III. However, intratumoral neutrophils or macrophages did not impact prognosis. Further studies are needed to elucidate the role of cancer inflammation in NSCLC.

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