Prognostic effect of inflammatory genes on stage I-III colorectal cancer – integrative analysis of TCGA data

2020 ◽  
Author(s):  
Eun Kyung Choe ◽  
Sangwoo Lee ◽  
So Yeon Kim ◽  
Manu Shivakumar ◽  
Kyu Joo Park ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Clinical Features ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Integrative Analysis ◽  
Stage I ◽  
The Cancer Genome Atlas ◽  
Integrative Model ◽  
Inflammatory Status

Abstract Background Inflammatory status indicators have been reported as a prognostic biomarker of colorectal cancer (CRC). However, since the inflammatory interactions with colon involve various modes of action, the biological mechanism to link inflammation and CRC prognosis is not fully elucidated. We comprehensively evaluated the predictive role of the expression and methylation level of inflammation-related genes for CRC prognosis and their pathophysiological associations. Method An integrative analysis was conducted on 247 patients of stage I-III CRC from The Cancer Genome Atlas. Lasso-penalized Cox proportional hazards regression (Lasso-Cox) and statistical Cox proportional hazard regression (CPH) were used for analysis. Result Models to predict overall survival were designed with respective combinations of clinical variables, including age, sex, stage, gene expression, and methylation. An integrative model combining expression, methylation, and clinical features had the highest performance (median C-index=0.756), compared to the model with clinical features alone (median C-index=0.726). By multivariate CPH with features from the best model, methylation levels of CEP250, RAB21 and TNPO3 were significantly associated with overall survival. They did not share any biological process in functional networks. The 5-year survival rate was 29.8% in a low methylation group of CEP250 and 79.1% in a high (P <0.001). Conclusion Our study result implicates the importance of integrating the expression and methylation information along with clinical information in prediction of survival. CEP250, RAB21 and TNPO3, in the prediction model might have a crucial role in CRC prognosis and further improve our understanding of potential mechanisms linking inflammatory reaction and CRC progression.

scholarly journals Prognostic Effect of Inflammatory Genes on Stage I–III Colorectal Cancer—Integrative Analysis of TCGA Data

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 751
Author(s):  
Eun Kyung Choe ◽  
Sangwoo Lee ◽  
So Yeon Kim ◽  
Manu Shivakumar ◽  
Kyu Joo Park ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Clinical Features ◽  
Cox Proportional Hazards ◽  
Integrative Analysis ◽  
Stage I ◽  
The Cancer Genome Atlas ◽  
Integrative Model ◽  
Inflammatory Status ◽  
Study Results

Background inflammatory status indicators have been reported as prognostic biomarkers of colorectal cancer (CRC). However, since inflammatory interactions with the colon involve various modes of action, the biological mechanism linking inflammation and CRC prognosis has not been fully elucidated. We comprehensively evaluated the predictive roles of the expression and methylation levels of inflammation-related genes for CRC prognosis and their pathophysiological associations. Method. An integrative analysis of 247 patients with stage I-III CRC from The Cancer Genome Atlas was conducted. Lasso-penalized Cox proportional hazards regression (Lasso-Cox) and statistical Cox proportional hazard regression (CPH) were used for the analysis. Results. Models to predict overall survival were designed with respective combinations of clinical variables, including age, sex, stage, gene expression, and methylation. An integrative model combining expression, methylation, and clinical features performed better (median C-index = 0.756) than the model with clinical features alone (median C-index = 0.726). Based on multivariate CPH with features from the best model, the methylation levels of CEP250, RAB21, and TNPO3 were significantly associated with overall survival. They did not share any biological process in functional networks. The 5-year survival rate was 29.8% in the low methylation group of CEP250 and 79.1% in the high methylation group (p < 0.001). Conclusion. Our study results implicate the importance of integrating expression and methylation information along with clinical information in the prediction of survival. CEP250, RAB21, and TNPO3 in the prediction model might have a crucial role in CRC prognosis and further improve our understanding of potential mechanisms linking inflammatory reactions and CRC progression.

scholarly journals Eps15 Homology Domain-Containing Protein 3 Hypermethylation as a Prognostic and Predictive Marker for Colorectal Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 453
Author(s):  
Yu-Han Wang ◽  
Shih-Ching Chang ◽  
Muhamad Ansar ◽  
Chin-Sheng Hung ◽  
Ruo-Kai Lin
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Mrna Expression ◽  
Proportional Hazards ◽  
Uterine Cancer ◽  
Colonic Polyps ◽  
Predictive Marker ◽  
Cox Proportional Hazards ◽  
The Cancer Genome Atlas ◽  
Eps15 Homology Domain

Colorectal cancer (CRC) arises from chromosomal instability, resulting from aberrant hypermethylation in tumor suppressor genes. This study identified hypermethylated genes in CRC and investigated how they affect clinical outcomes. Methylation levels of specific genes were analyzed from The Cancer Genome Atlas dataset and 20 breast cancer, 16 esophageal cancer, 33 lung cancer, 15 uterine cancer, 504 CRC, and 9 colon polyp tissues and 102 CRC plasma samples from a Taiwanese cohort. In the Asian cohort, Eps15 homology domain-containing protein 3 (EHD3) had twofold higher methylation in 44.4% of patients with colonic polyps, 37.3% of plasma from CRC patients, and 72.6% of CRC tissues, which was connected to vascular invasion and high microsatellite instability. Furthermore, EHD3 hypermethylation was detected in other gastrointestinal cancers. In the Asian CRC cohort, low EHD3 mRNA expression was found in 45.1% of patients and was connected to lymph node metastasis. Multivariate Cox proportional-hazards survival analysis revealed that hypermethylation in women and low mRNA expression were associated with overall survival. In the Western CRC cohort, EHD3 hypermethylation was also connected to overall survival and lower chemotherapy and antimetabolite response rates. In conclusion, EHD3 hypermethylation contributes to the development of CRC in both Asian and Western populations.

scholarly journals Survival rates and prognostic factors in right- and left-sided colon cancer stage I–IV: an unselected retrospective single-center trial

2021 ◽  
Author(s):  
Claudius E. Degro ◽  
Richard Strozynski ◽  
Florian N. Loch ◽  
Christian Schineis ◽  
Fiona Speichinger ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Blood Level ◽  
Proportional Hazards ◽  
Survival Rates ◽  
Cox Proportional Hazards ◽  
Stage I ◽  
Cancer Stage ◽  
Single Center ◽  
Significant Difference

Abstract Purpose Colorectal cancer revealed over the last decades a remarkable shift with an increasing proportion of a right- compared to a left-sided tumor location. In the current study, we aimed to disclose clinicopathological differences between right- and left-sided colon cancer (rCC and lCC) with respect to mortality and outcome predictors. Methods In total, 417 patients with colon cancer stage I–IV were analyzed in the present retrospective single-center study. Survival rates were assessed using the Kaplan–Meier method and uni/multivariate analyses were performed with a Cox proportional hazards regression model. Results Our study showed no significant difference of the overall survival between rCC and lCC stage I–IV (p = 0.354). Multivariate analysis revealed in the rCC cohort the worst outcome for ASA (American Society of Anesthesiologists) score IV patients (hazard ratio [HR]: 16.0; CI 95%: 2.1–123.5), CEA (carcinoembryonic antigen) blood level > 100 µg/l (HR: 3.3; CI 95%: 1.2–9.0), increased lymph node ratio of 0.6–1.0 (HR: 5.3; CI 95%: 1.7–16.1), and grade 4 tumors (G4) (HR: 120.6; CI 95%: 6.7–2179.6) whereas in the lCC population, ASA score IV (HR: 8.9; CI 95%: 0.9–91.9), CEA blood level 20.1–100 µg/l (HR: 5.4; CI 95%: 2.4–12.4), conversion to laparotomy (HR: 14.1; CI 95%: 4.0–49.0), and severe surgical complications (Clavien-Dindo III–IV) (HR: 2.9; CI 95%: 1.5–5.5) were identified as predictors of a diminished overall survival. Conclusion Laterality disclosed no significant effect on the overall prognosis of colon cancer patients. However, group differences and distinct survival predictors could be identified in rCC and lCC patients.

Effects of metformin and sulfonylureas on overall and colorectal cancer-specific mortality.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2599-2599
Author(s):  
Susan Spillane ◽  
Kathleen Bennett ◽  
Linda Sharp ◽  
Thomas Ian Barron
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Proportional Hazards ◽  
Early Stage ◽  
Population Based ◽  
Cox Proportional Hazards ◽  
Stage I ◽  
Early Stage Disease ◽  
All Cause Mortality ◽  
Specific Mortality

2599 Background: Preclinical studies have suggested a role for metformin in the treatment of colorectal cancer (CRC). Associations between metformin versus sulfonylurea exposure and mortality (all-cause and colorectal cancer specific) are assessed in this population-based study of patients with a diagnosis of stage I-IV CRC. Methods: National Cancer Registry Ireland records were linked to prescription claims data and used to identify a cohort of patients with incident TNM stage I-IV CRC diagnosed 2001-2006. From this cohort, 2 patient groups were identified and compared for outcomes - those who received a prescription for metformin +/- a sulfonylurea (MET) or a prescription for sulfonylurea alone (SUL) in the 90 days pre CRC diagnosis. Adjusted hazard ratios (HR) with 95% confidence intervals (CI) were estimated using Cox proportional hazards models adjusted for age, sex, stage, grade, site, comorbidities, year of diagnosis, and insulin, aspirin or statin exposure. Analyses were repeated stratifying by stage and site. Results: 5,617 patients with stage I-IV CRC were identified, of whom 369 received a prescription for metformin or a sulfonylurea in the 90 days pre diagnosis (median follow-up 1.6 years; MET: n=257; SUL: n=112). In adjusted analyses metformin exposure was associated with a 28% lower risk of all-cause mortality relative to sulfonylurea exposure (HR 0.72, 95% CI 0.53-0.98) and a non-significant 24% reduction in CRC-specific mortality (HR 0.76, 95% CI 0.52-1.13). In analyses stratified by site, in colon cancer, metformin exposure was associated with a significant one-third reduction in all-cause mortality (HR 0.66, 95% CI 0.46-0.95) and a non-significant reduction in site-specific mortality (HR 0.64, 95% CI 0.40-1.02). No mortality benefit was observed for rectal cancer. The association between metformin exposure and reduced mortality was strongest for stage I/II disease (all-cause mortality: HR 0.56, 95% CI 0.32-0.98; CRC-specific mortality: HR 0.48, 95% CI 0.21-1.11). Conclusions: Pre-diagnosis metformin exposure in CRC patients was associated with a significant reduction in mortality relative to sulfonylurea exposure. This benefit was greatest in patients with colon cancer and early stage disease.

scholarly journals Interstitial lung abnormalities in patients with stage I non-small cell lung cancer are associated with shorter overall survival: the Boston lung cancer study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tomoyuki Hida ◽  
Akinori Hata ◽  
Junwei Lu ◽  
Vladimir I. Valtchinov ◽  
Takuya Hino ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Small Cell ◽  
Stage I ◽  
Small Cell Lung ◽  
Lung Abnormalities

Abstract Background Interstitial lung abnormalities (ILA) can be detected on computed tomography (CT) in lung cancer patients and have an association with mortality in advanced non-small cell lung cancer (NSCLC) patients. The aim of this study is to demonstrate the significance of ILA for mortality in patients with stage I NSCLC using Boston Lung Cancer Study cohort. Methods Two hundred and thirty-one patients with stage I NSCLC from 2000 to 2011 were investigated in this retrospective study (median age, 69 years; 93 males, 138 females). ILA was scored on baseline CT scans prior to treatment using a 3-point scale (0 = no evidence of ILA, 1 = equivocal for ILA, 2 = ILA) by a sequential reading method. ILA score 2 was considered the presence of ILA. The difference of overall survival (OS) for patients with different ILA scores were tested via log-rank test and multivariate Cox proportional hazards models were used to estimate hazard ratios (HRs) including ILA score, age, sex, smoking status, and treatment as the confounding variables. Results ILA was present in 22 out of 231 patients (9.5%) with stage I NSCLC. The presence of ILA was associated with shorter OS (patients with ILA score 2, median 3.85 years [95% confidence interval (CI): 3.36 – not reached (NR)]; patients with ILA score 0 or 1, median 10.16 years [95%CI: 8.65 - NR]; P <  0.0001). In a Cox proportional hazards model, the presence of ILA remained significant for increased risk for death (HR = 2.88, P = 0.005) after adjusting for age, sex, smoking and treatment. Conclusions ILA was detected on CT in 9.5% of patients with stage I NSCLC. The presence of ILA was significantly associated with a shorter OS and could be an imaging marker of shorter survival in stage I NSCLC.

scholarly journals Expression and Prognostic Significance of NPC1L1 in Colorectal Cancer: A Retrospective Cohort Study

2021 ◽  
Author(s):  
Ryuk Jun Kwon ◽  
Soo Min Son ◽  
Eun Ju Park ◽  
Sang Yeoup Lee ◽  
Jungin Choi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Proportional Hazards ◽  
Prognostic Significance ◽  
Gene Expression Omnibus ◽  
Cox Proportional Hazards ◽  
The Cancer Genome Atlas ◽  
Rank Test ◽  
Chi Square ◽  
Independent Prognostic Marker ◽  
Niemann Pick

Abstract Background: Colorectal cancer (CRC) is a malignant tumor of the large intestine. Studies have shown that the development and prognosis of CRC are associated with altered lipid metabolism. Niemann-Pick C1-Like 1 (NPC1L1), the target of ezetimibe, plays an essential role in the absorption of intestinal cholesterol. However, the role of altered NPC1L1 expression in the development and prognosis of CRC has not yet been determined.Methods: Datasets of patients with CRC were obtained from The Cancer Genome Atlas (TCGA) database. To compare the expression of NPC1L1 in normal and CRC tissues, datasets obtained from the GDAC platform were used. To support these results, we also analyzed other datasets from the Gene Expression Omnibus (GEO) database. Student’s t-test and chi-square test were used for the analyses. The log-rank test and multivariate Cox proportional hazards regression analysis were performed to determine whether NPC1L1 is a significant factor affecting the prognosis of CRC.Results: The mRNA expression of NPC1L1 was found to be upregulated in CRC, and was significantly associated with the N- and pathological stages, but not with the histological type, age, and sex. Moreover, an increase in NPC1L1 expression in CRC was associated with poorer survival, based on the Kaplan–Meier and multivariate regression analyses.Conclusions: High expression of NPC1L1 is associated with CRC development, pathological stage, and prognosis. The present study suggests that NPC1L1 represents a potential independent prognostic marker for CRC.

Stereotactic radiotherapy for stage I renal cell carcinoma: Overall survival and treatment trends compared to thermal ablation and surgical resection.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16111-e16111
Author(s):  
Annemarie Uhlig ◽  
Johannes Uhlig ◽  
Lutz Trojan ◽  
Hyun S. Kim
Keyword(s):  
Overall Survival ◽  
Propensity Score ◽  
Stereotactic Radiotherapy ◽  
Renal Cell ◽  
Thermal Ablation ◽  
Proportional Hazards ◽  
Cell Cancer ◽  
Cox Proportional Hazards ◽  
Stage I ◽  
Invasive Treatment

e16111 Background: Stereotactic radiotherapy (SRT) is a non-invasive treatment modality that is currently evaluated for use in renal cell cancer (RCC). We aimed to evaluate current utilization of SRT for stage I RCC and compare associated overall survival with thermal ablation (TA) and partial nephrectomy (PN). Methods: The 2004-2015 United States National Cancer Database was searched for histopathologically approved stage I RCC treated with PN, cryoablation (CRA), radiofrequency- or microwave-ablation (RFA/MWA) or SRT. Patients were propensity score matched to account for potential confounders. Overall survival (OS) was evaluated with Kaplan-Meier plots, log-rank tests and Cox proportional hazards models. Results: A total of 91,965 patients were included (SRT n = 174; PN n = 82,913; CRA n = 5,446; RFA/MWA n = 3,432).Stage I SRT patients tended to be older females with fewer comorbidities and treated at non-academic centers in New England states. After propensity score matching, a cohort of n = 660 patients was obtained with well-balanced distribution of confounders between the different treatment strategies. In the matched cohort, OS following SRT was inferior to PN and thermal ablation (PN vs. SRT HR = 0.33, 95% CI: 0.22-0.50, p < 0.001; CRA vs. SRT HR = 0.44, 95% CI: 0.30 – 0.66, p < 0.001; RFA/MWA vs. SRT HR = 0.53, 95% CI: 0.36-0.77, p < 0.001). OS following CRA was comparable to PN (HR = 1.35, 95% CI: 0.84-2.18, p = 0.216), while OS following RFA/MWA was inferior to PN (HR = 1.61, 95% CI: 1.01-2.56, p = 0.046). OS rates are summarized in table 1. Conclusions: Only a minority of RCC patients receive SRT. In stage I RCC, current renal SRT protocols yield lower overall survival compared to thermal ablation and resection, while CRA and PN show comparable outcomes. Based on the current body of evidence, SRT for RCC should be reserved for clinical trials or exceptional clinical circumstances.[Table: see text]

scholarly journals Nomogram to Predict the Overall Survival of Colorectal Cancer Patients: A Multicenter National Study

2021 ◽  
Vol 18 (15) ◽  
pp. 7734
Author(s):  
Nasrin Borumandnia ◽  
Hassan Doosti ◽  
Amirhossein Jalali ◽  
Soheila Khodakarim ◽  
Jamshid Yazdani Charati ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Family History ◽  
Clinical Decision Making ◽  
Proportional Hazards ◽  
Clinical Decision ◽  
Tumor Stage ◽  
Cox Proportional Hazards ◽  
National Study ◽  
Historical Cohort

Background: Colorectal cancer (CRC) is the third foremost cause of cancer-related death and the fourth most commonly diagnosed cancer globally. The study aimed to evaluate the survival predictors using the Cox Proportional Hazards (CPH) and established a novel nomogram to predict the Overall Survival (OS) of the CRC patients. Materials and methods: A historical cohort study, included 1868 patients with CRC, was performed using medical records gathered from Iran’s three tertiary colorectal referral centers from 2006 to 2019. Two datasets were considered as train set and one set as the test set. First, the most significant prognostic risk factors on survival were selected using univariable CPH. Then, independent prognostic factors were identified to construct a nomogram using the multivariable CPH regression model. The nomogram performance was assessed by the concordance index (C-index) and the time-dependent area under the ROC curve. Results: The age of patients, body mass index (BMI), family history, tumor grading, tumor stage, primary site, diabetes history, T stage, N stage, and type of treatment were considered as significant predictors of CRC patients in univariable CPH model (p < 0.2). The multivariable CPH model revealed that BMI, family history, grade and tumor stage were significant (p < 0.05). The C-index in the train data was 0.692 (95% CI, 0.650–0.734), as well as 0.627 (0.670, 0.686) in the test data. Conclusion: We improved a novel nomogram diagram according to factors for predicting OS in CRC patients, which could assist clinical decision-making and prognosis predictions in patients with CRC.

scholarly journals SELE gene as a characteristic prognostic biomarker of colorectal cancer

2021 ◽  
Vol 49 (4) ◽  
pp. 030006052110043
Author(s):  
Na Li ◽  
Honghe Xiao ◽  
Jiangli Shen ◽  
Ximin Qiao ◽  
Fenjuan Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Proportional Hazards ◽  
Cox Regression ◽  
Expression Profiles ◽  
Immunohistochemical Analysis ◽  
Cox Proportional Hazards ◽  
The Cancer Genome Atlas ◽  
Clinical Value ◽  
Cox Regression Analysis

Objective To investigate the expression and clinical value of the E-selectin gene ( SELE) in colorectal cancer (CRC). Methods Using gene expression profiles and clinicopathological data for patients with CRC from The Cancer Genome Atlas, and tumor and adjacent normal tissues from 31 patients with CRC from Xianyang Central Hospital, we studied the correlation between SELE gene expression and clinical parameters using Kaplan–Meier and Cox proportional hazards regression analyses. Results Higher expression of SELE was significantly associated with a poorer prognosis and shorter survival in patients with CRC. The median expression level of SELE was significantly higher in CRC tissues compared with healthy adjacent tissue. Cox regression analysis showed that the prognosis of CRC was significantly correlated with the expression of SELE. Immunohistochemical analysis also showed that positive expression of E-selectin increased significantly in line with increasing TNM stage. Conclusion: This study confirmed that SELE gene expression is an independent prognostic factor in patients with CRC.

The outcome of patients with stage I endometrial cancer involving the lower uterine segment

2008 ◽  
Vol 18 (5) ◽  
pp. 1079-1083 ◽  
Author(s):  
O. Lavie ◽  
L. Uriev ◽  
M. Gdalevich ◽  
F. Barak ◽  
G. Peer ◽  
...  
Keyword(s):  
Overall Survival ◽  
Endometrial Carcinoma ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Myometrial Invasion ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Stage I ◽  
Rank Test ◽  
Log Rank Test

The objective of this study was to evaluate whether lower uterine segment involvement (LUSI) correlates with recurrence and survival in women with stage I endometrial adenocarcinoma and whether it is associated with poor prognostic histopathologic features. Three hundred seventy-five consecutive patients with endometrial carcinoma stage I compromised the study population. The patients were divided into two groups according to the presence of LUSI with endometrial carcinoma. The two groups were compared with regard to prognostic factors and outcome measures by using the Pearson χ2 test, log-rank test, and Cox proportional hazards model. LUSI was present in 89 (24%) patients with stage I endometrial carcinoma. LUSI was significantly associated with grade 3 tumor (P= 0.022), deep myometrial invasion (P< 0.0001), and the presence of capillary space-like involvement (CSLI) (P= 0.003). Kaplan–Meier survival curves demonstrated that patients with LUSI had a lower recurrence-free survival (log-rank test; P= 0.009) and a worse overall survival (log-rank test; P= 0.0008). In the Cox proportional hazards model, only a trend toward higher recurrence rate (HR = 2.4, 95% CI 0.7, 8.2; P= 0.16) and a trend toward poorer overall survival (HR = 1.54, 95% CI 0.82, 2.91; P= 0.18) were noted when LUSI was present. In patients with stage I endometrial cancer, the presence of LUSI is associated with grade 3 tumor, deep myometrial invasion, and the presence of CSLI. A larger group of patients is necessary to conclude whether higher recurrence rate and poorer overall survival are associated with the presence of LUSI.

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