scholarly journals The Prognostic Significance of Tumor Deposit Count for Colorectal Cancer Patients after Radical Surgery

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Kuo Zheng ◽  
Nanxin Zheng ◽  
Cheng Xin ◽  
Leqi Zhou ◽  
Ge Sun ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Value ◽  
Validation Cohort ◽  
Cutoff Point ◽  
Disease Specific Survival ◽  
Optimal Cutoff ◽  
Training Cohort ◽  
Tumor Deposit ◽  
Optimal Cutoff Point ◽  
Disease Specific

Background. The prognostic value of tumor deposit (TD) count in colorectal cancer (CRC) patients has been rarely evaluated. This study is aimed at exploring the prognostic value of TD count and finding out the optimal cutoff point of TD count to differentiate the prognoses of TD-positive CRC patients. Method. Patients diagnosed with CRC from Surveillance, Epidemiology, and End Results (SEER) database from January 1, 2010, to December 31, 2012, were analyzed. X-tile program was used to identify the optimal cutoff point of TD count in training cohort, and a validation cohort was used to test this cutoff point after propensity score matching (PSM). Univariate and multivariate Cox proportional hazard models were used to assess the risk factors of survival. Results. X-tile plots identified 3 (P<0.001) as the optimal cutoff point of TD count to divide the patients of training cohort into high and low risk subsets in terms of disease-specific survival (DSS). This cutoff point was validated in validation cohort before and after PSM (P<0.001, P=0.002). More TD count, which was defined as more than 3, was validated as an independent risk prognostic factor in univariate and multivariate analysis (P<0.001). Conclusion. More TD count (TD count≥4) was significantly associated with poor disease-specific survival in CRC patients.

Identifying an immune-related gene-pair for prognosis prediction of metastatic colorectal cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15565-e15565
Author(s):  
Qiqi Zhu ◽  
Du Cai ◽  
Wei Wang ◽  
Min-Er Zhong ◽  
Dejun Fan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Prognostic Value ◽  
Validation Cohort ◽  
Risk Group ◽  
High Risk Group ◽  
Related Gene ◽  
Training Cohort ◽  
Gene Pairs ◽  
Immune Related Gene

e15565 Background: Few robust predictive biomarkers have been applied in clinical practice due to the heterogeneity of metastatic colorectal cancer (mCRC) . Using the gene pair method, the absolute expression value of genes can be converted into the relative order of genes, which can minimize the influence of the sequencing platform difference and batch effects, and improve the robustness of the model. The main objective of this study was to establish an immune-related gene pairs signature (IRGPs) and evaluate the impact of the IRGPs in predicting the prognosis in mCRC. Methods: A total of 205 mCRC patients containing overall survival (OS) information from the training cohort ( n = 119) and validation cohort ( n = 86) were enrolled in this study. LASSO algorithm was used to select prognosis related gene pairs. Univariate and multivariate analyses were used to validate the prognostic value of the IRGPs. Gene sets enrichment analysis (GSEA) and immune infiltration analysis were used to explore the underlying biological mechanism. Results: An IRGPs signature containing 22 gene pairs was constructed, which could significantly separate patients of the training cohort ( n = 119) and validation cohort ( n = 86) into the low-risk and high-risk group with different outcomes. Multivariate analysis with clinical factors confirmed the independent prognostic value of IRGPs that higher IRGPs was associated with worse prognosis (training cohort: hazard ratio (HR) = 10.54[4.99-22.32], P < 0.001; validation cohort: HR = 3.53[1.24-10.08], P = 0.012). GSEA showed that several metastasis and immune-related pathway including angiogenesis, TGF-β-signaling, epithelial-mesenchymal transition and inflammatory response were enriched in the high-risk group. Through further analysis of the immune factors, we found that the proportions of CD4+ memory T cell, regulatory T cell, and Myeloid dendritic cell were significantly higher in the low-risk group, while the infiltrations of the Macrophage (M0) and Neutrophil were significantly higher in the high-risk group. Conclusions: The IRGPs signature could predict the prognosis of mCRC patients. Further prospective validations are needed to confirm the clinical utility of IRGPs in the treatment decision.

scholarly journals Deep learning quantified mucus-tumor ratio predicting survival of patients with colorectal cancer using whole-slide images

2021 ◽  
Author(s):  
Ke Zhao ◽  
Lin Wu ◽  
Yanqi Huang ◽  
Su Yao ◽  
Zeyan Xu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Deep Learning ◽  
Prognostic Value ◽  
Validation Cohort ◽  
Survival Rates ◽  
Training Cohort ◽  
Mucinous Component ◽  
Hematoxylin And Eosin ◽  
High Consistency ◽  
Whole Slide Images

Abstract Background In colorectal cancer (CRC), mucinous adenocarcinoma differs from other adenocarcinomas in gene-phenotype, morphology, and prognosis. However, mucinous components are present in a large amount of adenocarcinoma, and the prognostic value of mucus proportion has not been investigated. Artificial intelligence provides a way to quantify mucus proportion on whole-slide images (WSIs) accurately. We aimed to quantify mucus proportion by deep learning and further investigate its prognostic value in two CRC patients cohorts. Methods Deep learning was used to segment WSIs stained with hematoxylin and eosin. Mucus-tumor ratio (MTR) was defined as the proportion of mucinous component in the tumor area. A training cohort (N = 419) and a validation cohort (N = 315) were used to evaluate the prognostic value of MTR. Survival analysis was performed by the Cox proportional hazard model. Result Patients were stratified to mucus-low and mucus-high groups by 24.1% as the threshold. In the training cohort, patients with mucus-high had unfavorable outcomes (hazard ratio for high vs. low 1.88, 95% confidence interval 1.18-2.99, P = 0.008), with 5-year overall survival rates of 54.8% and 73.7% in mucus-high and mucus-low groups, respectively. The results were confirmed in the validation cohort (2.09, 1.21-3.60, 0.008; 79.8% vs. 62.8%). The prognostic value of MTR was maintained in multivariate analysis for both cohorts. Conclusion The deep learning quantified MTR was an independent prognostic factor in CRC. With the advantages of advanced efficiency and high consistency, our method is suitable for clinical application and promotes precision medicine development.

scholarly journals Long non-coding RNA profile study identifies a metabolism-related signature for colorectal cancer

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Yongqu Lu ◽  
Wendong Wang ◽  
Zhenzhen Liu ◽  
Junren Ma ◽  
Xin Zhou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Score ◽  
Roc Curve ◽  
Prognostic Value ◽  
Clinical Decision Making ◽  
Validation Cohort ◽  
Gene Set Enrichment Analysis ◽  
Training Cohort ◽  
Non Coding Rna ◽  
Long Non Coding Rna

Abstract Background Heterogeneity in colorectal cancer (CRC) patients provides novel strategies in clinical decision-making. Identifying distinctive subgroups in patients can improve the screening of CRC and reduce the cost of tests. Metabolism-related long non-coding RNA (lncRNA) can help detection of tumorigenesis and development for CRC patients. Methods RNA sequencing and clinical data of CRC patients which extracted and integrated from public databases including The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were set as training cohort and validation cohort. Metabolism-related genes were acquired from Kyoto Encyclopedia of Genes and Genomes (KEGG) and the metabolism-related lncRNAs were filtered using correlation analysis. The risk score was calculated based on lncRNAs with prognostic value and verified through survival curve, receiver operating characteristic (ROC) curve and risk curve. Prognostic factors of CRC patients were also analyzed. Nomogram was constructed based on the results of cox regression analyses. The different immune status was observed in the single sample Gene Set Enrichment Analysis (ssGSEA). Results The training cohort and the validation cohort enrolled 432 and 547 CRC patients respectively. A total of 23 metabolism-related lncRNAs with prognostic value were screened out and 10 of which were significantly differentially expressed between tumour and normal tissues. Finally, 8 lncRNAs were used to establish a risk score (DICER1-AS1, PCAT6, GAS5, PRR7-AS1, MCM3AP-AS1, GAS6-AS1, LINC01082 and ADIRF-AS1). Patients were divided into high-risk and low-risk groups according to the median of risk scores in training cohort and the survival curves indicated that the survival prognosis was significantly different. The area under curve (AUC) of the ROC curve in two cohorts were both greater than 0.6. The age, tumour stage and risk score were selected as independent factors and used to construct a nomogram to predict CRC patients' survival rate with the c-index of 0.806. The ssGSEA indicated that the risk score was associated with immune cells and functions. Conclusions Our systematic study established a metabolism-related lncRNA signature to predict outcomes of CRC patients which may contribute to individual prevention and treatment.

scholarly journals The Prognostic Value of Preoperative Serum Lactate Dehydrogenase (LDH) Levels in Patients Underwent Curative-intent Hepatectomy For Colorectal Liver Metastases: A Two-Center Cohort Study

2021 ◽  
Author(s):  
Long Bai ◽  
Ze-Yu Lin ◽  
Yun-Xin Lu ◽  
Qin Chen ◽  
Han Zhou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lactate Dehydrogenase ◽  
Cancer Patients ◽  
Prognostic Value ◽  
Colorectal Liver Metastases ◽  
Validation Cohort ◽  
Curative Intent ◽  
Training Cohort ◽  
Preoperative Serum ◽  
Colorectal Cancer Patients

Abstract Background: The prognostic value of lactate dehydrogenase (LDH) in colorectal cancer patients has remained inconsistent between non-metastatic and metastatic settings. So far very few studies have included LDH in prognostic analysis for patients with colorectal liver metastases (CRLM) who underwent curative-intent hepatectomy. Patients and Methods: Consecutive metastatic colorectal cancer patients who underwent curative-intent resection for CRLM from two Chinese medical centers treated in 2000-2019 were enrolled in the training cohort (434 patients) and the validation cohort (146 patients). Overall survival (OS) was the primary endpoint. Cox regression model was performed to identify the prognostic values of LDH and other clinicopathology variables. A modification of the established Fong scoring system comprising LDH was developed within this Chinese population.Results: In the training cohort, preoperative LDH > upper limit of normal (ULN) was the strongest independent prognostic factor both for RFS (HR 2.11, 95% confidence intervals [CIs], 1.54-2.89; P < .001) and OS (HR 2.41, 95% CI, 1.72-3.39; P < .001) in multivariate analysis. 5-year survival rates were 23.7% and 52.9% in the LDH > ULN group and LDH < ULN group, respectively. These data were also confirmed in the validation cohort and then in pooled cohort. Replacing carcinoembryonic antigen (CEA) with LDH in the Fong score contributed to an improvement in the predictive value.Conclusions: Preoperative serum LDH is a reliable and independent predictor for curative-intent CRLM resection. Composite of LDH and Fong score is a potential stratification tool for CRLM resection.

scholarly journals Transcriptome of Tumor-Infiltrating T Cells in Colorectal Cancer Patients Uncovered a Unique Gene Signature in CD4+ T Cells Associated with Poor Disease-Specific Survival

Vaccines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 334
Author(s):  
Salman M. Toor ◽  
Varun Sasidharan Nair ◽  
Reem Saleh ◽  
Rowaida Z. Taha ◽  
Khaled Murshed ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
T Cell Activation ◽  
Cd4 T Cells ◽  
Poor Prognosis ◽  
Gene Signature ◽  
The Cancer Genome Atlas ◽  
Disease Specific Survival ◽  
Unique Gene ◽  
Disease Specific

Colorectal cancer (CRC) is influenced by infiltration of immune cell populations in the tumor microenvironment. While elevated levels of cytotoxic T cells are associated with improved prognosis, limited studies have reported associations between CD4+ T cells and disease outcomes. We recently performed transcriptomic profiling and comparative analyses of sorted CD4+ and CD8+ tumor-infiltrating lymphocytes (TILs) from bulk tumors of CRC patients with varying disease stages. In this study, we compared the transcriptomes of CD4+ with CD8+ TILs. Functional annotation pathway analyses revealed the downregulation of inflammatory response-related genes, while T cell activation and angiogenesis-related genes were upregulated in CD4+ TILs. The top 200 deregulated genes in CD4+ TILs were aligned with the cancer genome atlas (TCGA) CRC dataset to identify a unique gene signature associated with poor prognosis. Moreover, 69 upregulated and 20 downregulated genes showed similar trends of up/downregulation in the TCGA dataset and were used to calculate “poor prognosis score” (ppScore), which was significantly associated with disease-specific survival. High ppScore patients showed lower expression of Treg-, Th1-, and Th17-related genes, and higher expression of Th2-related genes. Our data highlight the significance of T cells within the TME and identify a unique candidate prognostic gene signature for CD4+ TILs in CRC patients.

scholarly journals Prognostic Impact of the Number of Examined Lymph Nodes in Stage II Colorectal Adenocarcinoma: A Retrospective Study

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Purun Lei ◽  
Ying Ruan ◽  
Jianpei Liu ◽  
Qixian Zhang ◽  
Xiao Tang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Stage Ii ◽  
Lymph Node Status ◽  
Stage Migration ◽  
Prognostic Impact ◽  
Disease Specific Survival ◽  
Stage Ii Colorectal Cancer ◽  
Disease Specific

Background. Evaluation of lymph node status is critical in colorectal carcinoma (CRC) treatment. However, as patients with node involvement may be incorrectly classified into earlier stages if the examined lymph node (ELN) number is too small and escape adjuvant therapy, especially for stage II CRC. The aims of this study were to assess the impact of the ELN on the survival of patients with stage II colorectal cancer and to determine the optimal number. Methods. Data from the US Surveillance, Epidemiology, and End Results (SEER) database on stage II resected CRC (1988-2013) were extracted for mathematical modeling as ELN was available since 1988. Relationship between ELN count and stage migration and disease-specific survival was analyzed by using multivariable models. The series of the mean positive LNs, odds ratios (ORs), and hazard ratios (HRs) were fitted with a LOWESS (Locally Weighted Scatterplot Smoothing) smoother, and the structural break points were determined by the Chow test. An independent cohort of cases from 2014 was retrieved for validation in 5-year disease-specific survival (DSS). Results. An increased ELN count was associated with a higher possibility of metastasis LN detection (OR 1.010, CI 1.009-1.011, p<0.001) and better DSS in LN negative patients (OR 0.976, CI 0.975-0.977, p<0.001). The cut-off point analysis showed a threshold ELN count of 21 nodes (HR 0.692, CI 0.667-0.719, p<0.001) and was validated with significantly better DSS in the SEER 2009 cohort CRC (OR 0.657, CI 0.522-0.827, p<0.001). The cut-off value of the ELN count in site-specific surgeries was analyzed as 20 nodes in the right hemicolectomy (HR 0.674, CI 0.638-0.713, p<0.001), 19 nodes in left hemicolectomy (HR 0.691, CI 0.639-0.749, p<0.001), and 20 nodes in rectal resection patients (HR 0.671, CI 0.604-0.746, p<0.001), respectively. Conclusions. A higher number of ELNs are associated with more-accurate node staging and better prognosis in stage II CRCs. We recommend that at least 21 lymph nodes be examined for accurate diagnosis of stage II colorectal cancer.

Cancer risk and overall survival in APC I1307K carriers.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1592-1592
Author(s):  
Stephen B. Gruber ◽  
Joseph D Bonner ◽  
Flavio Lejbkowicz ◽  
Stephanie Schmit ◽  
Hedy Rennert ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Confidence Interval ◽  
Molecular Epidemiology ◽  
Population Distribution ◽  
Lifetime Risk ◽  
Disease Specific Survival ◽  
Cancer Study ◽  
Apc I1307k ◽  
Disease Specific

1592 Background: The germline variant APC I1307K is one of the most commonly identified pathogenic variants on germline genetic testing panels. The purpose of the Molecular Epidemiology of Colorectal Cancer study was to quantify the risk of colorectal cancer among carriers, characterize the clinical, pathologic, and molecular features of colorectal cancers arising in patients with APC I1307K, and to describe the overall and disease-specific survival of carriers with colorectal cancer. Here, the final results of the Molecular Epidemiology of Colorectal Cancer Study are reported with respect to APC I1307K. Methods: We consented 6,006 incident, pathologically confirmed cases of colorectal adenocarcinoma and 5,023 age, sex, and ethnicity matched controls without colorectal cancer between March 31, 1998 and July 1, 2017 within a geographically defined area of Northern Israel. Comprehensive, in-person epidemiologic interviews were conducted for cases and controls, with uniform histopathologic review, detailed molecular analysis, medical record review and clinical follow-up for up to 21 years. Results: The demographic and clinical features of incident colorectal cancer cases matched the population distribution of colorectal cancer in Israel. APC I1307K was identified in 429 (7.1%) of cases and 201 (4.0%) of controls. The estimated relative risk of colorectal cancer among carriers was 1.89 (95% confidence interval, 1.59 - 2.24), p < 0.0001. The prevalence and odds ratios differed by ethnic group. Homozygous carriers were at especially high risk, with an odds ratio of 3.90 (95% confidence interval 1.11–13.71). APC I1307K carriers were significantly less likely to have microsatellite instable tumors (p = 0.04). Overall survival of APC I1307K carriers was not significantly different than survival of non-carriers, after adjustment for age, stage, sex, ethnicity, and microsatellite instability. Conclusions: APC I1307K is an actionable germline mutation that confers meaningful lifetime risk of colorectal cancer in heterozygous and homozygous carriers. APC I1307K is not an independent prognostic factor for overall survival or disease specific survival and is not associated with the MSI phenotype. Cumulative lifetime risk estimates inform genetic counseling and provide data for policies regarding the timing and frequency of screening and other preventive strategies.

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