Should smokers be considered a high-risk group for colorectal cancer?

2004 ◽  
Vol 36 (10) ◽  
pp. 643-645 ◽  
Author(s):  
E. Giovannucci
2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15565-e15565
Author(s):  
Qiqi Zhu ◽  
Du Cai ◽  
Wei Wang ◽  
Min-Er Zhong ◽  
Dejun Fan ◽  
...  

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.


2013 ◽  
Vol 60 (2) ◽  
Author(s):  
Zoran Stojcev ◽  
Tomasz Banasiewicz ◽  
Michał Kaszuba ◽  
Adam Sikorski ◽  
Marek Szczepkowski ◽  
...  

Detection of mutations in families with a hereditary predisposition to colon cancer gives an opportunity to precisely define the high-risk group. 36 patients operated on for colon cancer, with familiar prevalence of this malignancy, were investigated using the DNA microarrays method with the potential detection of 170 mutations in MLH1, MSH2, MSH6, CHEK2, and NOD2 genes. In microarrays analysis of DNA in 9 patients (25% of the investigated group), 6 different mutations were found. The effectiveness of genetic screening using the microarray method is comparable to the effectiveness of other, much more expensive and time-consuming methods.


Author(s):  
Dongyan Zhao ◽  
Xizhen Sun ◽  
Sidan Long ◽  
Shukun Yao

AbstractAimLong non-coding RNAs (lncRNAs) have been identified to regulate cancers by controlling the process of autophagy and by mediating the post-transcriptional and transcriptional regulation of autophagy-related genes. This study aimed to investigate the potential prognostic role of autophagy-associated lncRNAs in colorectal cancer (CRC) patients.MethodsLncRNA expression profiles and the corresponding clinical information of CRC patients were collected from The Cancer Genome Atlas (TCGA) database. Based on the TCGA dataset, autophagy-related lncRNAs were identified by Pearson correlation test. Univariate Cox regression analysis and the least absolute shrinkage and selection operator analysis (LASSO) Cox regression model were performed to construct the prognostic gene signature. Gene set enrichment analysis (GSEA) was used to further clarify the underlying molecular mechanisms.ResultsWe obtained 210 autophagy-related genes from the whole dataset and found 1187 lncRNAs that were correlated with the autophagy-related genes. Using Univariate and LASSO Cox regression analyses, eight lncRNAs were screened to establish an eight-lncRNA signature, based on which patients were divided into the low-risk and high-risk group. Patients’ overall survival was found to be significantly worse in the high-risk group compared to that in the low-risk group (log-rank p = 2.731E-06). ROC analysis showed that this signature had better prognostic accuracy than TNM stage, as indicated by the area under the curve. Furthermore, GSEA demonstrated that this signature was involved in many cancer-related pathways, including TGF-β, p53, mTOR and WNT signaling pathway.ConclusionsOur study constructed a novel signature from eight autophagy-related lncRNAs to predict the overall survival of CRC, which could assistant clinicians in making individualized treatment.


Endoscopy ◽  
2017 ◽  
Vol 50 (02) ◽  
pp. 119-127 ◽  
Author(s):  
Irina Gessl ◽  
Elisabeth Waldmann ◽  
Martha Britto-Arias ◽  
Daniela Penz ◽  
Eleonore Pablik ◽  
...  

Abstract Background and study aim The European guidelines for quality assurance in colorectal cancer screening and diagnosis contain postpolypectomy surveillance recommendations. They recommend follow-up intervals depending on the findings at index colonoscopy, and divide patients into a low-, intermediate- or high-risk group. The aim of this study was to assess the adherence of Austrian endoscopists to the European guidelines and to determine whether sending a reminder letter resulted in better adherence. Methods A single reminder letter containing the guidelines was sent to all endoscopists who participated in the Certificate of Quality for Screening Colonoscopy program in Austria. Adherence was assessed before and after the letter had been sent. Factors associated with adherence were investigated. Results We found poor baseline adherence to the guidelines. After the reminder letter, the adherence slightly improved in the low-risk group, but did not change in the intermediate-risk or high-risk groups. An adenoma detection rate of at least 20 % was associated with higher adherence rates. Generally, internists and hospitals showed better adherence compared with surgeons and private practices, respectively, both before and after the reminder letter. Conclusion A single reminder letter was not enough to improve the poor adherence to the European postpolypectomy surveillance guidelines. Thus, future studies are required to identify and eliminate all factors responsible for nonadherence to postpolypectomy guidelines in order to reach the goal of a safe, effective, and cost-effective colorectal cancer prevention tool in the near future.


2020 ◽  
Vol 27 (5) ◽  
Author(s):  
G. Nogueira-Costa ◽  
I. Fernandes ◽  
R. Gameiro ◽  
J. Gramaça ◽  
A.T. Xavier ◽  
...  

Introduction Inflammation is a critical component in carcinogenesis. The neutrophil-to-lymphocyte ratio (nlr) has been retrospectively studied as a biomarker of prognosis in metastatic colorectal cancer (mcrc). Compared with a low nlr, a high nlr is associated with worse prognosis. In the present study, we compared real-world survival for patients with mcrc based on their nlr group, and we assessed the utility of the nlr in determining first-line chemo­therapy and metastasectomy benefit. Methods In this retrospective and descriptive analysis of patients with mcrc undergoing first-line chemotherapy in a single centre, the last systemic absolute neutrophil and lymphocyte count before treatment was used for the nlr. A receiver operating characteristic curve was used to estimate the nlr cut-off value, dividing the patients into low and high nlr groups. Median overall survival (mos) was compared using Kaplan–Meier curves and the log-rank test. A multivariate analysis was performed using a Cox regression model. Results The 102 analyzed patients had a median follow-up of 15 months. Regardless of systemic therapy, approx­imately 20% of patients underwent metastasectomy. The nlr cut-off was established at 2.35, placing 45 patients in the low-risk group (nlr < 2.35) and 57 in the high-risk group (nlr ≥ 2.35). The Kaplan–Meier analysis showed a mos of 39.1 months in the low-risk group and 14.4 months in the high-risk group (p < 0.001). Multivariate Cox regression on the nlr estimated a hazard ratio of 3.08 (p = 0.01). Survival analysis in each risk subgroup, considering the history of metastasectomy, was also performed. In the low-risk group, mos was longer for patients undergoing metastasectomy than for those not undergoing the procedure (95.2 months vs. 22.6 months, p = 0.05). In the high-risk group, mos was not statistically different for patients undergoing or not undergoing metastasectomy (24.3 months vs. 12.7 months, p = 0.08). Conclusions Our real-world data analysis of nlr in patients with mcrc confirmed that this biomarker is useful in predicting survival. It also suggests that nlr is an effective tool to choose first-line treatment and to predict the benefit of metastasectomy.


2000 ◽  
Vol 33 (4) ◽  
pp. 512-516
Author(s):  
Katsuyuki Kunieda ◽  
Hisashi Kohmura ◽  
Jun Sano ◽  
Kazuya Yamaguchi ◽  
Shinichiro Aoki ◽  
...  

2021 ◽  
Author(s):  
Jianxin Li ◽  
Ting Han ◽  
Xin Wang ◽  
Yinchun Wang ◽  
Qingqiang Yang

Abstract Background Long non-coding RNA (lncRNA) is an important regulator of gene expression and serves fundamental role in immune regulation. The present study aimed to develop a novel immune-related lncRNA signature to accurately assess the prognosis of patients with colorectal cancer (CRC). Methods Transcriptome data and clinical information of patients with CRC were downloaded from The Cancer Genome Atlas (TCGA), and the immune-related mRNAs were extracted from immunomodulatory gene datasets IMMUNE RESPONSE and IMMUNE SYSTEM PROCESS based on the Molecular Signatures Database (MSigDB). Then, the immune-related lncRNAs were identified by a correlation analysis between immune-related mRNAs and lncRNAs. Subsequently, univariate, lasso and multivariate Cox regression were used to identify an immune-related lncRNA signature in training cohort, and the predict ability of the signature was further confirmed in the testing cohort and the entire TCGA cohort. Finally, the lncRNA-mRNA co-expression network was established to explore the biological role of the immune-related lncRNA signature. Results In total, 272 Immune-related lncRNAs were identified, five of which were applied to construct an immune-related lncRNA signature based on univariate, lasso and multivariate Cox regression analyses. The signature divided patients with CRC into low- and high-risk groups, and patients with CRC in high-risk group had poorer overall survival than those in low-risk group. Univariate and multivariate Cox regression analyses confirmed that the signature could be an independent prognostic factor in human CRC. Furthermore, functional enrichment analysis revealed that the immune-related lncRNA signature was significantly enriched in immune process and tumor classical pathways. Conclusions The present study revealed that the novel immune-related lncRNA signature could be exploited as underlying molecular biomarkers and therapeutic targets for the patients with CRC.


2022 ◽  
Author(s):  
Cong Zhang ◽  
Cailing Zeng ◽  
Shaoquan Xiong ◽  
Zewei Zhao ◽  
Guoyu Wu

Abstract Background: Colorectal cancer (CRC) is a heterogeneous disease and one of the most common malignancies in the world. Previous studies have found that mitophagy plays an important role in the progression of colorectal cancer. This study is aimed to investigate the relationship between mitophagy-related genes and the prognosis of patients with CRC.Methods: Gene expression profiles and clinical information of CRC patients were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Univariate Cox regression and the least absolute shrinkage and selection operator (LASSO) regression analysis were used to establish the prognostic signature composed of mitophagy related genes. Kaplan-Meier curve and receiver operating characteristic (ROC) curve were used to analyze patient survival and verify the predictive accuracy of the signature, respectively. Construction of a nomogram prognostic prediction model was based on risk scores and clinicopathological parameters. Using the Genomics of Drug Sensitivity in Cancer (GDSC) database and Tumor Immune Dysfunction and Exclusion (TIDE) algorithm to estimate the sensitivity of chemotherapy, targeted therapy and immunotherapy. Results: A total of 44 mitophagy-driven genes connected with CRC survival were identified, and prognostic signature was established based on the expression of 10 of them (AMBRA1, ATG14, MAP1LC3A, MAP1LC3B, OPTN, VDAC1, ATG5, CSNK2A2, MFN1, TOMM22). Patients were divided into high-risk and low-risk groups based on the median risk score, and the survival of patients in the high-risk group was significantly shorter than that of the low-risk group among the TCGA cohort (median OS 67.3 months vs not reached, p=0.00059) and two independent cohorts from GEO (median OS in GSE17536: 54.0 months vs not reached, p=0.0082; in GSE245: 7.7 months vs not reached, p=0.025). ROC curve showed that the area under the curves (AUC) of 1-, 3- and 5-year survival were 0.66, 0.66 and 0.64, respectively. Multivariate Cox regression analysis confirmed the independent prognostic value of the signature. Then we constructed a nomogram combining the risk score, age and M stage, which had a concordance index of survival prediction of 0.77 (95% CI=0.71-0.83) and more robust predictive sensitivity and specificity. Results showed that CD8+ T cells, regulatory T cells and activated NK cells were significantly more abundant in the high-risk group. Furthermore, patients in the high-risk group were more sensitive to potential targeted therapies, including Motesanib, ATRA, Olaparib, Selumetinib, AZD8055 and immunotherapy. Conclusion: In conclusion, we constructed and validated a novel mitophagy related gene signature that can be used as an independent prognostic biomarker for CRC, and may lead to better stratification and selection of precise treatment for CRC patients.


2019 ◽  
Vol 59 (1) ◽  
pp. 55-59 ◽  
Author(s):  
Athanasios Tampakis ◽  
Ekaterini Christina Tampaki ◽  
Afroditi Nonni ◽  
Gerasimos Tsourouflis ◽  
Alberto Posabella ◽  
...  

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