Diabetes, Obesity, and the Metabolic Syndrome as Prognostic Factors in Stages I to III Colorectal Cancer Patients

Croft, Brianna; Reed, Melissa; Patrick, Caitlyn; Kovacevich, Natalie; Voutsadakis, Ioannis A.

doi:10.1007/s12029-018-0056-9

Cited by 31 publications

(32 citation statements)

References 26 publications

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“…Moreover, emerging evidence from observational studies and meta-analyses suggest that diabetes mellitus is associated with an increased risk of cancer, as well as cancer incidence or prognosis (Noto, 2018). In particular, diabetes has been validated as a prognostic factor in stages I to III colorectal cancer patients (Croft et al, 2018), in which GAD2 involved could induce β-cell death. Other cancer-associated processes or pathways and literature evidence for the occurrence or development of colon cancer can be found in Table 1.…”

Section: Ppi Network and Pathway Integration Analysis Of Survival-assmentioning

confidence: 99%

Detecting Prognosis Risk Biomarkers for Colon Cancer Through Multi-Omics-Based Prognostic Analysis and Target Regulation Simulation Modeling

et al. 2020

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Background: Colon cancer is one of the most common health threats for humans since its high morbidity and mortality. Detecting potential prognosis risk biomarkers (PRBs) is essential for the improvement of therapeutic strategies and drug development. Currently, although an integrated prognostic analysis of multi-omics for colon cancer is insufficient, it has been reported to be valuable for improving PRBs' detection in other cancer types. Aim: This study aims to detect potential PRBs for colon adenocarcinoma (COAD) samples through the cancer genome atlas (TCGA) by integrating muti-omics. Materials and Methods: The multi-omics-based prognostic analysis (MPA) model was first constructed to systemically analyze the prognosis of colon cancer based on four-omics data of gene expression, exon expression, DNA methylation and somatic mutations on COAD samples. Then, the essential features related to prognosis were functionally annotated through protein-protein interaction (PPI) network and cancerrelated pathways. Moreover, the significance of those essential prognostic features were further confirmed by the target regulation simulation (TRS) model. Finally, an independent testing dataset, as well as the single cell-based expression dataset were utilized to validate the generality and repeatability of PRBs detected in this study. Results: By integrating the result of MPA modeling, as well the PPI network, integrated pathway and TRS modeling, essential features with gene symbols such as EPB41,

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Section: Ppi Network and Pathway Integration Analysis Of Survival-assmentioning

confidence: 99%

Detecting Prognosis Risk Biomarkers for Colon Cancer Through Multi-Omics-Based Prognostic Analysis and Target Regulation Simulation Modeling

et al. 2020

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“…The association between type 2 diabetes mellitus (T2DM) and colon cancer (CC) has been extensively discussed (Gonz alez et al, 2017). While several cohort studies and meta-analyses have reported an increased risk for CC development in T2DM patients (Larsson et al, 2005;Sun and Yu, 2012) as well as a higher short-and long-term mortality (Croft et al, 2018;Zhu et al, 2017), others identified biases produced by the size and origin of the populations studied (de Jong et al, 2017;Tsilidis et al, 2015). Our own experience using a highly homogeneous Spanish cohort indicated that even if there is a higher risk of cancer development, the effect of diabetes does not entail a worse outcome once the tumor has developed .…”

Section: Introductionmentioning

confidence: 99%

Molecular evidence of field cancerization initiated by diabetes in colon cancer patients

et al. 2019

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The potential involvement of type 2 diabetes mellitus (T2 DM ) as a risk factor for colon cancer ( CC ) has been previously reported. While several clinical studies show a higher incidence of CC and a lower survival rate in diabetics, others report no association. Our own experience indicates that diabetes does not seem to worsen the prognosis once the tumor is present. Despite this controversy, there are no wide‐spectrum molecular studies that delve into the impact of T2 DM ‐related mechanisms in colon carcinogenesis. Here, we present a transcriptomic and proteomic profiling of paired tumor and normal colon mucosa samples in a cohort of 42 CC patients, 23 of which have T2 DM . We used gene set enrichment and network approaches to extract relevant pathways in diabetics, referenced them to current knowledge, and tested them using in vitro techniques. Through our transcriptomics approach, we identified an unexpected overlap of pathways overrepresented in diabetics compared to nondiabetics, in both tumor and normal mucosa, including diabetes‐related metabolic and signaling processes. Proteomic approaches highlighted several cancer‐related signaling routes in diabetics found only in normal mucosa, not in tumors. An integration of the transcriptome and proteome analyses suggested the deregulation of key pathways related to colon carcinogenesis which converged on tumor initiation axis TEAD / YAP ‐ TAZ as a potential initiator of the process. In vitro studies confirmed upregulation of this pathway in nontumor colon cells under high‐glucose conditions. In conclusion, T2 DM associates with deregulation of cancer‐related processes in normal colon mucosa adjacent to tissue which has undergone a malignant transformation. These data support that in diabetic patients, the local microenvironment in normal colon mucosa may be a factor driving field cancerization promoting carcinogenesis. Our results set a new framework to study links between diabetes and colon cancer, including a new role of the TEAD / YAP ‐ TAZ complex as a potential driver.

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“…Optimal cut-off values of the lipid indices by sex. CRC (30,31). A meta-analysis of 16 studies indicated that high levels of TG increased the overall risk of cancer by 20% (32).…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of high triglyceride and apolipoprotein B levels in patients with stage III and high-risk stage II colorectal cancer undergoing curative surgery

Chen

Liu

et al. 2020

Oncol Lett

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Although epidemiologic studies suggest that dyslipidemia increases the risk of colorectal cancer (CRC), the prognostic value of blood lipid and apolipoprotein levels in CRC remains unclear. The aim of the present study was to investigate the impact of blood lipid and apolipoprotein levels on the prognosis of patients with stage III and high-risk stage II CRC undergoing curative surgery. Preoperative levels of total cholesterol, triglycerides (TG), high-density lipoprotein, low-density lipoprotein, very-low-density lipoprotein, apolipoprotein A1 and apolipoprotein B (APO-B) in patients with CRC undergoing surgery were evaluated. The cutoff values of these factors were determined by the maximal x 2 method and were used to classify patients into two prognostic groups: Poor and good prognosis groups. The patients' prognostic values were assessed using the Kaplan-Meier curve and Cox regression analysis. In addition, the impact of these parameters on the prognosis and their predictive accuracy were evaluated using nomograms and Harrell's concordance index, respectively. In total, 246 patients were included in this evaluation. Based on the cutoff points for TG (1.53 mmol/l in men and 1.58 mmol/l in women) and APO-B (0.73 mmol/l in men and women), the present study determined that both TG and APO-B were predictors of disease-free survival (DFS) and overall survival (OS). Multivariate analysis demonstrated that high TG (men, ≥1.53 mmol/l; women, ≥1.58 mmol/l) and high APO-B (≥0.73 mmol/l) levels were significantly associated with decreased DFS and OS. Nomograms that included values for TG and APO-B levels demonstrated higher predictive accuracy compared with that of nomograms without these values. These results indicated that TG and APO-B levels may be good independent prognostic biomarkers after radical CRC surgery. Therefore, adjusting these parameters to moderate levels may be beneficial.

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Diabetes, Obesity, and the Metabolic Syndrome as Prognostic Factors in Stages I to III Colorectal Cancer Patients

Abstract: These data pinpoint to diabetes mellitus (DM) as a possible prognostic factor for PFS in localized colorectal cancer and further cast doubt for the value of obesity as measured by body mass index (BMI) on local stage colorectal cancer prognosis.

Cited by 31 publications

References 26 publications

Detecting Prognosis Risk Biomarkers for Colon Cancer Through Multi-Omics-Based Prognostic Analysis and Target Regulation Simulation Modeling

Detecting Prognosis Risk Biomarkers for Colon Cancer Through Multi-Omics-Based Prognostic Analysis and Target Regulation Simulation Modeling

Molecular evidence of field cancerization initiated by diabetes in colon cancer patients

Prognostic significance of high triglyceride and apolipoprotein B levels in patients with stage III and high-risk stage II colorectal cancer undergoing curative surgery

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