Telomere Length and Telomerase Activity in Subcutaneous and Visceral Adipose Tissues from Obese and Non-Obese Patients with and without Colorectal Cancer

Simple Summary The risk associated with obesity for the development of colorectal cancer seems to be well established. However, no biomarkers have been defined that allow the degree of obesity to be related to the clinical evolution of individuals affected by colorectal cancer. With the aim of contributing to the development of this correlation, we carried out a prospective study investigating parameters related to telomere function in the subcutaneous and visceral adipose tissues of a total of 147 subjects affected and not affected by colorectal cancer. Both the relative telomere length and the activity of telomerase in the adipose tissues seem to constitute parameters of interest in the clinical evaluation of individuals with colorectal cancer, which could be also related to the body mass index. Abstract To investigate the molecular mechanisms that link obesity and colorectal cancer (CRC), we analyzed parameters related to telomere function in subcutaneous and visceral adipose tissues (SAT and VAT), including subjects with and without CRC, who were classified according to their body mass index (BMI). Adipose tissues were obtained from 147 patients who had undergone surgery. A total of 66 cases corresponded to CRC patients, and 81 subjects were not affected by cancer. Relative telomere length was established by qPCR, and telomerase activity was determined by a method based on the telomeric repeat amplification protocol. Our results indicated longer telomeres in patients affected by CRC, both in SAT and VAT, when compared to the group of subjects without CRC. Tumor local invasion was associated with telomere length (TL) in SAT. Considering the BMI values, significant differences were found in the TL of both adipose tissues between subjects affected by CRC and those without cancer. Overweight subjects showed the greatest differences, with longer telomeres in the group of CRC patients, and a higher number of cases with telomerase reactivation in the VAT of subjects without cancer. In conclusion, parameters related to telomere function in adipose tissue could be considered as potential biomarkers in the evaluation of CRC and obesity.

[1]  M. Taheri,et al.  A Review on the Role of miR-1246 in the Pathoetiology of Different Cancers , 2022, Frontiers in Molecular Biosciences.

[2]  K. El-Hayek,et al.  Adipose-Derived Stem Cells, Obesity, and Inflammation , 2021, American journal of physical medicine & rehabilitation.

[3]  M. Todaro,et al.  Adipose stem cell niche reprograms the colorectal cancer stem cell metastatic machinery , 2021, Nature Communications.

[4]  D. O'Leary,et al.  Body Composition, Inflammation, and 5-Year Outcomes in Colon Cancer , 2021, JAMA network open.

[5]  A. Barabash,et al.  Obesity and telomere status in the prognosis of patients with colorectal cancer submitted to curative intention surgical treatment. , 2021, Molecular and clinical oncology.

[6]  K. Taniguchi,et al.  Inflammation-Induced Tumorigenesis and Metastasis , 2021, International journal of molecular sciences.

[7]  C. F. Nicoletti,et al.  The Impact of Gastric Bypass on Telomere Length and Shelterin Complex Gene Expression: 6 Months Prospective Study , 2021, Obesity Surgery.

[8]  A. Jemal,et al.  Cancer Statistics, 2021 , 2021, CA: a cancer journal for clinicians.

[9]  R. Dorajoo,et al.  Correlation of Telomere Length in Adipose Tissue and Leukocytes and its Association with Postsurgical Weight Loss , 2020, Obesity.

[10]  C. Friedenreich,et al.  Physical activity, obesity and sedentary behavior in cancer etiology: epidemiologic evidence and biologic mechanisms , 2020, Molecular oncology.

[11]  M. Monteiro,et al.  Impact of adiposity on staging and prognosis of colorectal cancer. , 2019, Critical reviews in oncology/hematology.

[12]  J. Meyerhardt,et al.  The Association of Abdominal Adiposity with Mortality in Patients with Stage I-III Colorectal Cancer. , 2019, Journal of the National Cancer Institute.

[13]  W. Renner,et al.  Subcutaneous adipose tissue distribution and telomere length , 2019, Clinical chemistry and laboratory medicine.

[14]  Fei Wang,et al.  Telomere and its role in the aging pathways: telomere shortening, cell senescence and mitochondria dysfunction , 2018, Biogerontology.

[15]  F. Siemers,et al.  Role of Wnt signaling during inflammation and sepsis: A review of the literature , 2018, The International journal of artificial organs.

[16]  C. Harris,et al.  Mutant p53 cancers reprogram macrophages to tumor supporting macrophages via exosomal miR-1246 , 2018, Nature Communications.

[17]  F. Berardinelli,et al.  Telomere Length Maintenance in Cancer: At the Crossroad between Telomerase and Alternative Lengthening of Telomeres (ALT) , 2018, International journal of molecular sciences.

[18]  A. Stier,et al.  Does oxidative stress shorten telomeres in vivo? A review , 2017, Biology Letters.

[19]  M. Ochani,et al.  Mitigation of sepsis-induced inflammatory responses and organ injury through targeting Wnt/β-catenin signaling , 2017, Scientific Reports.

[20]  G. Manic,et al.  Deciphering the loop of epithelial-mesenchymal transition, inflammatory cytokines and cancer immunoediting. , 2017, Cytokine & growth factor reviews.

[21]  D. Shibata,et al.  Quantitative Assessment of Visceral Obesity and Postoperative Colon Cancer Outcomes , 2017, Journal of Gastrointestinal Surgery.

[22]  F. Tinahones,et al.  Adipogenic Impairment of Adipose Tissue–Derived Mesenchymal Stem Cells in Subjects With Metabolic Syndrome: Possible Protective Role of FGF2 , 2016, The Journal of clinical endocrinology and metabolism.

[23]  M. Goldberg,et al.  Tumor cells derived exosomes contain hTERT mRNA and transform nonmalignant fibroblasts into telomerase positive cells , 2016, Oncotarget.

[24]  A. Sánchez-Pernaute,et al.  Clinical Relevance of Telomere Status and Telomerase Activity in Colorectal Cancer , 2016, PloS one.

[25]  J. García-Foncillas,et al.  Obesity and colorectal cancer: molecular features of adipose tissue , 2016, Journal of Translational Medicine.

[26]  Jürgen Böhm,et al.  Metabolomics and transcriptomics identify pathway differences between visceral and subcutaneous adipose tissue in colorectal cancer patients: the ColoCare study. , 2015, The American journal of clinical nutrition.

[27]  M. Stumvoll,et al.  Telomere length differences between subcutaneous and visceral adipose tissue in humans. , 2015, Biochemical and biophysical research communications.

[28]  Naoto Tsuchiya,et al.  Circulating Exosomal microRNAs as Biomarkers of Colon Cancer , 2014, PloS one.

[29]  V. Mohan,et al.  Convergence of adipocyte hypertrophy, telomere shortening and hypoadiponectinemia in obese subjects and in patients with type 2 diabetes. , 2012, Clinical biochemistry.

[30]  J. Moreno-Navarrete,et al.  Telomere length of subcutaneous adipose tissue cells is shorter in obese and formerly obese subjects , 2010, International Journal of Obesity.

[31]  R. Cawthon.  Telomere measurement by quantitative PCR. , 2002, Nucleic acids research.

[32]  N. Blin,et al.  A general method for isolation of high molecular weight DNA from eukaryotes. , 1976, Nucleic acids research.

[33]  F. R. Watson,et al.  Cancer of the colon: the influence of the no-touch isolation technic on survival rates. , 1967, Annals of surgery.

[34]  M. Giardini,et al.  Telomere and telomerase biology. , 2014, Progress in molecular biology and translational science.