BackgroundColorectal cancer (CRC) is the second leading cause of cancer-related mortality in the United States. There is an increasing need for the identification of biomarkers of pre-malignant and early stage CRC to improve risk-stratification and screening recommendations. In this study, we investigated the possibility of metabolic and mitochondrial reprogramming early in the pre-malignant colorectal field.MethodsRectal biopsies were taken from 81 patients undergoing screening colonoscopy, and gene expression of metabolic and mitochondrial markers were assessed using real time quantitative PCR. Validation studies were performed in two different animal models of colon carcinogenesis: Pirc rats and AOM-treated rats.ResultsWe found evidence of a Warburg effect in the normal-appearing rectal mucosa of patients harboring precancerous lesions elsewhere in the colon compared to control patients, with a significant increase in HIF1a, SLC2A1 (referred to as GLUT1), PKM2, and LDHA. We also found evidence of early mitochondrial changes in the colorectal field of patients harboring pre-cancerous lesions, with significantly increased mitochondrial gene expression of DRP1 (fission), OPA1 (fusion), PGC1-a (biogenesis), UCP2 (uncoupling) and mtND1 (copy number). Similar results were observed in the two different animal models.ConclusionsThese results demonstrate for the first time evidence of early Warburg-like metabolic changes as well as changes in mitochondrial function, dynamics and mtDNA copy number in endoscopically normal premalignant colorectal mucosal field. These findings provide an opportunity for the development of metabolic biomarkers that could be used for improving screening recommendations and risk-stratification. This also provides a potential target for novel chemopreventive strategies in the pre-malignant colorectal field.
A community-based cross-sectional study was conducted in brothel-based sex workers of West Bengal, Eastern India, to determine their oncogenic human papillomavirus (HPV) status and the presence of pre-cancerous lesions. A total of 229 sex workers from three districts of West Bengal participated in the study. All the study participants were interviewed with the aid of a pre-tested questionnaire to determine their sociodemographics, risk behaviour and risk perceptions after obtaining informed verbal consent. The interview was followed by collection of cervical cells from all participants using a disposable vaginal speculum and cervical cytobrush. Oncogenic HPV DNA was detected by real-time polymerase chain reaction (PCR). A simultaneous Papanicolaou test ('Pap smear') was performed to detect cervical cytological abnormalities. Overall, the prevalence of oncogenic HPV was found to be 25% (58/229) among the studied population. A subset (n=112) of the sample was tested separately to determine the existence and magnitude of HPV genotypes 16 and 18. The results showed that genotype 16 was prevalent in 10% (11/112), genotype 18 in 7% (8/112) and both genotype 16 and 18 in 7% (8/112). The HPV prevalence rate showed a decreasing trend with age, being 71.4% in the 10-19 years age group, 32.3% in the 20-29 years age group, 18.3% in the 30-39 years age group and 2.5% in the >or=40 years age group (statistically significant differences, P
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