Dataset Information

Different TERT Expression between Colorectal Adenoma and Serrated Polyp.

ABSTRACT: Background and Objectives: Telomere regulation have an association with colorectal cancer. Previous studies demonstrated its implication in colorectal carcinogenesis. This study aimed to identify the role of telomerase reverse transcriptase (TERT) in colorectal carcinogenesis and determine TERT expression and their associated genes in precancerous lesions. Materials and Methods: TERT expression in 93 colorectal precursor lesions was analyzed. This included 61 tubular adenomas (TAs) and 32 serrated polyps (SPs). Furthermore, KRAS and BRAF gene mutations and microsatellite instability were analyzed. Statistical tests were performed to analyze the relationship between variables. Results: TERT expression in TAs, when compared with those observed in paired adjacent nontumor tissues, was 0.92 ± 0.78. TERT expression levels were significantly lower in SPs (0.38 ± 0.14, p < 0.001). KRAS and BRAF mutations were mutually exclusive in TAs and SPs (p < 0.001). TERT expression tended to be associated with KRAS mutations (46.7% vs. 22.0%, p = 0.098) and low-grade tumors (35.0% vs. 16.0%, p = 0.096), but this difference was insignificant. Conclusions: TERT expression has a pivotal role in progression to TAs in colorectal tissue. Considering the association between TERT expression and KRAS mutation, therapeutic drugs targeting this pathway can be developed for cancer prevention.

SUBMITTER: Jung SJ

PROVIDER: S-EPMC7558296 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Different TERT Expression between Colorectal Adenoma and Serrated Polyp.

Jung Soo-Jung SJ Park Jae-Hee JH Hwang Ilseon I Lee Jae-Ho JH

Medicina (Kaunas, Lithuania) 20200911 9

<i>Background and Objectives:</i> Telomere regulation have an association with colorectal cancer. Previous studies demonstrated its implication in colorectal carcinogenesis. This study aimed to identify the role of telomerase reverse transcriptase (TERT) in colorectal carcinogenesis and determine TERT expression and their associated genes in precancerous lesions. <i>Materials and Methods:</i> TERT expression in 93 colorectal precursor lesions was analyzed. This included 61 tubular adenomas (TAs) ...[more]

PMID: 32932803

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Project description:Background and aimsApproximately 20%-30% of colorectal cancers (CRCs) arise from the serrated polyp pathway. CRC screening options have differential sensitivity to detect sessile serrated polyps (SSPs). We used the Colorectal Cancer and Adenoma Incidence and Mortality Microsimulation Model (CRC-AIM) to assess how the detection of SSPs impacts predicted life years gained (LYG), CRC incidence, and CRC mortality with multitarget stool DNA (mt-sDNA) or fecal immunochemical test (FIT) screening.MethodsA simulated cohort of average-risk US individuals underwent triennial mt-sDNA or annual FIT screening between ages 45-75 years. SSP-attributed CRCs were modeled at 0% (base case), 14.3%, 20%, and 30%, in combination with 4 adherence & attendance scenarios: S1: 100% stool-screening adherence/100% follow-up colonoscopy attendance after a positive stool test; S2: reported stool-screening adherence (mt-sDNA = 71%; FIT = 43%)/100% follow-up colonoscopy attendance; S3: reported stool-screening adherence/reported follow-up colonoscopy attendance (mt-sDNA = 72%; FIT = 47%); and S4: reported stool-screening adherence/72% follow-up colonoscopy attendance. Outcomes were per 1000 individuals. Sensitivity analyses used ranges of stool-screening adherence or follow-up attendance.ResultsAt S1, S2, S3, and S4, LYG with FIT at the base case (0% SSP-attributed CRC) was 346.7, 279.3, 126.6, and 196.1, respectively, and with mt-sDNA was 324.6, 311.8, 215.8, and 215.8, respectively. Among the 4 adherence/attendance scenarios, modeling SSP-attributed CRCs decreased LYG by 4.9-20.9 with FIT and 2.0-5.1 with mt-sDNA. At S3 and 30% SSP-attributable CRCs, mt-sDNA had 95.1 more LYG, 21.5% greater CRC incidence reduction, and 22.2% greater CRC mortality reduction than FIT.ConclusionIncorporating SSPs and real-world adherence into the CRC-AIM modeling analyses yielded more practice-relevant estimates of CRC screening outcomes and should be applied in future studies to afford more appropriate assessment of comparative effectiveness estimates between guideline-endorsed screening options.

Project description:Purpose To report the prevalence and characteristics of serrated polyps identified in a large, average-risk population undergoing screening computed tomographic (CT) colonography. Materials and Methods This HIPAA-compliant retrospective study was approved by the institutional review board of the University of Wisconsin School of Medicine and Public Health. The need for informed consent was waived. Nine thousand six hundred examinations from 8289 patients were enrolled in a single-institution CT colonography-based screening program (from 2004 to 2011) and were evaluated for the presence of nondiminutive serrated lesions and advanced adenomas. The prevalence and characteristics of these lesions were tabulated. Generalized estimating equation regressions of polyp characteristics that may contribute to visualization of serrated lesions were investigated, including polyp size, location, and morphologic appearance; histologic findings; and presence or absence of contrast material tagging. Results Nondiminutive serrated lesions (?6 mm) were seen at CT colonography-based screening with a prevalence of 3.1% (254 of 8289 patients). Sessile serrated adenomas (SSAs) and traditional serrated adenomas (TSAs) constituted 36.8% (137 of 372) and 4.3% (16 of 372) of serrated lesions, respectively; hyperplastic polyps (HPs) accounted for 58.9% (219 of 372 lesions). SSA and TSA tended to be large (mean size, 10.6 mm and 14.1 mm, respectively), with size categories and polyp subgroups significantly associated (P < .0001). SSA tended to be proximal in location (91.2%, 125 of 137 lesions) and flat in morphologic appearance (39.4%, 54 of 137 lesions) compared with TSA and HP. The presence of high-grade dysplasia in serrated lesions was uncommon when compared with advanced adenomas (one of 372 lesions vs 22 of 395 lesions, respectively; P < .0001). Multivariate analysis showed that contrast material tagging markedly improved serrated polyp detection with an odds ratio of 40.4 (95% confidence interval: 10.1, 161.4). Conclusion Serrated lesions are seen at CT colonography-based screening with a nondiminutive prevalence of 3.1%. These lesions tend to be large, flat, and proximal in location. Adherent contrast material coating on these polyps aids in their detection, despite an often flat morphologic appearance. (©) RSNA, 2016 Online supplemental material is available for this article.

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Different TERT Expression between Colorectal Adenoma and Serrated Polyp.

Publications

Different TERT Expression between Colorectal Adenoma and Serrated Polyp.

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