Advanced Colorectal Adenoma Research Articles

Alterations of Gut Microbiome in Patients with Colorectal Advanced Adenoma by Metagenomic Analyses.

Colorectal cancer (CRC) is one of the deadliest cancers worldwide, mostly arising from adenomatous polyps. Mounting evidence has demonstrated that changes in the gut microbiome play key roles in CRC progression, while quite few studies focused on the altered microbiota architecture of advanced adenoma (AA), a crucial precancerous stage of CRC. Thus, we aimed to investigate the microbial profiles of AA patients. Fecal samples were collected from 26 AA patients and 26 age- and sex-matched normal controls (NC), and analyzed by shotgun metagenomic sequencing. Gut microbial dysbiosis was observed in AA patients with lower alpha diversity. Advanced adenoma was characterized by an increased Bacillota/Bacteroidota ratio and higher Pseudomonadota levels compared to normal individuals. Linear discriminant analysis effect size (LEfSe) analysis was performed and identified 14 microbiota with significantly different abundance levels between AA and NC groups. Functional analysis revealed that tryptophan metabolism was upregulated in AA. Correspondingly, the expressions of gut microbes implicated in tryptophan metabolism also changed, including Akkermansia muciniphila, Bacteroides ovatus, Clostridium sporogenes, and Limosilactobacillus reuteri. The microbial network suggested that AA exhibited decreased correlation complexity, with Escherichia coli and Enterobacteriaceae unclassified harboring the strongest connectivity. A diagnostic model consisting of 3 microbial species was established based on random forest, yielding an area under the curve (AUC) of 0.799. Our study profiled the alterations of the gut microbiome in AA patients, which may enrich the knowledge of microbial signatures along with colorectal tumorigenesis and provide promising biomarkers for AA diagnosis.

A novel index combining fecal immunochemical test, DNA test, and age improves detection of advanced colorectal adenoma.

Although the fecal immunochemical test for hemoglobin (FIT) is a widely used screening test for colorectal cancer, it is not sensitive enough to detect advanced colorectal adenoma. To address this issue, we performed this study to investigate whether combining the FIT and fecal DNA testing of methylated somatostatin (SST) could improve diagnostic performance for advanced colorectal adenoma. We collected feces from 79 healthy subjects with negative results on colonoscopy, 43 patients with non-advanced colorectal adenoma, 117 patients with advanced colorectal adenoma, and 126 patients with colorectal cancer. After fecal DNA was incubated with methylation-sensitive restriction enzymes, SST methylation levels were measured by droplet digital PCR. Using logistic multivariate analysis, we established a prediction formula for detecting colorectal neoplasia and named it the FAMS (FIT, age, methylated SST) index. The diagnostic performance of a single use of FIT for advanced colorectal adenoma showed a sensitivity of 29.1% (34/117) and specificity of 89.3% (109/122). In contrast, the FAMS index showed a sensitivity of 56.4% (66/117) at a similar specificity point of 91.0% (111/122). Furthermore, even at the higher specificity point of 94.3% (115/122), the sensitivity was still higher than that of FIT, reaching 42.7% (50/117). As the FAMS index showed better diagnostic performance for advanced colorectal adenoma than a single use of FIT, the FAMS index could be a promising tool for detecting advanced colorectal adenoma.

A multi-center study for colorectal cancer early detection among patients with high-risk disease using a cell-free fragmentomics assay.

3613 Background: Colorectal cancer (CRC) is the third most prevalent and the second deadliest cancer globally, accounting for an estimated 1,926,000 new cases and 903,800 deaths in the year 2022 alone. It's also established that chronic inflammatory conditions, such as Crohn's disease and ulcerative colitis, elevate the risk of developing CRC. Therefore, a timely CRC diagnosis for patients with colorectal disease can significantly improve their prognosis and therefore reduce cancer-related mortalities. Methods: In this study, we enrolled a total of 167 patients diagnosed with CRC (stages I: 43, II: 55, III: 56, IV: 13) and 217 patients with benign colorectal disease (BCD), from five participating hospitals. All participants underwent colonoscopy procedures, and their CRC or BCD status was pathologically confirmed. The development of the cancer detection model was based on a training cohort of 98 CRC patients and 131 BCD patients from three hospitals, and the evaluation of the model's performance was carried out on an independent test cohort comprising 69 CRC patients and 96 BCD patients from the remaining two hospitals. The predictive model leveraged cell-free fragmentomics profiling, employing low-pass whole-genome sequencing (WGS) on pre-operative plasma samples to identify CRC. Results: The early detection model exhibited remarkable efficacy in differentiating CRC patients from those with BCD, achieving an Area Under the Curve (AUC) of 0.930 in the training cohort and a nearly equivalent AUC of 0.926 in the independent test cohort. By applying the same cutoff determined in the training cohort, our model demonstrated a high sensitivity (91.8% in the training cohort and 91.3% in the test cohort) and a satisfactory specificity (78.6% in the training cohort and 82.3% in the test cohort). Notably, the model showed consistent and robust performance across various CRC characteristics, including tumor location, histology subtypes, grades, and mismatch repair deficiency status in both cohorts. Moreover, our model outperformed traditional CRC screening methods such as the fecal immunochemical test, carcinoembryonic antigen (CEA), and CA19-9, which achieved AUCs of 0.742, 0.720, and 0.543, respectively. Further validation was conducted using an additional cohort of 31 patients with advanced colorectal adenoma (advCRA), where the model achieved an AUC of 0.846 and a 66.7% sensitivity for distinguishing advCRA from BCD. Conclusions: The study introduces a non-invasive, cell-free fragmentomics assay that incorporates low-pass WGS and machine learning algorithms, demonstrating significant clinical potential in accurately distinguishing CRC and BCD patients. Our innovative approach offers a promising alternative to traditional screening methods that can improve early CRC detection, enhance CRC patient outcomes, and reduce mortality rates.

Elucidating immunological characteristics of the adenoma-carcinoma sequence in colorectal cancer patients in South Korea using a bioinformatics approach

Colorectal cancer (CRC) is one of the top five most common and life-threatening malignancies worldwide. Most CRC develops from advanced colorectal adenoma (ACA), a precancerous stage, through the adenoma-carcinoma sequence. However, its underlying mechanisms, including how the tumor microenvironment changes, remain elusive. Therefore, we conducted an integrative analysis comparing RNA-seq data collected from 40 ACA patients who visited Dongguk University Ilsan Hospital with normal adjacent colons and tumor samples from 18 CRC patients collected from a public database. Differential expression analysis identified 21 and 79 sequentially up- or down-regulated genes across the continuum, respectively. The functional centrality of the continuum genes was assessed through network analysis, identifying 11 up- and 13 down-regulated hub-genes. Subsequently, we validated the prognostic effects of hub-genes using the Kaplan–Meier survival analysis. To estimate the immunological transition of the adenoma-carcinoma sequence, single-cell deconvolution and immune repertoire analyses were conducted. Significant composition changes for innate immunity cells and decreased plasma B-cells with immunoglobulin diversity were observed, along with distinctive immunoglobulin recombination patterns. Taken together, we believe our findings suggest underlying transcriptional and immunological changes during the adenoma-carcinoma sequence, contributing to the further development of pre-diagnostic markers for CRC.

Exogenous Insulin Therapy Is Associated with the Risk of Advanced Colorectal Adenoma in Patients with Diabetes Mellitus.

Exogenous insulin therapy increases systemic exposure to insulin which may promote the development of colorectal neoplasia. We sought to evaluate the association between exogenous insulin therapy and the incidence of advanced adenoma in type 2 diabetes mellitus. A retrospective cohort study was conducted from January 1, 2007, to January 1, 2018, in a regional health system serving the United States Philadelphia metropolitan area, Central New Jersey, and South Central Pennsylvania. Study patients consisted of a random sample of patients with type 2 diabetes mellitus aged 40-80years who had undergone two rounds of colonoscopy examinations. The exposure was cumulative duration of insulin therapy (i.e., no use, 1-365days and > 365days). The outcome was time to incident advanced adenoma. Of the 975 eligible patients, 184 patients accumulated > 365days of insulin therapy before the follow-up colonoscopy. The mean (standard deviation) duration between the two rounds of colonoscopy examination was 5.1 (2.9) years among the insulin users and 5.3 (3.9) years among non-users. Compared to no insulin exposure, receiving > 365days of insulin therapy was associated with an increased incidence of advanced adenoma (adjusted hazard ratio [aHR] 4.84, 95% confidence interval [CI] 2.82-8.30), right-sided advanced adenoma (aHR 5.48, 95% CI 2.90-10.35), and 3 or more adenomas (aHR 2.61, 95% CI 1.46-4.69) at the follow-up colonoscopy examination. Insulin therapy is associated with an increased risk of advanced adenoma and may serve as a novel risk-stratification factor to enhance the efficiency of existing colorectal cancer screening and surveillance programs.

Machine learning-based identification of colorectal advanced adenoma using clinical and laboratory data: a phase I exploratory study in accordance with updated World Endoscopy Organization guidelines for noninvasive colorectal cancer screening tests.

The recent World Endoscopy Organization (WEO) guidelines now recognize precursor lesions of colorectal cancer (CRC) as legitimate screening targets. However, an optimal screening method for detecting advanced adenoma (AA), a significant precursor lesion, remains elusive. We employed five machine learning methods, using clinical and laboratory data, to develop and validate a diagnostic model for identifying patients with AA (569 AAs vs. 3228 controls with normal colonoscopy). The best-performing model was selected based on sensitivity and specificity assessments. Its performance in recognizing adenoma-carcinoma sequence was evaluated in line with guidelines, and adjustable thresholds were established. For comparison, the Fecal Occult Blood Test (FOBT) was also selected. The XGBoost model demonstrated superior performance in identifying AA, with a sensitivity of 70.8% and a specificity of 83.4%. It successfully detected 42.7% of non-advanced adenoma (NAA) and 80.1% of CRC. The model-transformed risk assessment scale provided diagnostic performance at different positivity thresholds. Compared to FOBT, the XGBoost model better identified AA and NAA, however, was less effective in CRC. The XGBoost model, compared to FOBT, offers improved accuracy in identifying AA patients. While it may not meet the recommendations of some organizations, it provides value for individuals who are unable to use FOBT for various reasons.

The Association between Red Meat Consumption and Advanced Colorectal Adenomas in a Population Undergoing a Screening-Related Colonoscopy in Alberta, Canada

The association between red meat consumption and colorectal cancer has been rigorously examined. However, a more comprehensive understanding of how the intake of unprocessed red meat contributes to the development of early precancerous colorectal lesions, such as advanced colorectal adenomas (ACRAs), requires further investigation. We examined the associations between different types of red meat intake and ACRAs in a sample population of 1083 individuals aged ≥ 50 years undergoing an initial screening colonoscopy in Calgary, Alberta, Canada. Associations between grams per day of total, processed, and unprocessed red meat from diet history questionnaires and ACRAs were evaluated with multivariable logistic regression models. We also applied cubic spline models fitted with three knots (10th, 50th, and 90th percentiles) to identify potential nonlinear associations. We did not observe a meaningful association between unprocessed red meat intake and the presence of ACRAs. In contrast, for every 10 g/d increase in total and processed meat intake, we observed an increase in the odds of ACRAs at the screening colonoscopy (adjusted odds ratio (OR) = 1.05, 95% [CI = 1.01–1.09], p = 0.04) and (adjusted OR = 1.11, 95% [CI = 1.02–1.20], p = 0.02), respectively. This study highlights the importance of differentiating between types of red meat consumption in the context of dietary risks associated with ACRAs.

P665 Statins use and the risk of colorectal cancer in patients with inflammatory bowel disease: A Systematic review and meta-analysis

Abstract Background Statin use has been linked to a reduced risk of advanced colorectal adenomas; however, its association with colitis-associated dysplasia and cancer is not well-defined. We aimed to perform a systematic review and meta-analysis to assess the pooled association of statin exposure with dysplasia and colorectal cancer in patients with inflammatory bowel disease (IBD). Methods We searched MEDLINE, EMBASE, and the COCHRANE library to identify full text articles analyzing the risk of CRC or dysplasia development based on statin use in patients with IBD. A meta-analysis was performed using a random-effects model to pool estimates and report hazard ratios [HRs] or odds ratios [ORs], following the data format specified in the individual studies. Results A total of 4 studies were identified as eligible for the meta-analysis. In the analysis of studies presented with time-to-event outcomes, statin use was associated with a statistically significant reduction in risk of colorectal cancer (HR 0.76, 95% confidence interval [CI] 0.61-0.95, P=0.016). Meanwhile, in the analysis of non-time-to-event study results, statin use was associated with a trend towards lower colorectal cancer risk (OR 0.28, 95% CI 0.07-1.10, P=0.068). Conclusion Statin use appears to be associated with a reduced risk of colorectal cancer in patients with inflammatory bowel disease. Statins may serve as potential chemopreventive agents for long-standing IBD patients, and further large-scale prospective studies will be needed to confirm its potential benefit.

Association between serum γ-glutamyl transferase and advanced colorectal adenoma among inpatients: a case-control study.

Emerging evidence suggests a link between γ-glutamyl transferase (GGT) and various malignancies. However, the relationship between GGT and advanced colorectal adenoma, a critical precursor to colorectal cancer, remains unclear. This study aimed to elucidate this relationship. We conducted a single-center retrospective study from April 2015 to June 2022, enrolling 3534 inpatients including 525 cases and 3009 controls. Data were extracted from the electronic medical records, encompassing clinicodemographic characteristics, co-morbidities, and several blood biochemical indicators. Utilizing logistic regression and curve fitting, we explored the relationship between GGT and advanced colorectal adenoma. After adjustment for confounding factors, we found that for each 20-unit increase in GGT, the risk of advanced colorectal adenoma increased by 6% (OR= 1.06 [1.01-1.12]). Moreover, individuals with high GGT levels (≥50 U/L) had a 61% higher risk of advanced colorectal adenoma compared to those with low GGT levels (<50 U/L) (OR=1.61 [1.13-2.31]). Subgroup analysis demonstrated the robustness of these findings across subjects with different characteristics. High GGT levels were associated with higher odds of advanced colorectal adenoma. Our findings suggest that elevated GGT levels may serve as a potential diagnostic marker for advanced colorectal adenoma, providing new insights into its screening strategies.

Adenoma location, size, and morphology are risk factors for FOBT false-negative results in inpatients with advanced colorectal adenoma

Recently, advanced adenoma (AA) has been recognized as a target for colorectal cancer (CRC) screening. However, the fecal occult blood test (FOBT), the primary non-invasive screening method, shows limited sensitivity in detecting AA. This study investigates the relationship between adenoma characteristics and FOBT false-negative results. In a retrospective cohort study conducted from 2015 to 2022, we examined 342 inpatients with AA who underwent colonoscopy and received qualitative FOBT. FOBT sensitivity was analyzed about various adenoma characteristics, and logistic regression models were employed to investigate the relationship between adenoma features and FOBT false-negative outcomes. FOBT sensitivity in AA inpatients was 52.63%. Significant differences in sensitivity were observed based on adenoma location (left vs. right), morphology (with or without pedunculation), and size (≤ 10 mm vs. > 10 mm). After adjusting for several potential confounders, FOBT showed a reduced false-negative rate in AA with large-sized (OR, 0.49; 95% CI 0.31–0.77), left-sided location (OR, 0.53; 95% CI 0.31–0.89), and pedunculated morphology (OR, 0.73; 95% CI 0.43–1.24). AA with large size, left-sided location, and pedunculated morphology independently contribute to a decreased rate of FOBT false-negative results. However, these adenoma characteristics are not actively modifiable. Therefore, novel non-invasive methods are needed to improve AA detection accuracy.

Determination of dimethylated nucleosides in serum from colorectal cancer patients by hydrophilic interaction liquid chromatography-tandem mass spectrometry

RNA modifications play a crucial regulatory role in a variety of biological processes and are closely related to numerous diseases, including cancer. The diversity of metabolites in serum makes it a favored biofluid for biomarkers discovery. In this work, a robust and accurate hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS) approach was established for simultaneous determination of dimethylated nucleosides in human serum. Using the established method, we were able to accurately quantify the concentrations of N6-2′-O-dimethyladenosine (m6Am), N2,N2-dimethylguanosine (m2,2G), and 5,2′-O-dimethyluridine (m5Um) in serum samples from 53 healthy controls, 57 advanced colorectal adenoma patients, and 39 colorectal cancer (CRC) patients. The results showed that, compared with healthy controls and advanced colorectal adenoma patients, the concentrations of m6Am and m2,2G were increased in CRC patients, while the concentration of m5Um was decreased in CRC patients. These results indicate that these three dimethylated nucleosides could be potential biomarkers for early detection of colorectal cancer. Interestingly, the level of m5Um was gradually decreased from healthy controls to advanced colorectal adenoma patients to CRC patients, indicating m5Um could also be used to evaluate the level of malignancy of colorectal tumor. In addition, this study will contribute to the investigation on the regulatory mechanisms of RNA dimethylation in the onset and development of colorectal cancer.

PP031 Identification and evaluation of a serum microRNA panel for screening advanced colorectal adenomas

PP031 Identification and evaluation of a serum microRNA panel for screening advanced colorectal adenomas

Increased detection rates of advanced colorectal adenoma in women with metabolic dysfunction-associated fatty liver disease

BackgroundMetabolic dysfunction-associated fatty liver disease (MAFLD) is a new concept with its own diagnostic criteria. There are few studies on its relationship with colorectal adenoma. ObjectiveThis study aimed to explore the relationship between MAFLD and colorectal adenoma and to compare the predictive value of MAFLD with other risk factors. MethodsA total of 4436 consecutive physical examination subjects were enrolled. They all underwent colonoscopy and abdominal ultrasound. MAFLD was diagnosed by both fatty liver disease and metabolic dysfunction. The correlation between colorectal adenoma and MAFLD was studied using a logistic regression model. Results: The prevalence of MAFLD was 31.72 % (1407/4436). The adenoma detection rate in MAFLD patients was higher than that in controls (13.50 %, 190/1407 vs. 10.70 %, 324/3029, p < 0.001). Univariate analysis indicated that MAFLD individuals were 1.303-fold as likely to have colonic adenoma as controls [odds ratio (OR) 1.303 and 95 % confidence interval (CI), 1.076–1.578, p = 0.007]. Multivariate analysis showed that age, male sex, BMI and smoking were positively associated with the risk of colorectal adenoma, with OR values of 1.044 (95 % CI, 1.031 to 1.058), 1.720 (95 % CI, 1.221 to 2.424), 1.046 (95 % CI, 1.009 to 1.085) and 1.342 (95 % CI, 1.072 to 1.680), respectively. MAFLD in women, but not in men, had an independent relationship with increased detection of advanced adenoma (OR 3.932, 95 % CI, 1.023–15.1117, p = 0.046). ConclusionIndividuals with MAFLD are more likely to develop colorectal adenoma than those without MAFLD. The influence of MAFLD on advanced colorectal adenoma was especially prominent in females.

Does Chinese herbal medicine (CHM) reduce colorectal adenoma (CRA) recurrence: protocol of a registry-based, cohort study and a qualitative interview

IntroductionColorectal adenoma (CRA) is a precancerous lesion for colorectal cancer. Endoscopic resection is the first-line treatment for CRA. However, CRA recurrence rate is high. This proposed study aims to determine...

Efficacy and safety of combined EMR and endoscopic full-thickness resection (hybrid EFTR) for large nonlifting colorectal adenomas.

Endoscopic full-thickness resection (EFTR) with a full-thickness resection device (FTRD) has become the standard technique for selected nonlifting colorectal adenomas, but tumor size is the major limitation. However, large lesions might be approached in combination with EMR. Herein, we report the largest single-center experience to date of combined EMR and EFTR (hybrid EFTR) in patients with large (≥25mm) nonlifting colorectal adenomas not amenable to EMR or EFTR alone. This is a single-center retrospective analysis of consecutive patients who underwent hybrid EFTR of large (≥25mm) nonlifting colorectal adenomas. Outcomes of technical success (successful advancement of the FTRD with consecutive successful clip deployment and snare resection), macroscopic complete resection, adverse events, and endoscopic follow-up were evaluated. Seventy-five patients with nonlifting colorectal adenomas were included. Mean lesion size was 36.5mm (range, 25-60mm), and 66.6% were located in the right side of the colon. Technical success was 100% with macroscopic complete resection in 97.3%. Mean procedure time was 83.6 minutes. Adverse events occurred in 6.7%, leading to surgical therapy in 1.3%. Histology revealed T1 carcinoma in 16%. Endoscopic follow-up was available in 93.3% (mean follow-up time, 8.1 months; range, 3-36) and showed no signs of residual or recurrent adenoma in 88.6%. Recurrence (11.4%) was treated endoscopically. Hybrid EFTR is safe and effective for advanced colorectal adenoma that cannot be approached by EMR or EFTR alone. Hybrid EFTR expands the indication of EFTR substantially in selected patients.

Statin use and risk of colorectal cancer in patients with inflammatory bowel disease

Statin use has been linked to a reduced risk of advanced colorectal adenomas, but its association with colorectal cancer (CRC) in patients with inflammatory bowel disease (IBD) - a high risk population for CRC - remains inconclusive. From a nationwide IBD cohort in Sweden, we identified 5273 statin users and 5273 non-statin users (1:1 propensity score matching) from July 2006 to December 2018. Statin use was defined as the first filled prescription for ≥30 cumulative defined daily doses and followed until December 2019. Primary outcome was incident CRC. Secondary outcomes were CRC-related mortality and all-cause mortality. Cox regression estimated adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). During a median follow-up of 5.6 years, 70 statin users (incidence rate (IR): 21.2 per 10,000 person-years) versus 90 non-statin users (IR: 29.2) were diagnosed with incident CRC (rate difference (RD),-8.0 (95% CIs:-15.8 to-0.2 per 10,000 person-years); aHR=0.76 (95% CIs: 0.61 to 0.96)). The benefit for incident CRC was duration-dependent in a nested case-control design: as compared to short-term use (30 days to <1 year), the adjusted odd ratios were 0.59 (0.25 to 1.43) for 1 to <2 years of use, 0.46 (0.21 to 0.98) for 2 to <5 years of use, and 0.38 (0.16 to 0.86) for ≥5 years of use (Pfor tread=0.016). Compared with non-statin users, statin users also had a decreased risk for CRC-related mortality (IR: 6.0 vs. 11.9; RD,-5.9 (-10.5 to-1.2); aHR, 0.56 (0.37 to 0.83)) and all-cause mortality (IR: 156.4 vs. 231.4; RD,-75.0 (-96.6 to-53.4); aHR, 0.63 (0.57 to 0.69)). Statin use was associated with a lower risk of incident CRC, CRC-related mortality, and all-cause mortality. The benefit for incident CRC was duration-dependent, with a significantly lower risk after ≥2 years of statin use. This research was supported by Forte (i.e., the Swedish Research Council for Health, Working Life and Welfare).

Expression of Cyclooxygenase-2 in Patients With Snow-White Sign of Advanced Colorectal Adenomas

Objective To analyze the expression of cyclooxygenase-2 (COX-2) in the patients with snow-white sign of advanced colorectal adenoma (ACA) and explore its clinical significance.Method Western blotting was employed to determine the expression of COX-2 in the adenoma tissue and the normal tissue adjacent to the adenoma tissue (>5 cm away from the distal end of the adenoma tissue) of 40 ACA patients with snow-white sign and 40 ACA patients without snow-white sign.Results The appearance of snow-white sign in ACA patients was associated with patient age (P=0.001) and not associated with sex,smoking history,drinking history,ethnic groups,family history of colorectal cancer,abdominal pain,diarrhea,constipation,fecal occult blood,or tumor markers (all P>0.05).Snow-white sign mainly appeared in the ACA patients with multiple adenomas (P=0.004),large adenomas (P=0.006),adenomas in distal colon (P=0.015),protruding polyps (P=0.044),and late-stage pathology (P=0.010).The occurrence of snow-white sign showed no difference in the ACA patients with different results of Japan NBI Expert Team classification (P=0.502).The expression of COX-2 in the adenoma tissue was higher than that in the adjacent normal tissue in the patients with and without snow-white sign (P<0.001,P=0.004).The patients with snow-white sign had higher expression of COX-2 protein in the adenoma tissue than the patients without snow-white sign (P=0.001).The expression of COX-2 protein in the adjacent healthy tissue had no significant difference between the patients with and without snow-white sign (P=0.603).Conclusions Snow-white sign is more like to appear in the ACA patients with young age,multiple and large adenomas,adenomas in distal colon,protruding polyps,and late-stage pathology.Moreover,the expression of COX-2 in the ACA patients with snow-white sign is significantly higher than that in the ACA patients without snow-white sign.The adults with snow-white sign are prone to cancerization than those without snow-white sign.

UHPLC-HRMS-based serum untargeted lipidomics: Phosphatidylcholines and sphingomyelins are the main disturbed lipid markers to distinguish colorectal advanced adenoma from cancer

Colorectal advanced adenoma (CAA) is a key precancerous lesion of colorectal cancer (CRC), and early diagnosis can lessen CRC morbidity and mortality. Although abnormal lipid metabolism is associated with the development of CRC, there are no studies on the biomarkers and mechanism of lipid metabolism linked to CAA carcinogenesis. Hence, we performed a lipidomics study of serum samples from 46 CAA, and 50 CRC patients by the ultra high-performance liquid chromatography tandem high resolution mass spectrometry (UHPLC-HRMS) in both electrospray ionization (ESI) modes. Differential lipids were selected by univariate and multivariate statistics analysis, and their diagnostic performance was evaluated using a receiver operating characteristic curve (ROC) analysis. Combining P < 0.05 and variable importance in projection (VIP) > 1, 59 differential lipids were obtained totally. Ten of them showed good discriminant ability for CAA and CRC (AUC > 0.900). Especially, the lipid panel consisting of PC 44:5, PC 35:6e, and SM d40:3 showed the highest selection frequency and outperformed (AUC = 0.952). Additionally, phosphatidylcholine (PC) and sphingomyelin (SM) were the main differential and high-performance lipids. In short, this is the first study to explore the biomarkers and mechanism for CAA-CRC sequence with large-scale serum lipidomics. The findings should provide valuable reference and new clues for the development of diagnostic and therapeutic strategies of CRC.

Associations between Ileal Juice Bile Acids and Colorectal Advanced Adenoma.

There is an urgent need to identify biomarkers for advanced adenoma, an important precursor of colorectal cancer (CRC). We aimed to determine alterations in ileal juice bile acids associated with colorectal advanced adenoma. We quantified a comprehensive panel of primary and secondary bile acids and their conjugates using an ultraperformance liquid chromatography triple-quadrupole mass spectrometric assay in ileal juice collected at colonoscopy from 46 study subjects (i.e., 14 biopsy-confirmed advanced adenomas and 32 controls free of adenoma or cancer). Using analysis of covariance (ANCOVA), we examined the differences in bile acid concentrations by disease status, adjusting for age, sex, body mass index, smoking status and type 2 diabetes. The concentrations of hyodeoxycholic acid (HCA) species in ileal juice of the advanced adenoma patients (geometric mean = 4501.9 nM) were significantly higher than those of controls (geometric mean = 1292.3 nM, p = 0.001). The relative abundance of ursodeoxycholic acid (UDCA) in total bile acids was significantly reduced in cases than controls (0.73% in cases vs. 1.33% in controls; p = 0.046). No significant difference between cases and controls was observed for concentrations of total or specific primary bile acids (i.e., cholic acid (CA), chenodeoxycholic acid (CDCA) and their glycine- and taurine-conjugates) and total and specific major secondary bile acids (i.e., deoxycholic acid and lithocholic acid). Colorectal advanced adenoma was associated with altered bile acids in ileal juice. The HCA species may promote the development of colorectal advanced adenoma, whereas gut microbiota responsible for the conversion of CDCA to UDCA may protect against it. Our findings have important implications for the use of bile acids as biomarkers in early detection of colorectal cancer.

Association between Sleep Duration and Colorectal Adenomas: Findings from a Case-Control Study in Vietnam.

Colorectal cancer is one of the leading cancers worldwide and in Vietnam. Adenomas are important precursors of colorectal cancer. Study on the association between sleep duration and development of colorectal adenoma (CRA) is limited, particularly among Vietnamese population. We conducted an individually matched case-control study of 870 CRA cases and 870 controls in a large-scale colorectal screening program involving 103,542 individuals ages ≥40 years old in Hanoi, Vietnam. Sleep duration was categorized in three groups: short: ≤6 hours/day, normal: 7 to 8 hours/day, and long: >8 hours/day. Conditional logistic regression was used to evaluate the association between sleep duration and adenomas risk after controlling for potential confounders. Overall, short-sleep duration was associated with increased risk of having CRA compared with normal duration [OR, 1.48; 95% confidence interval (CI), 1.12-1.97]. This pattern was present in both females (OR, 1.58; 95% CI, 1.14-2.18) and males (OR, 1.45; 95% CI, 1.08-1.93), with advanced adenomas (OR, 1.61; 95% CI, 1.09-2.38) and non-advanced adenomas (OR, 1.66; 95% CI, 1.19-2.32). Furthermore, the association between CRA development and short-sleep duration was more apparent among females who were nondrinker, nonobese, physically active, with proximal or both sided adenomas and with cardiometabolic disorder. Among males, the short-sleep duration was associated with CRA risk among never-smoking, cardiometabolic disorders, and obese. Short-sleep duration was associated with increased prevalence of both advanced and non-advanced CRAs among Vietnamese population. Findings from this study showed that maintaining an adequate sleep duration may have an important implication for colorectal adenoma prevention and control.