Introduction

Colorectal cancer (CRC) is currently on of the most common cancer types worldwide and is the second leading cause of cancer-related mortality (Bray et al., 2018). Regardless of increasing access to CRC screening programs in many EU countries, more precise methods for early non-invasive disease discovery are highly needed (Kalager et al., 200; Benard et al., 2018). Currently CRC screening programs are based on fecal occult blood tests and/or colonoscopy, but this approach lacks of specificity and a large number or premalignant and malignant alterations in the colon are being overlooked (Click et al., 2019). Furthermore, current CRC programs result in high rate of expensive and unnecessary colonoscopy procedures, that pose significant risk for absolute healthy individuals (Ladabaum et al., 2019).
It is known that microbiome takes part in cancer genesis, its development, progression and even to its response to different treatment methods. Recent publication proves that gut microbiota (GM) can be used as novel biomarker tool in some disease (Russo et al., 2022, Roda et al., 2020). However, in order to, know whether microbiota is altered, studies identifying its profile in CRC patients are highly needed.

Aims & Methods

The aim of this study was to identify microbiome profile of CRC patients using gut mucosa biopsy and blood plasma samples.
In total, 313 individuals were included in this study, 104 of them were patients with CRC, 101 patients with adenomatous polyps (AP), and 108 were control individuals. Biopsies were taken from damaged mucosa during colonoscopy. Extracted DNA from all the samples was used to V1–V2 region of bacterial 16S rRNA gene amplification and sequencing on an Illumina MiSeq platform. To construct sample-similarity matrices abundances of taxonomic ranks in each sample type were used by applying Bray-Curtis algorithm. For significant differences between groups Permutational multivariate analysis of variance (PERMANOVA) and Mann-Whitney test followed by false-discovery rate test were used.

Results

Comparison between the global tissues bacterial assemblages revealed that the global structures at all taxonomic ranks were significantly different between control, CRC, and AP groups. Analysis revealed list of bacteria at the different taxonomic levels, the number of which was statistically significantly different between the groups. Moreover, analysis revealed bacteria that were associated with such clinical data as TNM classification, stage, and grade.

Conclusion

The global circulating and tissues microbiome profile of CRC and AP patients differs from that of the control group. Based on tissue and blood microbial profile it is possible to distinguish healthy state from CRC or AP. Mucosa tissue microbiome turns to be 20 times richer than blood microbiome. In CRC case bacterial richness and diversity decreases. Also there is distinct list of bacteria differed between CRC and control groups that could presumably be used as clinical biomarkers for CRC.

References

Bénard F, Barkun AN. Systematic review of colorectal cancer screening guidelines for average-risk adults: Summarizing the current global recommendations. World journal of gastroenterology. 2018; 24(1): 124. doi:
10.3748/wjg.v24.i1.124.
Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424. doi: 10.3322/caac.21492
Click B, Pinsky PF, Hickey T, et al. Association of Colonoscopy Adenoma Findings With Long-term Colorectal Cancer Incidence. JAMA, 2018; 319(19): 2021-31. doi: 10.1001/jama.2018.5809
Kalager M, Bretthauer M, et al. Improving cancer screening programs. Science. 2020; 367 (6474): 143-144; doi: 10.1126/science.aay3156
Ladabaum U, Mannalithara A, et al. Cost-Effectiveness and National Effects of Initiating Colorectal Cancer Screening for Average-Risk Persons at Age 45 Years Instead of 50 Years. Gastroenterology. 2019; 157(1):137-148. doi:
10.1053/j.gastro.2019.03.023
Senore C, Basu P, Anttila A, et al. Performance of Colorectal Cancer Screening in the European Union Member States: Data From the Second European Screening Report. Gut, 2019; 68(7):1232-44. doi: 10.1136/gutjnl-2018-317293
Roda G, Chien Ng S, et al. Crohn's disease. Nat Rev Dis Primers. 2020 Apr 2;6(1):22. doi: 10.1038/s41572-020-0156-2.
Russo E. The gut microbiota as a biomarker in epilepsy. Neurobiol Dis. 2022 Feb;163:105598. doi: 10.1016/j.nbd.2021.105598

Disclosure

The authors declare no conflict of interest.

Introduction

Physician adenoma detection rate (ADR) is associated with colorectal cancer risk after screening colonoscopy (post-colonoscopy CRC). Quality assurance e.g., using computer-aided detection, are increasingly used to improve ADR. It is unknown if increasing ADR for physicians with already adequate performance is beneficial for CRC prevention.

Aims & Methods

To determine whether increasing ADR for physicians with already adequate performance reduces the risk of CRC incidence and mortality after screening colonoscopy. We analyzed 485,615 screening colonoscopies performed by 789 physicians in the Polish CRC screening program between 2000 and 2017 and used joinpoint regression analyses to identify trends between ADR levels and post-colonoscopy CRC incidence and mortality with follow-up until December 2022. We also compared CRC risk forindividuals examined by physicians who did or did not improve performance by ADR levels

Results

During median follow-up of 10.2 years, we observed 1,873 CRCs and 474 CRC-related deaths. Median ADR was 21.8% (IQR15.9-28.2%), maximum ADR was 63.0%. Joinpoint regression analyses showed strongest associations between ADR and CRC incidence for physicians with ADR’s ≤26%, and weaker associations for physicians with ADR’s >26%. Increasing ADR from the lowest level to a 26% threshold reduced post-colonoscopy CRC incidence by 42.7per 100,000 person-years compared to 10.0 per 100,000 person-years for ADR increases from 26% to the maximum.For physicians with ADR of below 26% who increased ADR, post-colonoscopy CRC incidence was 31.8 (95%CI 29.5 to 34.3) per 100,000 person-years as compared to 40.7 (95%CI 37.8 to 43.8) for those who did not improve (Difference 8.9 per 100,000). For physicians with ADR of above 26% who increased ADR, post-colonoscopy CRC incidence was 23.4 (95%CI 18.4 to 29.8) per 100,000 person-years as compared to 22.5 (95%CI 18.3 to 27.6) for those who did not improve (Difference 0.9 per 100,000). CRC mortality yielded similar results .

Conclusion

Higher ADRs are significantly associated with lower CRC risk, but associations are weak and may not be clinically relevant for patients examined by physicians with already adequate detection rates

Disclosure

​None

Introduction

Ongoing screening programs should be monitored and evaluated regularly to ensure a favorable balance between their harms and benefits. In 2022, the Dutch Health Council performed an evaluation commissioned by the Minister of Health of the first seven years of the population-based colorectal cancer (CRC) screening program in the Netherlands.

Aims & Methods

This study describes the key performance indicators used for this large evaluation in 2022. Population-based CRC screening in the Netherlands was initiated in 2014 with a phased roll-out by birth cohort, inviting individuals aged 55 to 75 to perform a faecal immunochemical test (FIT) using a positivity cut-off of 47 µg Hb/g faeces every two years. We calculated key performance indicators based on individual-level data from participants between 2014 and 2020 (up to four screening rounds) and presented outcomes by sex, round and prior faecal haemoglobin concentration (fHb). Also, we calculated the overall and advanced (stage III and IV) CRC incidence rate in 2013, 2015 and 2018 for advanced CRC incidence rate and 2019 for overall CRC incidence rate. Last, FIT episode sensitivity was calculated for three screening rounds between 2014 and 2018.

Results

FIT participation was high, especially among women, but slightly decreased over time. (Table 1) Colonoscopy participation remained stable (~85%). FIT positivity rate decreased from 5.6% to 4.3% after the first round and was higher for men than women. Similar patterns were observed for PPV and detection rates. The false-positivity rate was stable over three screening rounds (2.7 for men and 2.1 for women). The colonoscopy complication rate was less than 1%. For individuals with prior fHb just below the cut-off (15.0-46.9 µg Hb/g), FIT positivity and detection rates were significantly higher than for individuals with lower fHb. After the introduction of the screening program, the age-standardized overall CRC incidence rate initially increased from 214.3 in 2013 to 259.2 in 2015 but subsequently decreased below the level before screening to 181.5 in 2019. The same pattern was also visible for the advanced CRC incidence rate which increased from 117.0 in 2013 to 122.8 in 2015 and decreased to 94.7 in 2018.

Table 1 Key performance indicators in the evaluation by the Health Council of the population-based CRC screening program in the Netherlands.

Conclusion

Based on these key performance indicators, the Health Council concluded that the Dutch CRC screening program has a favorable harm-benefit ratio. The Council recommended future research into increasing participation in underserved populations or improving the program with a personalized invitation or screening strategy.

Introduction

The current screening and diagnostic methods for colorectal cancer (CRC) primarily involve tumor markers, imaging examinations, and endoscopic evaluations, which have inherent limitations. Therefore, it is imperative to explore novel diagnostic techniques for early-stage CRC to improve patient prognosis and survival rates. Recent studies have demonstrated the significant potential of circulating exosome-associated microRNAs (miRNAs) as biomarkers in CRC; however, these investigations are limited and predominantly focused on advanced tumors. Consequently, the differences in circulating exosomal miRNAs, among different stages of CRC within the classic developmental model of 'normal mucosa, adenoma, early adenocarcinoma, advanced adenocarcinoma', remain unknown.

Aims & Methods

Plasma exosomes were isolated from colorectal adenoma (CRA), early CRC (Tis-T1), advanced CRC (T2-T4), and healthy control (NC) groups (n=5 for each group) using ultracentrifugation. The miRNA expression profiles of plasma exosomes in the four groups were compared using miRNA microarray analysis to identify differentially expressed miRNAs in the three colorectal disease groups compared to the NC group. The results of miRNA microarray detection were validated by qRT-PCR to increase the sample size (n=30 for each group) and confirm the expression of characteristic miRNAs identified. Receiver operating characteristic curves were utilized to assess the diagnostic efficacy through area under curve (AUC).

Results

The extracted exosomes exhibited consistent morphology, size, and expression of protein markers that align with the fundamental characteristics of exosomes. Microarray analysis results revealed that both early and advanced CRC groups shared 31 up-regulated miRNAs and 34 down-regulated miRNAs compared to the CRA and NC groups. By intersecting with the GSE40247 dataset (CRC cell secreted exosome-derived microarray results), we identified five up-regulated miRNAs (miR-150-3p, miR-1224-5p, miR-1246, miR-1268a, and miR-1290). The expression levels of all five miRNAs showed a progressive increase with CRC advancement at different developmental stages. Notably, significant diagnostic potential was observed for miR-1224-5p, miR-1246, and miR 1290 in distinguishing patients with early CRC from NC (AUC 0.638 to 0.719). All five identified miRNAs demonstrated relatively good diagnostic performance in discriminating patients with advanced CRC from NC (AUC 0.745 to 0.838), while none of them had clear diagnostic value in distinguishing early CRC patients from individuals with CRA (AUC 0.548 to 0.654). Logistic regression analysis was employed to construct a multi-panel diagnosis model based on three specific miRNAs: miR-1224 -5p ,miR-1246, and miR-1290. The combined AUCs were found to be as follows: for discrimination between early CRC and NC groups, AUC=0.817 (P=0.0008); for discrimination between advanced CRC and NC groups, AUC=0.907 (P<0.0001); for discrimination between early CRC and CRA groups, AUC=0.754 (P=0.0035).

Conclusion

The miRNA expression profiles of plasma exosomes in early CRC patients exhibit similarities to those observed in advanced CRC patients. Specifically, the presence of miR-150-3p, miR-1224-5p, miR-1246, miR-1268a, and miR-1290 within plasma exosomes can serve as reliable indicators for the diagnosis of CRC. Importantly, a combination of miR-1224-5p, miR-1246, and miR-1290 shows promise for the early detection of CRC.