Metabolic dysregulation has been implicated as a key factor in colorectal cancer (CRC) initiation, however, the underlying driving forces and mechanisms remain poorly understood. Herein, transcriptome profiling of paired early-stage CRCs and adenomas identifies Nudix hydrolase 13 (NUDT13) as a critical suppressor. Elevated NUDT13 expression impedes the proliferation of CRC cells under hypoxic conditions and markedly inhibits CRC initiation by upregulating PKM1. Mechanistically, NUDT13 directly binds and stabilizes PKM1 protein by reducing its poly ADP-ribosylation (PARylation), which is catalyzed by PARP1 at E275/D281/E282/E285/D296, thereby inducing an oxidative phosphorylation (OXPHOS) phenotype in CRC cells. Moreover, spatiotemporal knockout of Nudt13 enhances intestinal tumorigenesis in mice, which can be significantly suppressed by PARP1 inhibitor Olaparib. Notably, residues E245/E248/E249 within the Nudix box motif of NUDT13 are essential for PKM1 PARylation, and a mimic peptide derived from this motif is sufficient to stabilize PKM1 protein and robustly inhibit CRC tumorigenesis. Collectively, this study reveals a previously unknown PARylation-dependent mechanism that regulates PKM1 protein stability and switches the metabolic pathway of CRC cells, providing a promising target for CRC treatment.

This American Gastroenterological Association (AGA) guideline is intended to provide an overview of the evidence and support endoscopists and patients on the use of computer-aided detection (CADe) systems for the detection of colorectal polyps during colonoscopy.

A multidisciplinary panel of content experts and guideline methodologists used the Grading of Recommendations Assessment, Development and Evaluation framework and relied on the following sources of evidence: (1) a systematic review examining the desirable and undesirable effects (ie, benefits and harms) of CADe-assisted colonoscopy, (2) a microsimulation study estimating the effects of CADe on longer-term patient-important outcomes, (3) a systematic search of evidence evaluating the values and preferences of patients undergoing colonoscopy, and (4) a systematic review of studies evaluating health care providers' trust in artificial intelligence technology in gastroenterology.

The panel reached the conclusion that no recommendation could be made for or against the use of CADe-assisted colonoscopy in light of very low certainty of evidence for the critical outcomes, desirable and undesirable (11 fewer colorectal cancers per 10,000 individuals and 2 fewer colorectal cancer deaths per 10,000 individuals), increased burden of more intensive surveillance colonoscopies (635 more per 10,000 individuals), and cost and resource implications. The panel acknowledged the 8% (95% CI, 6%-10%) increase in adenoma detection rate and 2% (95% CI, 0%-4%) increase in advanced adenoma and/or sessile serrated lesion detection rate.

This guideline highlights the close tradeoff between desirable and undesirable effects and the limitations in the current evidence to support a recommendation. The panel acknowledged the potential for CADe to continually improve as an iterative artificial intelligence application. Ongoing publications providing evidence for critical outcomes will help inform a future recommendation.

Colorectal cancer (CRC) incidence is associated with lower circulating selenium and zinc and elevated copper concentrations. Moreover, copper and selenium accumulate within tumor tissue, indicating a disturbed homeostasis of these essential trace elements in CRC.

This study aimed to identify associations between CRC characteristics (based on genomic, transcriptomic and proteomic data) and trace element concentrations.

The concentrations of copper, selenium, and zinc were measured in 83 human CRC cell lines and correlated with transcript and protein expression levels to identify trace element-related gene signatures. By using publicly available gene expression data from The Cancer Genome Atlas we investigated the association between those signatures with the survival probability of CRC patients.

The CRC cell lines differed in their copper (fold change 7.3), selenium (fold change 6), and zinc (fold change 2.6) concentrations. The concentrations were not associated with genetic or cellular characteristics, except for lower copper concentrations in KRAS mutant cells. Expression levels of known copper- and zinc-related proteins correlated significantly with the respective trace element concentrations, serving as a proxy for trace element concentrations in tumors, and with patient survival. This was not the case for selenium and selenoproteins. In addition, an unbiased approach identified novel high and low copper- and zinc-related gene expression signatures significantly associated with patient's outcome.

Herein we identify gene signatures associated with intracellular copper and zinc concentrations in CRC cell lines. Extrapolating these signatures to primary colorectal tumors revealed that they can inform outcome of CRC patients.

Early detection is paramount when reducing incidence and mortality of colorectal cancer (CRC). Current population-based screening programs primarily use fecal immunochemical test (FIT) to allocate individuals for colonoscopy although low specificity challenges colonoscopy capacities. We aimed to assess the potential of circulating tumor (ct)DNA markers for early CRC detection in a dual-test CRC screening approach among FIT positive individuals.

Plasma samples from 774 FIT positive (≥100 ng Hemoglobin/mL) individuals from the Danish CRC screening program were analyzed for hypermethylated DNA in the genes Branched Chain Amino-acid Transaminase 1 (BCAT1), Ikaros-Family Zinc Finger transcription 1 (IKZF1), and Interferon Regulator Factor 4 (IRF4). Multivariate logistic regression models were generated adding the ctDNA markers and age to the FIT value. The dual-test approach was benchmarked to FIT at specific thresholds.

The dual-test approach improved CRC detection compared to the FIT alone (AUC of 87.2 [95% CI, 82.9-91.4] vs AUC of 72.5 [95% CI, 67.0-77.9]). This was also seen when adding advanced adenomas to the outcome resulting in AUCs of 71.8 [95% CI, 67.8-75.8] for the dual-test approach compared to 65.5 [95% CI, 61.3-69.7] for the FIT model alone. Benchmarking the dual-test approach at FIT cut-offs between 100 and 600 ng Hb/mL showed a potential for either reducing the colonoscopy requirement by up to 56% or increasing CRC detection by up to 28%.

As increasing FIT cutoff will decrease CRC detection rate, application of the ctDNA panel can increase the sensitivity and specificity in a dual-test approach among asymptomatic individuals.

Background/Objectives: Research on colorectal adenoma is significantly less comprehensive compared to studies on colorectal carcinoma. Although colorectal adenoma is a precursor of the majority of sporadic colorectal cancers, not all adenomas develop into carcinomas. The complex interaction of immune responses in the premalignant tumor microenvironment might be a factor for that. Methods: In this systematic review, we aim to provide a thorough analysis of the current research examining the immune infiltration patterns in sporadic colorectal adenoma tissues in the context of immune cell-based, cytokine-based, and other immunological factor-related changes along the conventional adenoma-carcinoma sequence. The articles included in the review extend up to December 2024 in PubMed and Web of Science databases. Results: Most included studies have shown significant differences in immune cell counts, densities, and cytokine expression levels associated with premalignant colorectal lesions (and/or colorectal cancer). No consensus on the immune-related tendencies concerning CD4+T cells and CD8+T cells was reached. Decreasing expression of mDCs and plasma and naïve B cells were detected along the ACS. The increased density of tissue eosinophils in the adenoma tissue dramatically diminishes after the transition to carcinoma. As the adenoma progresses, the increasing expression of IL-1α, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-21, IL-23, IL-33, and TGF-β and decreasing levels of IL-12A, IL-18, IFN-γ, and TNFα cytokines in the invasive carcinoma stage is being detected. The over-expression of COX-2, PD-1/PD-L1, CTLA-4, and ICOS/ICOSLG in the colorectal adenomatous and cancerous tissues was also observed. Conclusions: Further studies are needed for a better understanding of the whole picture of colorectal adenoma-associated immunity and its impact on precancerous lesion's potential to progress.

This study reports the design, synthesis, and characterization of a novel series of benzene sulfonamide-triazole hybrid derivatives, to evaluate their anticancer potential against colorectal cancer. The synthesized compounds were characterized using NMR and HRMS spectroscopic techniques. In vitro cytotoxicity assessments revealed that compounds 5g and 5j exhibited significant anticancer effects. 5g showed the highest potency in the DLD-1 cell line (IC50 = 11.84 µM), while 5j demonstrated robust activity in the HT-29 cell line (IC50 = 9.35 µM). Apoptotic analysis indicated that compound 5g effectively induced early and total apoptosis, surpassing the chemotherapeutic agent 5-fluorouracil (5-FU), highlighting its therapeutic potential. Molecular docking studies showed strong binding interactions with key proteins involved in colorectal cancer progression, such as TGFβ2 and VEGFR1. 5j displayed a high binding affinity for TGFβ2 (MM-GBSA ΔG = -92.52 kcal/mol) and 5g showed promising interactions with VEGFR1 (ΔG = -70.63 kcal/mol). Molecular dynamics simulations confirmed the stability of the ligand-protein complexes, indicating potential as targeted therapeutic agents. Compounds 5g and 5j demonstrate significant promise for further development in colorectal cancer treatment.

Microsatellite instability (MSI) stratification can guide the clinical management of patients with colorectal cancer (CRC). This study aimed to establish a radiomics model for predicting the MSI status of patients with CRC before treatment.

This retrospective study was performed on 366 patients diagnosed with CRC who underwent preoperative magnetic resonance imaging (MRI) and immunohistochemical staining between February 2016 and September 2023. The participants were divided randomly into training and testing cohorts in a 7:3 ratio. The tumor volume of interest (VOI) was manually delineated on T2-weighted imaging (T2WI) and apparent diffusion coefficient (ADC) sequences using 3D Slicer software, and radiomics features were extracted. Feature selection was performed using the least absolute shrinkage and selection operator method. A radiomics nomogram was developed using multiple logistic regression, and the predictive performance of the models was evaluated and compared using receiver operating characteristic curves. The calibration curve, clinical decision curve analysis (DCA) and clinical impact curve (CIC) were used to evaluate the clinical application value of the model.

The radiomics normogram combined with history of chronic enteritis, tumor location, MR-reported inflammatory response, D2-40, carcinoembryonic antigen, tumor protein 53, and monocyte was an excellent predictive tool. The area under the curve for the training and testing cohorts were 0.927 and 0.984, respectively. The DCA and CIC demonstrated favorable clinical application and net benefit.

A radiomics nomogram based on T2WI and ADC sequences and clinicopathologic features can effectively and noninvasively predict the MSI status in CRC. This approach helps clinicians in stratifying CRC patients and making clinical decisions for personalized treatment.

Chronic gut inflammation and dysbiosis contribute significantly to colorectal cancer (CRC) development. Shaoyao decoction (SYD) is a well-established Chinese medicine prescription. Besides ameliorating CRC via anti-inflammatory effects, SYD modulates gut microbiota (GM) to improve inflammatory responses in ulcerative colitis (UC). However, whether and how SYD suppresses CRC by regulating GM remains largely unknown.

SD rats were orally administered SYD for 7 days to obtain medicated serum. We utilized liquid chromatography-mass spectrometry (LC-MS) analysis, GeneCards, DisGeNET, and SwissTargetPrediction databases to analyze blank and SYD-medicated rat serum, comparing the findings with those of SYD aqueous extract in previous studies to identify SYD circulating compounds/components with predictable target genes. Using network pharmacology, the potential active compounds and corresponding hub genes associated with modulating GM to suppress CRC were selected for molecular docking. In vivo experiments, a CRC transplantation tumor model was established in BALB/c mice using CT26 cells, with SYD gavage for 14 days. To investigate the mechanism of SYD-regulated GM against CRC, HE and IHC staining, Western blotting, and 16S rRNA sequencing were employed.

LC-MS identified 26 SYD compounds with computationally predicted target genes. Network pharmacology prioritized 13 compounds targeting 8 inflammation/immunity-related genes (IL-17/TNF pathways), validated by molecular docking. In vivo experiments, SYD dose-dependently suppressed tumor growth (p < 0.05, medium/high doses), as confirmed by HE staining and IHC analysis of Ki-67. Notably, SYD potentially delayed CRC liver metastasis and alleviated hepatic injury in tumor-bearing mice. Western blotting demonstrated SYD's inhibition of the IL-17/TNF/NF-κB axis, aligning with computational predictions. 16S rRNA sequencing revealed SYD-enriched Akkermansia and GM structural shifts, mechanistically linking microbiota remodeling to anti-tumor efficacy.

SYD combats CRC via dual modulation of IL-17/TNF/NF-κB signaling and GM ecosystems (e.g., Akkermansia enrichment). This microbiota-immune crosstalk positions SYD as a potential adjunct to conventional therapies, particularly for CRC patients with dysbiosis.

The vast majority of colon cancers occur in pre-existing adenomas. Little is known about the impact of adenoma type on behavior and outcome of subsequent carcinomas. The present study aimed to assess characteristics, behavior, and outcome of colon adenocarcinoma based on histologic type of pre-existing adenoma.

US-National Cancer Database was searched between 2005 and 2019 for patients with colonic adenocarcinoma with known adenoma type who underwent colectomy. Patients were divided into 3 groups according to type of adenoma in which carcinoma developed: tubular adenoma (TA), villous adenoma (VA), and tubulovillous adenoma (TVA)-associated carcinomas. The main outcome of the study was 5-year overall survival (OS).

66,854 patients were included. 79.3% of carcinomas originated from TVA, 10.2% from VA, and 0.5% from TA. Patients with adenocarcinoma in VA were more often female whereas carcinomas in TA affected patients of Asian race more often. Approximately one-third of carcinomas in villous and tubulovillous adenomas were in the cecum whereas one-third of carcinomas in tubular adenomas were in the sigmoid colon. More TA-associated carcinomas were of clinical T1-2 stage (30.2% vs. 20.8%; P < .001), clinical N0 stage (69% vs. 62.2%, P < .001), and high grade (15.9% vs. 11.5%, P < .001) compared to VA-associated carcinomas. Patients with TA-associated carcinomas had longer mean OS than patients with VA and TVA-associated carcinomas (130.1 vs. 116.9 vs. 123.5 months, P < .0001).

Adenocarcinomas that arose in TA had more T1-2 stage and N0 stage, higher grade, and longer OS than did adenocarcinomas that arose in VA and TVA.

Novel thiazepine-based hybrids (9 a-d) were designed and synthesized to create lead molecules with exceptional anti-colon cancer efficacy. Analytical methods, including IR, NMR, and HR-MS, characterized the synthesized compounds. The in vitro colorectal study was carried out to compare the biological activity of newly developed compounds with the computational data. The tested compounds induced cytotoxicity in HT-29 cells for both 24 h and 48 h in a dose-dependent manner. However, compound 9 a induced cytotoxicity at much higher concentrations compared to the rest of the compounds. 9 b and 9 c caused 50 % cell death (compared to the untreated cells) at a dose of ~50 μM and 40 μM in case of 24-hour exposure, respectively. On the contrary, for 48 h exposure, both 9 b and 9 c induced 50 % cell death concerning untreated cells at a dose of around ~20 μM, whereas 9 d exhibited 50 % cell death at 5 μM in the case of 48 h exposure. In silico ADMET was also carried out to understand the pharmacokinetics and safety profiles of the drug candidates. We found some of the critical targets of these compounds, which eventually will be integral to exploring the mechanistic actions of these compounds in colon cancer.

Colorectal cancers (CRCs) are traditionally divided into those with either chromosomal instability (CIN) or microsatellite instability (MSI). By utilizing TCGA data, the Laird team found a subset of CRCs, namely, genome-stable CRCs (GS CRCs), which lack both CIN and MSI. Although the molecular features of GS CRCs have been described in detail, the clinicopathological features are not well defined. A total of 437 CRCs were analyzed for copy number variation (CNV) statuses in eight genes (ARID1A, EGFR, FGFR1, KDM5B, MYBL2, MYC, SALL4, and SETDB1) using droplet-digital PCR. CRCs that showed CNV in ≤ one gene and no MSI were defined as GS-like CRCs. Clinicopathological and molecular features of GS-like CRCs were compared with those of CIN-like CRCs. GS-like CRCs comprised 4.6% of CRCs and showed a predilection toward the proximal colon, lower nuclear optical density, KRAS mutation, PIK3CA mutation, and aberrant expression of KRT7. Survival analysis showed no significant difference between the three subgroups. Through our study, the GS-like subtype was found to comprise a minor proportion of CRCs and have proclivity toward a proximal bowel location, hypochromatic tumor nuclei, aberrant KRT7 expression, and a high frequency of KRAS and PIK3CA mutations.

This research aimed to investigate the effect of 6-Paradol on sorafenib cytotoxicity in colorectal cancer (CRC) cell lines (HT-29, HCT-116, LS-174T, CaCo-2) through its effects on cellular processes.

CRC, which ranks as the third most prevalent cancer, arises in the colon or rectum due to a multifaceted interplay of dietary, lifestyle, genetic, and age-related factors. Sorafenib (multikinase inhibitor), a drug targeting multiple cancer signals, shows promise against liver, thyroid, and kidney tumors but faces resistance in CRC. 6-Paradol (Zingiberaceae), a natural compound, offers the potential for overcoming this resistance.

The current study investigates whether 6-paradol potentiates sorafenib's anti-cancer activity in CRC cells by promoting increased drug entrapment, uptake, and metabolism.

Sulpharodamine B assay, caspase-3 activity, PARP cleavage, cell cycle distribution analysis, and P-gp efflux activity were assessed for Cytotoxicity using CRC cell lines (HT-29, HCT-116, LS-174T, CaCo-2).

Sorafenib showed potent cytotoxicity across CRC cell lines (IC50: 2.0-11.1 µM). Notably, 6-Paradol synergistically enhanced its effect in HT-29 and HCT-116 cells, reducing IC50 from 338 ± 55.7 to 107 ± 5.3 µM, respectively. 6-Paradol synergized with sorafenib, reducing HCT-116 cell proliferation from from 14.25 ± 0.62 to 20.7 ± 0 fg/cell and Paradol didn't show any significant change in c-PARP concentration which equaled 289.82 ± 27.32 pg/cell, suggesting enhanced cytotoxicity. 6-Paradol exposure resulted in a concentration-dependent (1-100 µM) increase in intracellular p-gp accumulation in CaCo-2, HCT-116, and HT-29. Co-incubation with 6-paradol significantly enhanced sorafenib cellular internalization within CaCo-2 cells, resulting in a concomitant decrease in its extracellular concentration from 1491 ± 132 ng/ml to 216 ± 39 ng/ml. 6-Paradol increased sorafenib intracellular accumulation ranges from 239 ± 16 to 327 ± 34 pg/cell, respectively in HCT-116 cells. 6-Paradol significantly increased the intracellular conversion of sorafenib to its active N-oxide metabolite and facilitated its retention within the CaCo-2 cell compartment.

In conclusion, 6-Paradol marked elevation in sorafenib's cytotoxic profile by influencing its cellular uptake and metabolism. Future research should expand in vitro studies to diverse cell lines, conducting in vivo elucidating underlying mechanisms and rigorously evaluating safety and toxicity.

Mutations in KRAS and BRAF genes are prevalent in colorectal cancer (CRC), which strikingly promote tumorigenesis and lead to poor response to a variety of treatments including immunotherapy by activating the MAPK/ERK pathway. Thus, there is an urgent need to discover effective therapeutic targets and strategies.

CRISPR-Cas9 lentiviral knockout library was used to screen the suppressors of anti-PD1 immunotherapy. Bioinformatic analysis was used to analyze the correlation between PHF8 expression and immune indicators in CRC. In vitro and in vivo experiments were utilized to determine the effects of PHF8 on the immune indexes and malignant phenotypes of CRC cells. qRT-PCR, western blotting, immunohistochemical (IHC) staining, and chromatin immunoprecipitation (ChIP)-qPCR assays were used to determine the regulatory effects of PHF8 on PD-L1, KRAS, BRAF, and c-Myc and the regulatory effect c-Myc/miR-22-3p signaling axis on PHF8 expression in CRC cells.

This study identified histone lysine demethylase PHF8 as a negative regulator for the efficacy of anti-PD1 therapy and found that it was highly expressed in CRCs and strongly associated with poor patient survival. Functional studies showed that PHF8 played an oncogenic role in KRAS- or BRAF-mutant CRC cells, but not in wild-type ones. Mechanistically, PHF8 up-regulated the expression of PD-L1, KRAS, BRAF, and c-Myc by increasing the levels of transcriptional activation marks H3K4me3 and H3K27ac and decreasing the levels of transcriptional repression mark H3K9me2 within their promoter regions, promoting immune escape and tumor progression. Besides, our data also demonstrated that PHF8 was up-regulated by the c-Myc/miR-22-3p signaling axis to form a positive feedback loop. Targeting PHF8 substantially improved the efficacy of anti-PD1 therapy and inhibited the malignant phenotypes of KRAS- or BRAF-mutant CRC cells.

Our data demonstrate that PHF8 may be an effective therapeutic target for KRAS- or BRAF-mutant CRCs.

Low relative muscle mass was identified to be related to ascending risk of pre-cancerous polyps (adenoma) in recent cohort study. Our study aimed to dig out the correlation between muscle mass and different pathological types of colorectal polyps in Chinese asymptomatic population.

In all, 5923 adults were included. The effects of low skeletal muscle mass index (SMI) on colorectal polyp occurrence, including different pathological types, and the effects modification of age and BMI were analyzed using univariate and multivariate logistic regression.

Lower SMI was connected with the lower occurrence of colorectal polyp (OR: 0.810, 95% CI: 0.683~0.960, p=0.015). Considering different pathological types of colorectal polyps, lower SMI was associated with lower occurrence of inflammatory polyp (OR: 0.633, 95% CI: 0.434~0.898, p=0.013), rather than conventional adenoma and serrated polyp (all p>0.05). Besides, SMI was positively related to the occurrence of 2 pathological types of colorectal polyp in males: inflammatory polyp (OR: 1.237, 95% CI: 1.058~1.444, p=0.007) and serrated polyp (OR: 1.288, 95% CI: 1.143~1.456, p<0.001). The interaction effect of BMI and SMI on occurrence of inflammatory polyp after adjusting age and smoking status was significant (p=0.015). For individuals with low SMI (compared with the normal SMI group), the incidence of inflammatory polyp was reduced from 8.95% to 3.50% in the low BMI quartile (Q1) in the adjusted model (OR of 0.332, 95% CI: 0.005-0.061, p<0.001). It was noticeable for males rather than females that individuals with colorectal polyps had higher levels of SMI (p=0.003). In addition, individuals with inflammatory polyps as well as serrated polyps possessed higher levels of SMI in males (all p<0.05).

Generally, especially in Chinese asymptomatic males, low SMI kept independent effect on the presence of inflammatory polyp and serrated polyp, rather than conventional adenoma.

Early detection of colorectal cancer (CRC) significantly improves its management and patients' survival. Circular RNAs (circRNAs) are peculiar covalently closed transcripts involved in gene expression modulation whose dysregulation has been extensively reported in CRC cells. However, little is known about their alterations in the early phases of colorectal carcinogenesis.

In this study, we performed an integrative analysis of circRNA profiles in RNA-sequencing (RNA-Seq) data of 96 colorectal cancers, 27 adenomas, and matched adjacent mucosa tissues. We also investigated the levels of cognate linear transcripts and those of regulating RNA-binding proteins (RBPs). Levels of circRNA-interacting microRNAs (miRNAs) were explored by integrating data of small RNA-Seq performed on the same samples.

Our results revealed a significant dysregulation of 34 circRNAs (paired adj. p < 0.05), almost exclusively downregulated in tumor tissues and, prevalently, in early disease stages. This downregulation was associated with decreased expression of circRNA host genes and those encoding for RBPs involved in circRNA biogenesis, including NOVA1, RBMS3, and MBNL1. Guilt-by-association analysis showed that dysregulated circRNAs correlated with increased predicted activity of cell proliferation, DNA repair, and c-Myc signaling pathways. Functional analysis showed interactions among dysregulated circRNAs, RBPs, and miRNAs, which were supported by significant correlations among their expression levels. Findings were validated in independent cohorts and public datasets, and the downregulation of circLPAR1(2,3) and circLINC00632(5) was validated by ddPCR.

These results support that multiple altered regulatory mechanisms may contribute to the reduction of circRNA levels that characterize early colorectal carcinogenesis.

Comprehensive protein profiling in intestinal tissues provides detailed information about the pathogenesis of colorectal cancer (CRC). This study quantified the expression levels of 92 oncology-related proteins in tumors, paired para-carcinoma tissues, and remote normal tissues from a cohort of 52 CRC patients utilizing the Olink technology. The proteomic profile of normal tissues closely resembled that of para-carcinoma tissues while distinctly differing from that of tumors. Among the 68 differentially expressed proteins (DEPs) identified between the tumor and normal tissues, WISP-1, ESM-1, and TFPI-2 showed the most pronounced alterations and exhibited relatively strong correlations. These markers also presented the highest AUC values for distinguishing between tissue types. Bioinformatic analysis of the DEPs revealed that the plasma membrane and the PI3K-AKT signaling pathway were among the most enriched GO terms and KEGG pathways. Furthermore, although TFPI-2 is typically recognized as a tumor suppressor, both Olink and enzyme linked immunosorbent assay (ELISA) analyses have demonstrated that its expression is significantly elevated in tumors compared with paired normal tissues. To the best of our knowledge, this is the first study to profile the proteome of intestinal tissue using the Olink technology. This work offers valuable insights into potential biomarkers and therapeutic targets for CRC, complementing the Olink profiling of circulating proteins.

Colorectal cancer (CRC) is an exceedingly common and profoundly impactful malignancy of the digestive system, posing a grave threat to human health. Endoplasmic reticulum stress (ERS) is an intracellular biological reaction that mobilizes the unfolded protein response (UPR) to tackling dysregulation in protein homeostasis. This process subtly modulates the cell to either restore normal cellular function or steer it towards apoptosis. The high metabolic demands of CRC cells sculpt a rigorous tumor microenvironment (TME), compelling CRC cells to experience ERS. Adaptive responses induced by mild ERS furnish the necessary conditions for the survival of CRC cells, whereas the cell death mechanisms triggered by sustained ERS could be considered a prospective strategy for cancer therapy. Considering the complex regulation of ERS in cancer development, this article offers a comprehensive review of the molecular mechanisms through which ERS influences CRC fate. It provides crucial insights for exploring the role of ERS in the occurrence and progression of CRC, laying a new theoretical foundation for devising precise therapeutic strategies targeting ERS. Furthermore, by synthesizing extensive clinical and preclinical studies, we delve into therapeutic strategies targeting ERS, including the potential of targeting ERS in immunotherapy, the utilization of native compounds, advancements in proteasome inhibitors, and the potential synergies of these strategies with traditional chemotherapy agents and emerging therapeutic approaches.

Colorectal cancer (CRC) arises from the epithelial lining of the colon or rectum, often following a progression from benign adenomatous polyps to malignant carcinoma. Screening modalities such as colonoscopy, faecal immunochemical tests (FIT), and FIT-DNA are critical for early detection and prevention, but non-invasive methods lack sensitivity to polyps and early CRC. Chromosome conformations (CCs) are potent epigenetic regulators of gene expression. We have previously developed an epigenetic assay, EpiSwitch®®, that employs an algorithmic-based CCs analysis. Using EpiSwitch®® technology, we have shown the presence of cancer-specific CCs in peripheral blood mononuclear cells (PBMCs) and primary tumours of patients with melanoma and prostate cancer. EpiSwitch®®-based commercial tests are now available to diagnose prostate cancer with 94% accuracy (PSE test) and response to immune checkpoint inhibitors across 14 cancers with 85% accuracy (CiRT test). Methods/Results/Conclusions: Using blood samples collected from n = 171 patients with CRC, n = 44 patients with colorectal polyps and n = 110 patients with a 'clear' colonoscopy we performed whole Genome DNA screening for CCs correlating to CRC diagnosis. Our findings suggest the presence of two eight-marker CC signatures (EpiSwitch®® NST) in whole blood that allow diagnosis of CRC and precancerous polyps, respectively. Independent validation cohort testing demonstrated high accuracy in identifying colorectal polyps and early versus late stages of CRC with an exceptionally high sensitivity of 79-90% and a high positive prediction value of 60-84%. Linking the top diagnostic CCs to nearby genes, we have built pathways maps that likely underline processes contributing to the pathology of polyp and CRC progression, including TGFβ, cMYC, Rho GTPase, ROS, TNFa/NFκB, and APC.

Colorectal cancer (CRC) ranks as the third most commonly diagnosed cancer and the second leading cause of cancer-related deaths worldwide. Studies have shown that CRC patients with KRAS mutations, especially KRASG12D, have an increased risk of metastasis. Emerging evidence indicates that long non-coding RNAs (lncRNAs) are crucial in the carcinogenesis and progression of various cancers, regulating multiple biological processes but the link between KRASG12D mutations and lncRNAs in CRC remains unclear. Therefore, this study was designed to identify a novel lncRNA involved in KRASG12D-mutated CRC and to elucidate its molecular mechanisms. The analysis of differentially expressed lncRNAs in the GSE201412 dataset revealed that LINC02159 was significantly upregulated following treatment with the KRASG12D inhibitor MTRX1133 Data from the GTEx database indicated that LINC02159 is highly expressed in CRC tumour tissues and is associated with better patient outcomes. In vitro and in vivo experiments suggest that LINC02159 acts as a tumour suppressor in CRC progression. Specifically, LINC02159 knockdown negated the inhibitory effects of MRTX1133 on tumourigenesis and its promotive effect on ferroptosis in KRASG12D-mutated CRC cells. LINC02159 expression is regulated by METTL14, with METTL14 knockdown decreasing m6A methylation of LINC02159, leading to its increased expression in CRC cells. Additionally, LINC02159 stabilised FOXC2 expression through de-ubiquitination. Rescue experiments further clarified that the METTL14/LINC02159/FOXC2 signalling axis is crucial for the inhibitory effects of MRTX1133 in KRASG12D-mutated CRC. Our study provides novel insights into the therapeutic potential of MRTX1133 in treating KRASG12D-mutated CRC by identifying a METTL14/LINC02159/FOXC2 signalling axis that mediates drug response. Our findings highlight the importance of understanding the molecular mechanisms of lncRNAs in cancer to develop effective targeted therapies.

The identification of biomarkers correlated with colorectal cancer (CRC) prognosis holds substantial importance from both clinical and scientific perspectives. Zinc finger protein 26 (ZNF26) has not been previously investigated or documented in solid tumors; thus, further research is necessary to ascertain its prognostic value in CRC. Gene expression profiles and clinicopathological data were acquired from The Cancer Genome Atlas (TCGA) database. Subsequently, expression correlation was assessed utilizing the TCGA CRC cohort. The prognostic value of ZNF26 was evaluated through Kaplan-Meier (KM) and ROC curve analyses. Following this, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to perform enrichment analysis between high- and low-ZNF26 expression groups. The association between immune cells, immune checkpoint genes, and ZNF26 expression levels was examined. Lastly, the research findings were further validated using CRC tissue samples. The results revealed that, in comparison to healthy controls, CRC significantly reduced ZNF26 expression. Elevated ZNF26 expression was associated with poorer overall survival in CRC patients. Additionally, high ZNF26 expression exhibited an inverse relationship with the immunological score and immune checkpoint gene expression in CRC patients. The findings from the TCGA data analysis were corroborated by the PCR results obtained from CRC tissue samples. ZNF26 is markedly upregulated in colorectal cancer tissues, potentially serving as a biomarker for CRC.

Rectal cancer accounts for over 35% of the worldwide colorectal cancer burden representing a distinctive subset of cancers from those arising in the colon. Colorectal cancers exhibit a continuum of traits that differ with their location in the large intestine. Due to anatomical and molecular differences, rectal cancer is treated differently from colon cancer, with neoadjuvant chemoradiotherapy playing a pivotal role in the control of the locally advanced disease. However, radioresistance remains a major obstacle often correlated with poor prognosis. Multifunctional nanomedicines offer a promising approach to improve radiotherapy response rates, as well as to increase the intratumoral concentration of chemotherapeutic agents, such as 5-Fluorouracil. Here, we revise the main molecular differences between rectal and colon tumors, exploring the complex orchestration beyond rectal cancer radioresistance and the most promising nanomedicines reported in the literature to improve neoadjuvant therapy response rates.

Adenomatous colorectal polyps require endoscopic resection, as opposed to non-adenomatous hyperplastic colorectal polyps. This study aims to evaluate the effect of artificial intelligence (AI)-assisted differentiation of adenomatous and non-adenomatous colorectal polyps at CT colonography on radiologists' therapy management.

Five board-certified radiologists evaluated CT colonography images with colorectal polyps of all sizes and morphologies retrospectively and decided whether the depicted polyps required endoscopic resection. After a primary unassisted reading based on current guidelines, a second reading with access to the classification of a radiomics-based random-forest AI-model labelling each polyp as "non-adenomatous" or "adenomatous" was performed. Performance was evaluated using polyp histopathology as the reference standard.

77 polyps in 59 patients comprising 118 polyp image series (47% supine position, 53% prone position) were evaluated unassisted and AI-assisted by five independent board-certified radiologists, resulting in a total of 1180 readings (subsequent polypectomy: yes or no). AI-assisted readings had higher accuracy (76% +/- 1% vs. 84% +/- 1%), sensitivity (78% +/- 6% vs. 85% +/- 1%), and specificity (73% +/- 8% vs. 82% +/- 2%) in selecting polyps eligible for polypectomy (p < 0.001). Inter-reader agreement was improved in the AI-assisted readings (Fleiss' kappa 0.69 vs. 0.92).

AI-based characterisation of colorectal polyps at CT colonography as a second reader might enable a more precise selection of polyps eligible for subsequent endoscopic resection. However, further studies are needed to confirm this finding and histopathologic polyp evaluation is still mandatory.

Question This is the first study evaluating the impact of AI-based polyp classification in CT colonography on radiologists' therapy management. Findings Compared with unassisted reading, AI-assisted reading had higher accuracy, sensitivity, and specificity in selecting polyps eligible for polypectomy. Clinical relevance Integrating an AI tool for colorectal polyp classification in CT colonography could further improve radiologists' therapy recommendations.

Colorectal cancer (CRC) remains one of the leading causes of cancer-related morbidity and mortality around the world. Despite advances in surgery, chemotherapy, and targeted therapies, the prognosis for patients with metastatic or advanced CRC remains poor. Immunotherapies comprising immune checkpoint inhibitors showed disappointing responses in metastatic CRC (mCRC). However, cellular immunotherapy, specifically using classical dendritic cells (cDCs), may hold unique promise in immune recognition for CRC antigens. cDCs are substantial players in immune recognition and are instrumental in orchestrating innate and adaptive immune responses by processing and presenting tumor antigens to effector cells. Natural killer T (NKT) cells are insufficiently studied but unique effector cells because of their ability to bridge innate and adaptive immune reactions and the crosstalk with dendritic cells in cancer. This review explores the therapeutic potential of using both cDCs and NKT cells as a synergistic therapy in CRC, focusing on their biological roles, strategies for harnessing their capabilities, clinical applications, and the challenges within the tumor microenvironment. Both cDCs and NKT cells can be used as a new effective approach for cell-based therapies in cancers to provide a new hope for CRC patients that are challenging to treat.

Colorectal cancer (CRC) remains one of the most common causes of cancer-related mortality worldwide. Its progression is influenced by complex interactions involving genetic, epigenetic, and environmental factors. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), have been identified as key regulators of gene expression, affecting diverse biological processes, notably programmed cell death (PCD).

This review aims to explore the relationship between ncRNAs and PCD in CRC, focusing on how ncRNAs influence cancer cell survival, proliferation, and treatment resistance.

A comprehensive literature analysis was conducted to examine recent findings on the role of ncRNAs in modulating various PCD mechanisms, including apoptosis, autophagy, necroptosis, and pyroptosis, and their impact on CRC development and therapeutic response.

ncRNAs were found to significantly regulate PCD pathways, impacting tumor growth, metastasis, and treatment sensitivity in CRC. Their influence on these pathways highlights the potential of ncRNAs as biomarkers for early CRC detection and as targets for innovative therapeutic interventions.

Understanding the involvement of ncRNAs in PCD regulation offers new insights into CRC biology. The targeted modulation of ncRNA-PCD interactions presents promising avenues for personalized cancer treatment, which may improve patient outcomes by enhancing therapeutic effectiveness and reducing resistance.

Background/Objectives: The certification of hospitals as colorectal cancer centers aims to improve treatment quality, but evidence supporting its effectiveness remains limited. This study evaluated the impact of certification on treatment outcomes for rectal cancer patients in Germany. Methods: We conducted a retrospective analysis of 14,905 patients with primary rectal cancer (UICC Stages I-III) treated at 271 hospitals. Treatment outcomes were compared between certified colorectal cancer centers (3624 patients in 55 hospitals) and non-certified hospitals (11,281 patients in 216 hospitals). Additionally, a subset analysis examined outcomes before and after certification within the same institutions. Results: Certified centers demonstrated higher utilization of preoperative imaging (endorectal ultrasound: 70.7% vs. 58.2%, p < 0.001; pelvic MRI: 39.1% vs. 28.5%, p < 0.001) and lower rates of intraoperative complications (4.6% vs. 6.2%, p < 0.001). Surgical quality indicators, including M.E.R.C.U.R.Y. classification (Grade 1: 86.5% both groups, p = 0.620) and anastomotic leakage rates (11.3% vs. 11.9%, p = 0.407), were comparable between certified and non-certified hospitals. Despite treating patients with more favorable tumor stages, certified centers showed no significant advantage in 5-year overall survival (82.8% vs. 82.0%, p = 0.880) or 30-day mortality (2.6% both groups, p = 0.869). Hospital stays were marginally shorter in certified centers (19.46 vs. 20.24 days, p < 0.001). Conclusions: While certification was associated with improved adherence to diagnostic protocols and reduced intraoperative complications, it did not significantly impact surgical quality or long-term survival outcomes. These findings suggest that certification alone may not guarantee superior treatment quality, as hospitals participating in quality assurance programs achieved comparable results without formal certification.

The large and rapid increase in the incidence and mortality of colorectal cancer (CRC) demonstrates the urgent need for new drugs with higher efficacy to treat CRC. However, the lack of applicable and reliable preclinical models significantly hinders the progress of drug development. Patient-derived xenograft (PDX) models are currently considered reliable in vivo preclinical models for predicting drug efficacy in cancer patients. This study successfully uses the CRC PDX model to develop clinical indications for the new multi-target kinase inhibitor BPR1J481 and demonstrated the anti-cancer mechanism and competitive advantages of this drug candidate. The results demonstrate that BPR1J481 exhibits significant anticancer efficacy by inducing apoptosis in CRC PDX tumor tissues and corresponding PDX-derived CRC cells. Through kinase competitive binding and kinase activity assays, we discover that BPR1J481 effectively inhibits SRC kinase activity by directly binding to its active site. The reduction in SRC phosphorylation observed in CRC PDX tumor tissues and derived cells upon treatment with BPR1J481 further validates its inhibitory potential. Furthermore, the decrease in viable cells after SRC knockout and the poorer prognosis observed in patients with higher SRC expression, emphasizes the critical significance and clinical relevance of SRC in CRC. Additionally, BPR1J481 exhibits robust anti-angiogenic effects by suppressing VEGF- and PDGF-induced endothelial cell proliferation, migration, and capillary-like tube formation through inhibition of VEGFR2 and PDGFRβ phosphorylation. Remarkably, BPR1J481 appears to demonstrate greater efficacy against CRC compared to regorafenib. These findings highlight the therapeutic potential of BPR1J481 for patients with CRC.

The tumorigenesis of colorectal cancer (CRC) often follows the normal-adenoma-carcinoma (N-A-C) sequence. However, the molecular mechanisms underlying colorectal adenoma carcinogenesis remain largely unknown. Here, we analyzed transcriptomic profile changes in normal, advanced adenoma, and carcinoma tissues from patients with CRC, revealing that glutamic-pyruvic transaminase 1 (GPT1) in colorectal tissues was down-regulated during the N-A-C process and correlated with poor CRC prognosis. Mechanistically, GPT1 was transcriptionally activated by Krüppel-like factor 4 (KLF4). GPT1 reprogrammed metabolism and suppressed CRC tumorigenesis in cells and mouse models not only through enzyme-dependent α-ketoglutarate (α-KG) production and WNT signaling inhibition but also through enzyme-independent disruption of the folate cycle through binding with methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L). Furthermore, we identified poliumoside as a GPT1 activator that restrained CRC progression in cells, patient-derived CRC organoids, and patient-derived xenograft (PDX) models of CRC. Our study uncovers a role for GPT1 in CRC tumorigenesis and shows that poliumoside is a potential drug for the prevention and treatment of CRC.

The applications of artificial intelligence (AI) and deep learning (DL) are leading to significant advances in cancer research, particularly in analysing histopathology images for prognostic and treatment-predictive insights. However, effective translation of these computational methods requires computational researchers to have at least a basic understanding of histopathology. In this work, we aim to bridge that gap by introducing essential histopathology concepts to support AI developers in their research. We cover the defining features of key cell types, including epithelial, stromal, and immune cells. The concepts of malignancy, precursor lesions, and the tumour microenvironment (TME) are discussed and illustrated. To enhance understanding, we also introduce foundational histopathology techniques, such as conventional staining with hematoxylin and eosin (HE), antibody staining by immunohistochemistry, and including the new multiplexed antibody staining methods. By providing this essential knowledge to the computational community, we aim to accelerate the development of AI algorithms for cancer research.

The occurrence of Colorectal Cancer (CRC) is influenced by various factors, including host susceptibility, immune imbalance, and environmental triggers. Numerous studies have underscored the critical role of chronic intestinal inflammation and dysbiosis in the development of CRC. Traditional Chinese Medicine (TCM) holds unique advantages in regulating the intricate process of and comprehensive treatment for systemic disease. Previous investigations by our team have confirmed the anti-cancer properties of the TCM compound ChanLingGao (CLG), including inhibiting cancer cell migration, and alleviating bone cancer pain. However, the mechanisms underlying its efficacy in alleviating chronic intestinal inflammation, modulating the gut microbiota, and protecting the intestinal mucosal barrier remain largely unknown.

This study aims to explore the inhibitory effects of CLG on CRC tumors in mice and its potential mechanisms.

A chronic inflammation-related CRC mouse model was established using AOM/DSS. The study examined the mechanisms of intestinal inflammation and tumor cell proliferation through intestinal histological morphology. High-throughput sequencing was employed to analyze changes in gut microbiota diversity and intestinal mucosal barrier integrity in CRC mice. Based on network pharmacology target prediction and Wnt/β-catenin signaling pathway analysis, the study analyzed and discussed the potential mechanisms of CLG on CRC.

CLG significantly ameliorated weight loss and increased survival rates in CRC mice, while suppressing tumor growth in the intestinal tract. Post-CLG treatment improved intestinal inflammation in CRC mice, with a significant reduction in inflammatory factors IL-6, IL-23 and LCN2, and inhibition of tumor cell proliferation markers Proliferating Cell Nuclear Antigen (PCNA), Recombinant Ki-67 Protein (Ki-67), and CCND1. 16sV3-V4 region microbiota sequencing results indicated that CLG improved dysbiosis, and significantly increased the abundance of Akkermansia bacteria, further promoting the expression of MUC-2 protein and mucin secretion. Additionally, CLG prevented the disruption of intestinal epithelial cell junction proteins Occludin, Claudin-1, ZO-1, and E-cadherin, restored the number of goblet cells, and preserved the integrity of the intestinal mucosal barrier. Further experiments suggested that CLG inhibited abnormal activation of the Wnt/β-catenin pathway, and its potential mechanism in maintaining mucosal barrier integrity might be related to blocking Wnt/β-catenin pathway.

This study demonstrates that CLG can inhibit CRC tumor growth by regulating the gut microbiota structure, reducing intestinal inflammation, improving intestinal mucosal barrier function, and inhibiting the complex process of cancer cell proliferation. This provides new clinical insights into the "membrane-oriented" treatment of CRC with CLG.

identification and removal of advanced adenomas (AA) reduce colorectal cancer (CRC) incidence and potentially mortality. CRC screening often uses fecal immunochemical testing to select high-risk individuals for colonoscopy, despite its low sensitivity for AA and relatively high false-positivity rate. Previous studies have linked proteases to CRC development through their ability to facilitate angiogenesis and immunoregulation. This study aims to identify colorectal neoplasia-associated proteases and their substrates as a potential noninvasive screening test, introducing an innovative application of fecal protease profiling, which has previously been limited to tissue samples.

eighteen fluorogenic substrates were designed based on literature. Proteolytic degradation of these substrates was measured in fecal samples of patients with CRC (n = 12), AA (n = 9), nonadvanced adenomas (n = 10), and controls (n = 14). Substrate degradation was correlated to a matched human proteome data set, and underlying proteases were identified based on their recognition patterns. Experiments with protease inhibitors and ZnCl2 were performed to further characterize the involved proteases.

in total, 7 of the 18 substrates tested showed a significantly decreased proteolytic degradation in feces from patients with any colorectal neoplasia compared to the control group. The l-aspartic acid-l-glutamic acid substrate (ED) showed significantly decreased degradation in AA and CRC patients. ED degradation significantly decreased with the addition of ZnCl2 and the cysteine protease inhibitor NEM.

we successfully developed colorectal neoplasia-specific fluorogenic substrates, highlighting the ED substrate as a potential substrate for the detection of AA and CRC. Although the responsible proteases require further identification, our results suggest an association with calcium-dependent cysteine proteases.

Microsatellite instability-high (MSI-high) tumors comprise ~15% of sporadic colorectal cancers (CRC) and are associated with elevated T cell infiltration. However, the universality of this response across T cell subtypes with distinct functions is unknown.

Including 1,236 CRC tumors from three observational studies, we conducted in-situ T cell profiling using a customized 9-plex (CD3, CD4, CD8, CD45RA, CD45RO, FOXP3, KRT, MKI67, and DAPI) multispectral immunofluorescence assay. MSI status was assessed through polymerase chain reaction or immunohistochemical assays. We used multivariable ordinal logistic regression to estimate odds ratios (OR per increasing quantile) and 95% confidence intervals (CIs) for the association of MSI status with quantiles of T cell densities in either tumor epithelial or stromal tissue areas.

Compared to microsatellite instability low or microsatellite stable (MSI-low/MSS) tumors, MSI-high status was associated with higher density for the majority of immune subsets (twelve out of eighteen) in both epithelial and stromal tissue areas. The strongest associations were for CD3+CD8+ T cells in epithelial areas [OR (95% CI) for naive, memory, and regulatory subsets = 3.49 (2.57, 4.75); 2.82 (2.10, 3.78); 3.04 (2.24, 4.13), respectively]. Conversely, stromal area CD3+CD4+ memory T cells were inversely associated [OR (95% CI) = 0.68 (0.51, 0.91)].

MSI-high status was strongly associated with higher densities of most T cell subsets in both epithelial and stromal tissue areas. Our investigation supports efforts to identify patients who may be more likely to respond to current immunotherapy treatments.

This study helps us better understand how a clinically relevant tumor phenotype, microsatellite instability status, is related to different functioning T cell densities in colorectal tumors, which may impact future immunotherapy strategies.

Early detection of colorectal cancer (CRC) is crucial for improving the survival rates of patients.

We aimed to develop a novel strategy for early CRC detection using the fragmentomic features of circulating cell-free mitochondrial DNA (ccf-mtDNA).

Here, a total of 1147 participants, including 478 healthy controls (HCs), 112 patients with advanced adenomas (AAs) and 557 patients with CRC, were enrolled from five hospitals and plasma samples were collected for capture-based ccf-mtDNA sequencing.

Our data analysis revealed significantly aberrant ccf-mtDNA fragmentomic features in patients with CRC and AA when compared with HCs. Then, a CRC detection (CD) model was constructed based on the fragmentomic features of ccf-mtDNA from 246 patients with CRC and 168 HC in the training cohort, showing area under the curve of 0.9863, sensitivity of 92.68% and specificity of 93.45%. Both internal and two external validation cohorts demonstrated the excellent capacity of CD model in distinguishing patients with early-stage CRC from HCs, greatly surpassing the performance of serum biomarkers. Furthermore, our CD model can also detect patients with AA with a sensitivity of 79.35% in AA cohort 1 and 85.00% in AA cohort 2.

In conclusion, based on aberrant ccf-mtDNA fragmentomic features, a novel and non-invasive approach was established for the detection of patients with early-stage CRC or AA, with high performance.

Bleeding per rectum (BPR) is a common clinical presentation, and colonoscopy is the gold standard for evaluating patients aged ≥ 45 years. However, its role in younger patients remains unclear. This study evaluated the appropriateness of colonoscopy in patients < 40 years of age who presented with BPR.

This retrospective observational study was conducted over 10 years, including 3422 patients aged 18-40 years who underwent colonoscopy for BPR. The cohort was divided into two age groups: younger (aged 18-30 years) and older (31-40 years). The patients' baseline characteristics, colonoscopy findings, and histopathological results were analyzed.

Hemorrhoids were the most common finding (48%), with a higher prevalence in younger age groups (50.7%). Polyps were detected in 12.5% of patients, with 1.75% having advanced adenoma polyps (AAP) and 1.3% diagnosed with colorectal cancer (CRC). A family history of CRC/AAP was significantly associated with increased CRC risk (adjusted OR 6.35, 95% CI 2.24-18.02, p = 0.001) in explorative logistic regression analysis.

AAP and CRC were detected in a small but significant proportion of patients, particularly among those aged 18-30 years. The detection of significant lesions in this age group highlights the need for targeted colonoscopy based on specific risk factors such as family history and clinical presentation. Future research should prioritize the creation of targeted assessment models to improve clinical decision making in this context.

Colorectal cancer is one of the most prevalent forms of cancer globally. The most common routine diagnostic methods are the examination of the interior of the colon during colonoscopy or sigmoidoscopy, which frequently includes the removal of a biopsy sample. Optical methods, such as Raman spectroscopy (RS) and optical coherence tomography (OCT), can help to improve diagnostics and reduce the number of unnecessary biopsies. For in vivo use, we have developed fiber-optic probes, one for single-point Raman measurements and one for volumetric OCT. Here, we present the results of a clinical study using these fiber-optic probes in an ex vivo setting. The goal was to evaluate the beneficial effect of combining these two modalities on the AUC ROC score of the machine learning models for the discrimination of cancerous and healthy tissue. In the initial stage of the investigation, both modalities were validated separately using linear discriminant analysis. RS was subjected to spectral preprocessing, while OCT underwent texture feature extraction. Subsequently, both modalities were integrated using the Bayes rule, resulting in an enhanced area under the curve score of 0.93, representing an improvement over the 0.77 score for Raman spectroscopy and 0.86 for OCT.