Targeted therapies leveraging the innate immune system are emerging as promising cancer treatments. The mitochondrial antiviral signaling protein (MAVS) plays a crucial role in initiating innate immune responses, but its clinical use is limited by the risk of uncontrolled activation and systemic toxicity. To address this, we developed a novel therapeutic agent, the truncated interferon activation switch (TRIAS), combining MAVS truncates with a tumor antigen-targeting single-chain variable fragment (scFv). This design ensures antigen-dependent, controlled activation. Lentiviral delivery of TRIAS induced significant antitumor responses, including complete tumor regression in some cases. Flow cytometry (FCM) analysis further confirmed that tumor cells were the predominant population expressing the transgene. TRIAS-expressing tumor cells exhibited enhanced antitumor activity, likely due to increased cytokine release and upregulated major histocompatibility complex (MHC) expression, enabling tumor cells to function as antigen-presenting cells. This activated other immune cells, driving adaptive immune responses. Additionally, TRIAS promoted a proinflammatory shift in the tumor microenvironment (TME). In conclusion, TRIAS was validated as an innovative immunotherapeutic agent with MAVS-like immune-activating properties and tightly controlled mechanisms, offering a safer and more effective approach for clinical cancer immunotherapy.

The initiation and progression of colorectal cancer (CRC) are intimately associated with genetic, environmental and biological factors. Desulfovibrio vulgaris (DSV), a sulfate-reducing bacterium, has been found excessive growth in CRC patients, suggesting a potential role in carcinogenesis. However, the precise mechanisms underlying this association remain incompletely understood. We have found Desulfovibrio was abundant in high-fat diet-induced Apcmin/+ mice, and DSV, a member of Desulfovibrio, triggered colonocyte proliferation of germ-free mice. Furthermore, the level of DSV progressively rose from healthy individuals to CRC patients. Flagella are important accessory structures of bacteria, which can help them colonize and enhance their invasive ability. We found that D. vulgaris flagellin (DVF) drove the proliferation, migration, and invasion of CRC cells and fostered the growth of CRC xenografts. DVF enriched the epithelial-mesenchymal transition (EMT)-associated genes and characterized the facilitation of DVF on EMT. Mechanistically, DVF induced EMT through a functional transmembrane receptor called leucine-rich repeat containing 19 (LRRC19). DVF interacted with LRRC19 to modulate the ubiquitination of tumor necrosis factor receptor-associated factor (TRAF)6, rather than TRAF2. This interaction drove the ubiquitination of pivotal molecule TAK1, further enhancing its autophosphorylation and ultimately contributing to EMT. Collectively, DVF interacts with LRRC19 to activate the TRAF6/TAK1 signaling pathway, thereby promoting the EMT of CRC. These data shed new light on the role of gut microbiota in CRC and establish a potential clinical therapeutic target.

Despite extensive investigations into the microbiome and metabolome changes associated with colon polyps and colorectal cancer (CRC), the microbiome and metabolome profiles of individuals with colonic polyposis, including those with (Gene-pos) and without (Gene-neg) a known genetic driver, remain comparatively unexplored. Using colon biopsies, polyps, and stool from patients with Gene-pos adenomatous polyposis (N = 9), Gene-neg adenomatous polyposis (N = 18), and serrated polyposis syndrome (SPS, N = 11), we demonstrated through 16S rRNA sequencing that the mucosa-associated microbiota in individuals with colonic polyposis is representative of the microbiota associated with small polyps, and that both Gene-pos and SPS cohorts exhibit differential microbiota populations relative to Gene-neg polyposis cohorts. Furthermore, we used these differential microbiota taxa to perform linear discriminant analysis to differentiate Gene-neg subjects from Gene-pos and from SPS subjects with an accuracy of 89% and 93% respectively. Stool metabolites were quantified via 1H NMR, revealing an increase in alanine in SPS subjects relative to non-polyposis subjects, and Partial Least Squares Discriminant Analysis (PLS-DA) analysis indicated that the proportion of leucine to tyrosine in fecal samples may be predictive of SPS. Use of these microbial and metabolomic signatures may allow for better diagnostric and risk-stratification tools for colonic polyposis patients and their families as well as promote development of microbiome-targeted approaches for polyp prevention.

FLASH radiotherapy, which involves the delivery of an ultra-high radiation dose rate exceeding 40 Gy/s, has emerged as a promising tumor ablation strategy. While this approach generally spares normal tissues, the incomplete killing of tumors may sometimes lead to recurrence due to the immunosuppressive tumor microenvironment (TME). Herein, an aggregation-induced-emission luminogen (AIEgen)-alginate hydrogel was used to sensitize colon cancer via photodynamic therapy (PDT). Flower-like calcium carbonate nanoparticles, doped with an AIEgen termed CQu, were designed and applied as a cocktail with sodium alginate. When exposed to the acidic TME, Ca2+ is released from this structure, resulting in sodium alginate termed FA forming a hydrogel in situ within the TME. This hydrogel also captures high concentrations of CQu in the local TME. Under laser irradiation, the CQu can generate sustained reactive oxygen species (ROS) production, thereby facilitating Ca2+ influx and causing mitochondrial damage. Through a single injection of established FA hydrogel, followed by PDT and FLASH radiotherapy, immunogenic tumor cell death was induced which promoted antitumor immunity, thereby protecting against tumor recurrence while realizing abscopal effect. The results highlight the potential to improve the sensitivity of tumor cells to FLASH radiotherapy through sustained ROS production and Ca2+ overload, thereby yielding optimal immunotherapy outcomes.

Colorectal cancer is a major global health burden, with significant heterogeneity in clinical outcomes among patients. Identifying robust prognostic gene expression signatures can help stratify patients, guide treatment decisions, and improve clinical management. This review provides an overview of current prognostic gene expression profiles in colorectal cancer research. We have synthesized evidence from numerous published studies investigating the association between tumor gene expression patterns and patient survival outcomes. The reviewed literature reveals several promising gene signatures that have demonstrated the ability to predict disease-free survival and overall survival in CRC patients, independent of standard clinicopathological risk factors. These genes are crucial in fundamental biological processes, including cell cycle control, epithelial-mesenchymal transition, and immune regulation. The implementation of prognostic gene expression tests in clinical practice holds great potential for enabling more personalized management strategies for colorectal cancer.

Early-onset colorectal cancer (EOCRC) is an alarming entity worldwide. Yet, stage-specific characteristics and prognosis in localized and synchronous metastatic EOCRC are not well-defined. Two cohorts of CRC patients (localized and synchronous metastatic) were evaluated, defining EOCRC as the diagnosis <50 years old. Five hundred sixty-eight patients were included (n = 432 localized, 14.4% [n = 62] EOCRC and n = 136 synchronous metastatic, 20.6% [n = 28] EOCRC). 93.5% of localized and 96.5% of synchronous metastatic EOCRC patients were symptomatic at diagnosis. Among localized patients, female gender (58.1% vs. 40%, p = .008), perineural invasion (41.9% vs. 24.9%, p = .005), folinic acid, 5-fluorouracil, and oxaliplatin chemotherapy (45.2% vs. 25.2%, p = .003), and perioperative chemotherapy cycles (9.21 [± 3.10] vs. 7.98 [± 2.92], p = .006) were higher in EOCRC compared with ≥50-year. Median recurrence-free survival (RFS) and overall survival were not reached in either group (p = .234 and p = .831). Only RAS mutant status was associated with RFS (Hazard ratio: 7.09 [95% confidence interval (CI): 1.87-26.76], p < .001) in EOCRC. Among synchronous metastatic patients, urgent surgery (32.1% vs. 11.1%, p = .014) and local treatments (39.3% vs. 20.4%, p = .037) were more frequent in EOCRC. Median progression-free survival and overall survival in the EOCRC and ≥50 years were 8.07 months (95% CI: 5.03-12.97) vs. 10.03 months (95% CI, 8.40-13.10) (p = .450) and 18.57 months (95% CI, 13.33-43.03) vs. 19.83 months (95% CI, 16.07-27.30) (p = .833), respectively. Synchronous metastatic EOCRC more frequently underwent urgent surgery (32.1% vs. 8%, p = .008) and had RAS mutation (43.5% vs. 16.7%, p = .032) than localized EOCRC. This study suggests that localized and synchronous metastatic EOCRC patients may have different characteristics than average onset, without survival differences. Implementation of stage-specific characteristics into daily practice is necessary for decision-making processes in these young patients.

Studies aimed to evaluate the expected impact of alternative screening strategies are essential for optimizing colorectal cancer (CRC) screening offers, but such studies are lacking in Germany, where two screening colonoscopies (CS) 10 years apart are offered for men from age 50 and women from age 55. Our aim was to explore whether and to what extent the efficacy of utilizing two CS could be enhanced by alternative starting ages and screening intervals. We modeled the expected numbers of CRC cases, CRC deaths, years of potential life lost (YPLL), and disability-adjusted life years (DALYs) due to CRC in hypothetical cohorts of 100,000 men and women aged 45-85 using COSIMO, a validated Markov-based multi-state simulation model. Modeled strategies included combinations of starting ages (45/50/55/60) and CS (10/15/20 years). For men, CRC deaths could be slightly reduced by extending the interval to 15 years, with a second CS at 65. YPLL and DALYs would be reduced by decreasing starting age to 45 when combined with a 15-year screening interval. For women, use of two CS at ages 50 and 65 would reduce all CRC burden parameters compared to the current earliest-use offer at 55 and 65 years. Our results suggest that lowering the starting age of screening colonoscopy to 45 for men and 50 for women, combined with extending the CS screening interval to 15 years would have the potential to enable significant reductions in years of potential life lost, and disability-adjusted life years compared to current screening offers in Germany.

Epidermal growth factor-like proteins (EGFLs) contain more than a single EGF/EGF-like domain within their protein structure. To date, ten EGFL family members (EGFL1-10) have been characterized across diverse tissues and developmental stages under different conditions. In this review, we conclude that EGFLs are instrumental in regulating biological activities and pathological processes. Under physiological conditions, EGFLs participate in angiogenesis, neurogenesis, osteogenesis, and other processes. Under pathological conditions, EGFLs are linked with different diseases, particularly cancers. Furthermore, we highlight recent advancements in the study of EGFLs in biological conditions and cancers. In addition, the regulatory role and key underlying mechanism of EGFLs in mediating tumorigenesis are discussed. This paper also examines potential antagonists that target EGFL family members in cancer therapeutics. In summary, this comprehensive review elucidates the critical role of EGFLs in neoplastic diseases and highlights their potential as therapeutic targets.

Colorectal cancer (CRC) is the third most common cancer worldwide and there is a controversy regarding the influence of laxative use on the incidence of CRC. Therefore, the present study aimed to investigate the effects of laxative use and different subtypes of laxatives on the incidence of CRC. To this aim, a comprehensive search of three databases (PubMed, Embase and the Cochrane Library) was conducted on April 12, 2022, using key words that included 'laxative' and 'CRC', which initially retrieved 305 records. Ultimately, 12 studies involving 415,313 patients met all eligibility criteria and were included in a meta-analysis. Subsequently, patients were categorized into the laxative use and non-laxative use groups. Stata 16.0 software was used for all data analyses. The results indicated that laxative use was not significantly associated with CRC risk [odds ratio (OR), 0.95; 95% confidence interval (CI), 0.75-1.20; P=0.65; I2=94.63%]. In the subgroup analyses, the effects of different laxative types were further examined. Notably, all types of laxatives except for fiber laxatives showed no significant influence on CRC risk (P>0.1). By contrast, fiber laxatives were associated with a reduced risk of CRC (OR, 0.74; 95% CI, 0.59-0.93; P=0.01; I2=32.15%), suggesting a potential protective effect of this medication. In conclusion, the findings of the present study suggest that the use of laxatives does not increase the risk of CRC. Moreover, the use of fiber laxatives may have a protective effect by reducing CRC incidence.

Colorectal cancer is the third most common cancer worldwide, accounting for approximately 10 % of all cancer cases. It is also the second leading cause of cancer-related deaths globally. Phloretin is a natural compound found in apples and other fruits. It has been studied for its potential health benefits, including antioxidant and anti-inflammatory properties. However, more research is needed to fully understand its impact on cancer prevention or treatment. This article aimed to prepare phloretin-nanospanlastics (Ph-NSLs) to evaluate their effects on dimethylhydrazine (DMH)-induced colon cancer in mice.

Morphology, Particle size, zeta potential, UV-vis, entrapment efficiency, polydispersity index, FT-IR spectra, and drug release of phloretin and Ph-NSLs at pH 6.8.were described. Ph-NSLs were also tested for their anti-cancer properties in DMH-induced colon cancer in mice. A 36 mice were divided into 6 groups; Normal control, DMH (20 mg/k.g.b.w.), DMH + Ph-NSLs (25 mg/k.g.b.w.), DMH + Ph-NSLs (50 mg/k.g.b.w.), DMH + 5-FU(20 mg/k.g.b.w.), DMH + Ph-NSLs (50 mg), 5-FU (20 mg). Ph-NSLs were tested for their anticancer properties in DMH-treated mice by evaluating the IC50, viability and inhibitory values of Ph-NSLs against Caco-2. Also, the effect of Ph-NSLs administration on number of surviving mice, number of tumors/mice, average of tumor size, Hb, RBCs, WBCs, C19-9, MDA, GSH, SOD, IL-2, TNF-α, TGF-β1, CEA, and P53 levels in mice treated DMH were estimated.

The synthesized Ph-NSLs were uniform, spherically shaped, and well dispersed, with a size, entrapment efficiency, and polydispersity index of approximately 114.06 ± 8.35 nm, 78.60 %, and 0.05, respectively. The zeta potential value of Ph-NSLs was measured at -21.5 ± 1.47 mV. Zeta potential reflects the surface charge of nanoparticles and affects their stability and interactions. UV spectra of phloretin and Ph-NSLs showed strong absorption peaks at 225 and 285 nm. These peaks correspond to specific wavelengths where the compound absorbs light. The percentage of Ph- NSLs release was found to be 56.87 ± 2.45 %. IC50 of Ph-NSLs was recorded 15.76 ± 0.42 μg/ml and the viability and inhibitory values of Ph-NSLs against Caco-2 cell lines was resorded 2.39, and 97.61 %, respectively at 100 μg/ml as well as 10.3, and 89.7 %, respectively at 50 μg/ml.Moreover, The combination of 5-FU and Ph-NSLs resulted in a moderate increase in survival and significantly reduces tumor size and number, showing enhanced anticancer efficacy compared to individual treatments as well as attenuated levels of hemoglobin (Hb), red blood cells (RBCs), and white blood cells (WBCs). Reduced plasma cancer antigen 19-9 (CA19-9) levels as well as improved of colon malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), interleukine-2 (IL-2), tumor necrosis factor-alpha (TNF-α), tumor growth factor-beta1 (TGF-β1), carcinoembryonic antigen (CEA), and tumor protein (P53) levels. Also, Ph-NSLs and 5FU, either alone or together, decreased the expression of the Akt and PI3K genes in the colon. The combination of Ph-NSLs and 5FU showed more pronounced anticancer activity than Ph-NSLs administered individually.

The combination of 5-FU and Ph-NSLs significantly enhances anticancer efficacy, reducing both the number of tumors and average tumor size more effectively than either treatment alone. This synergistic effect leverages 5-FU's inhibition of DNA synthesis and phloretin's induction of apoptosis and inhibition of cell proliferation, offering a promising approach for improved cancer treatment outcomes.

Carcinoembryonic antigen (CEA) is a broad-spectrum biomarker, and its accurate detection and analysis is important for early clinical diagnosis and treatment. This study aimed to develop a highly sensitive and selective sandwich-type immunosensor based on electrochemical impedance spectroscopy (EIS) for the accurate detection of CEA. A novel composite material, gold nanoparticle/reduced-graphene oxide/graphitic carbon nitride (AuNPs/rGO/g-C3N4), was synthesized with excellent electrical conductivity and a large specific surface area to immobilize biological probes. And ab1-CEA-ab2 formed a sandwich structure of 'antibody-antigen-antibody', which ensured the high selectivity of the biosensor. Furthermore, the introduction of caprolactone polymer (DMPA-PCL) significantly amplifies the impedance signal and improves the sensitivity of the analytical method. Scanning electron microscopy, x-ray diffraction, transmission electron microscopy Fourier transform infrared spectroscopy, and ultraviolet-visible spectrophotometry were used to characterise the prepared AuNPs/rGO/g-C3N4 and DMPA-PCL. Under the optimal conditions, the sensor showed good analytical performance for the detection of CEA with a linear range of 100 fg mL-1-100 ng mL-1 and a detection limit of 83.2 fg mL-1. And the sandwich-type immunosensor showed good selectivity and stability for the recognition of CEA in real samples.

Natural cytotoxic peptides (NCPs) are emerging sources of novel anticancer chemotherapeutics. Especially, Melittin, which is the major component of bee venom and the first-in-class NCP, has been considered as a promising anticancer scaffold. Nevertheless, as a classical linear, cationic, amphipathic, and membrane-lytic peptide, Melittin may be easily degraded by proteases, suffering from poor stability, moderate anticancer durability, and severe hemolysis. In this study, applying the terminal modification and hybridization strategies, ten Melittin-based derivatives were designed, synthesized, and investigated for their anticancer potential. The robust and economic synthetic method, in vitro anticancer efficiency, time-kill kinetics, serum stability, anti-migration activity, hemolysis effects, and anticancer mechanism were explored. As expected, the Melittin-based derivatives exhibited highly potent cytotoxicity against all six tested cancer cell lines. In particular, compared with natural Melittin, the derived peptides LJ-5 containing both N-terminal acetylation and C-terminal hydrazidation, and LJ-6, the methotrexate MTX-GFLG-Melittin conjugate exhibited significantly improved proteolytic stability, more durable anticancer efficiency, higher anti-migration activity, as well as reduced hemolysis effects. Besides, it was further verified that LJ-5 and LJ-6 could efficiently disrupt the integrity of cancer cell membrane, localize to the mitochondria and rapidly reduce the mitochondrial membrane potential of cancer cells. Collectively, the economic synthetic method and stability-guided optimization were conducted on Melittin, affording hydrolysis-resistant LJ-5 and LJ-6 that may serve as anticancer candidates and useful references for further optimizations of cytotoxic peptides.

Although E-cadherin is known as a tumor suppressor via its effects on cell to cell adhesion, the effects of E-cadherin on malignant transformation have not yet been thoroughly investigated. In the present study, after malignant transformation was induced by spheroid formation in a fetal bovine serum-supplemented environment, the effects of soluble E-cadherin on the spheroidogenesis of colorectal cancer cells were investigated. E-cadherin knock-out (KO) was performed in HCT116 cells, targeting exon 3 of the CDH1 gene. A cell viability assay was performed to determine the proliferation and viability of wild type and CDH1 KO HCT116 cells after treatment with anticancer drugs. Spheroidogenesis was compared with or without exogenous E-cadherin, antibody against the ectodomain of E-cadherin (DECMA-1) and PD98059 treatment. In addition, morphometry, immunocytochemistry and western blotting were performed. Soluble E-cadherin in culture media was measured using an enzyme-linked immunosorbent assay. Firstly, CDH1 KO was confirmed by western blotting. Notably, the proliferation and viability of cells following treatment with 5-fluorouracil, epidermal growth factor receptor inhibitor and src kinase inhibitor were similar between the cell lines. Exogenous E-cadherin or DECMA-1 treatment did not affect spheroidogenesis, although long-term maintenance was slightly disturbed in CDH1 KO spheroids compared with that in wild type spheroids. In addition, E-cadherin was increased in spheroid culture as compared with that in conventional culture. Soluble E-cadherin was increased in a time-dependent manner, particularly in wild type HCT116 cells. PD98059 inhibited ERK activation and enhanced E-cadherin expression in conventional culture without affecting spheroidogenesis. These results suggested that soluble E-cadherin may be considered as a biomarker for colorectal cancer, although exogenous E-cadherin might not have a further role in malignant transformation.

The definitive treatment of stage-III colon cancer is surgery and adjuvant chemotherapy. A combined assessment of pre-operative and post-adjuvant chemotherapy carcinoembryonic antigen (CEA) levels may better prognosticate early recurrence and survival.

A cohort of patients who underwent surgery and adjuvant chemotherapy was assessed. The CEA-Square (CEA2) score was defined as the multiplication of preoperative and post-adjuvant chemotherapy CEA levels and was grouped as "≤25(ng/mL)2" and ">25(ng/mL)2.

Among the 432 patients,137 were eligible. CEA2 score (>25 vs ​≤ ​25 (ng/mL)2) was significantly prognostic for early recurrence (34.5 ​% vs. 14.3 ​%, log-rank, p ​< ​0.001). In the multivariable analysis, only the CEA2 score remained associated with early recurrence [HR:3.375, (95 ​% CI:1.488-7.655), p ​= ​0.004]. In a median follow-up of 37.5 months (2.5-101.0), a high CEA2 score [>25 (ng/mL)2] was significantly associated with a worse OS (log-rank, p ​< ​0.001).

CEA2 is a simple, practical score combining prognostic values of preoperative and post-adjuvant chemotherapy CEA levels.

Upper age limits are currently fixed for all fecal immunochemical test (FIT)-based colorectal cancer (CRC) screening programs. A risk-stratified upper age limit may be beneficial. Therefore, we assessed differences in interval CRC risk among individuals who had reached the upper age limit of screening (75 years). Individuals with a negative FIT (<47 μg Hb/g feces) in the final round of the Dutch CRC screening program were selected from the national screening database and linked to the national cancer registry to identify CRCs diagnosed within 24 months (interval CRCs). Survival analyses assessed whether sex and last fecal hemoglobin (f-Hb) concentration were associated with interval CRC risk. A multivariable logistic regression assessed whether sex, last f-Hb concentration and screening round were associated with stage distribution (early vs. late). Last f-Hb concentrations were considered detectable when they were >0 μg Hb/g feces. Among 305,761 individuals with a complete follow-up (24 months), 661 were diagnosed with interval CRC (21.6 per 10,000 negative FITs). Individuals with detectable f-Hb (15%) were 5 times more likely to be diagnosed with interval CRC than those without (HR 4.87, 95%CI: 4.19-5.65). Moreover, their cancers were more often detected at a late stage compared to individuals without detectable f-Hb (OR 1.45, 95%CI: 1.06-2.01). Our results show that interval CRC risk among individuals aged ≥75 differs substantially by last f-Hb concentration, indicating a uniform age to stop screening is suboptimal. Future research, taking into account multiple screening rounds and FIT results, should determine the optimal risk-stratified screening strategy.

Altered lipid metabolism is a well-known hallmark of cancer. However, the underlying mechanisms of altered lipid metabolism in colorectal cancer (CRC) progression requires further investigation. Previously we have revealed that DEAD-box RNA helicase 21 (DDX21) promotes CRC metastasis via liquid-liquid phase separation. In this study, we identify DDX21 as a novel regulator of lipid metabolism in CRC.

In vitro and in vivo assays illustrated the biological role of DDX21 and YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) in CRC lipid metabolism and progression. Bioinformatics analysis, ChIP, meRIP, RIP, RNA stability assay and dual-luciferase reporter assay were applied to explore the underlying molecular mechanisms. The expression levels and prognostic role of YTHDF1/DDX21/HMGCS1 axis in CRC patients were analyzed by immunohistochemical staining and Kaplan-Meier plotter.

DDX21 enhanced CRC progression via promoting lipid metabolism. Mechanistically, YTHDF1 enhanced DDX21 mRNA stability by recognizing its m6A-modified sites. DDX21 further binded to 3‑hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) promoter region and directly activated HMGCS1 transcription. Moreover, our clinical data showed that a simultaneously high expression of YTHDF1, DDX21 and HMGCS1 predicted an unfavorable overall survival in CRC patients.

Our study demonstrates that the YTHDF1/DDX21/HMGCS1 axis promotes CRC progression via regulating lipid metabolism and DDX21 might be a promising target for CRC therapy.

Cancer incidence and mortality rates can vary widely among different racial and ethnic groups, attributed to a complex interplay of genetic, environmental and social factors. Recently, substantial progress has been made in investigating hereditary genetic risk factors and in characterizing tumour genomes. However, most research has been conducted in individuals of European ancestries and, increasingly, in individuals of Asian ancestries. The study of germline and somatic genetics in cancer across racial and ethnic groups using omics technologies offers opportunities to identify similarities and differences in both heritable traits and the molecular features of cancer genomes. An improved understanding of population-specific cancer genomics, as well as translation of those findings across populations, will help reduce cancer disparities and ensure that personalized medicine and public health approaches are equitable across racial and ethnic groups.

The very prevalent nature, genetic variability, and intricate tumor microenvironment (TUME) of colorectal cancer (COREC) are its defining features. In order to better understand the molecular and cellular make-up of COREC, this work used single-cell RNA sequencing (SRNAS) to isolate and characterize important cell types as well as their interactions within the TUME. Our analysis of 51,204 cells yielded six distinct types: epithelial, fibroblast, endothelial, T&NK, B, and myeloid. C3 B cells were shown to be the most active in immunological regulation, according to chemokine signaling study, which was one of seven clusters of B cells that were thoroughly subtyped. The examination of copy number variation (CONUV) revealed a great deal of genetic variability, especially in epithelial cells. We traced the activity of three key transcription factor clusters (M1, M2, and M3) across all B cell subtypes using transcription factor analysis. We created a predictive model that correctly sorts patients according to survival results by using marker genes from C3 B cells. In addition, the relationship between genetic changes and the immune system was better understood by tumor mutational burden (TUMUB) and immune infiltration studies. Our research sheds light on the genetic complexity and cellular variety of COREC, which in turn opens up new possibilities for targeted treatments and individualized approaches to patient care.

Optimal prognostic stratification for colorectal liver metastases (CRLM) patients undergoing surgery with neoadjuvant therapy (NAT) remains elusive. This study aimed to develop and validate dual-time-point radiomic models for CRLM prognosis prediction using pre- and post-NAT imaging features.

Radiomic features were extracted from four MRI sequences in 100 cases of CRLM patients who underwent NAT and radical resection. RAD scores were generated, and clinical/pathologic variables were incorporated into uni- and multivariate Cox regression analyses to construct prognosis models. Time-ROC, time-C index, decision curve analysis (DCA), and calibration curves assessed the predictive performance of Fong score and pre- and post-NAT models for overall survival (OS) and disease-free survival (DFS) in a testing set.

The final models included four variables for OS and three variables for DFS. The post-NAT models outperformed the pre-NAT models in time-ROC, time-C index, calibration, and DCA analysis, except for the 1-year DFS area under the curve (AUC). The Fong score models underperformed. The post-NAT OS RAD score effectively stratified patients into prognostic subgroups.

The radiomic models incorporating pre- and post-NAT MRI features and clinical/pathologic variables effectively stratified CRLM patients prognositically. The post-NAT models demonstrated superior performance.

Imaging biomarkers are emerging as non-invasive predictors of cancer prognosis and clinical outcome. We assessed tumor-specific ("radiomics") and body composition imaging features ("morphomics") extracted from baseline pre-treatment CT for prediction of recurrence in patients with stage III colorectal cancer (CRC).

Patients with newly diagnosed stage III CRC were enrolled in this prospective observational study. Patients with available preoperative scans were included (N = 101). The tumor, if visible, was manually segmented and first-order radiomics features were extracted with a commercially available software. The morphomics features (reflecting muscle, fat, and bone characteristics) were extracted in a standardized fashion using a proprietary software and the values were adjusted and normalized based on a reference standard. Time to recurrence was the final outcome. Correlation between demographics, clinical features, radiomics, and morphomics features and outcome were assessed using univariate and multivariate tests as well as Kaplan-Meier and log-rank tests.

Morphomic analysis was performed in all 101 patients. 60 patients had discrete tumors suitable for radiomics analysis. These patients had lower ECOG score (p < 0.05), more muscle mass (p > 0.05), and lower fat density (p > 0.05) compared to the patients in whom radiomics analysis could not be performed. Pathological stage (HR: 2.69; p = 0.03), CEA level after surgery (HR: 1.11 for 1 ng/mL; p < 0.005), bone mineral density (HR: 1.01 for 1 Hounsfield Unit; p < 0.01), and tumor skewness (HR: 0.33 for 1 unit; p < 0.05) had association with recurrence based on both univariate and multivariate analyses. A model using Cox's regression analyses was able to divide the patients into low-, medium-, and high-risk for recurrence.

Both radiomics and morphomics features were independently associated with the risk of CRC recurrence and, when combined, each contributed valuable information to explain risk of recurrence.

Clinical trial.gov NCT02842203. Patient recruitment occurred between 22/07/2016 and 18/03/2020.

Colon and rectum cancer (CRC) is a major health burden in China, with notable gender disparities. This study was designed to analyze trends in CRC incidence, prevalence, and mortality from 1990 to 2021 and to project future trends.

Using data from the Global Burden of Disease (GBD) Study 2021, we examined CRC burden in China, including incidence, prevalence, mortality, disability-adjusted life years (DALYs), years lived with disability (YLDs), and years of life lost (YLLs). Joinpoint regression, Bayesian age-period-cohort (BAPC) models, and age-period-cohort (APC) analysis identified trends and projected incidence up to 2030.

In 2021, CRC incidence was 658,321 cases, disproportionately affecting males, with an age-standardized incidence rate of 42.24 per 100,000 in males and 21.87 per 100,000 in females. The CRC-related deaths reached 275,129, with higher mortality in males (18.95 per 100,000) than females (9.34 per 100,000). The DALYs totaled 6,848,390 and largely impacted males. Joinpoint analysis showed a persistent increase in incidence and prevalence, especially in younger cohorts, whereas mortality declined slightly but began rising again after 2015. The BAPC analysis projected further incidence growth, particularly in males, through 2030. The APC analysis revealed higher CRC risk among younger cohorts, suggesting increasing early-onset CRC linked to lifestyle risk factors, such as smoking, high alcohol consumption, and diets low in fiber and calcium, with a stronger effect on males.

The increase of CRC incidence and prevalence in China, particularly among males, underscores the need for targeted prevention and early detection. Future research should address gender disparities and modifiable lifestyle risks through public health interventions.

Colorectal cancer (CRC) mortality hotspots in rural Washington, notably Yakima and Richland, identified an 8-year earlier median age of death in non-white patients. Post-pandemic data from WA State Department of Health and MultiCare's electronic health records revealed a 40 ​% decrease in CRC screenings.

During a 2023 CRC prevention summit, barriers and solutions were discussed focusing on rural Hispanic laborers as this population is often seen at partner locations, Yakima Valley Farm Workers Clinic (YVFWC).

Community outreach-Our team established a presence at Yakima's largest health fair, Fiesta de Salud. We also provided screening resources at Richland's farmers' markets. Planned events-- We will network with local community leaders and health providers to actualize screening (stool-based testing, hands-on endoscopy training).

Persistent CRC mortality disparities in Washington State underscores the need for targeted interventions. Partnering with organizations and engaging in community outreach aims to increase screening rates and enhance education.

Despite significant advancements in managing colorectal cancer (CRC), the issues of efficient diagnosis and targeted therapy remain demanding. To address these challenges and improve treatment outcomes while reducing the cost and side effects, there is a need for more effective theranostic systems that combine diagnostic techniques with therapeutic modalities. This study introduces a pioneering approach for the synthesis of a porous bio-MOF (biodegradable metal-organic framework) using iron as the metal component and curcumin as the pharmaceutical ingredient. Subsequently, the developed drug delivery system was equipped with the anticancer drug doxorubicin (DOX), coated with biocompatible polyethylene glycol (PEG), and targeted with a CRC-specific aptamer (EpCAM). The physicochemical characterization confirmed the successful synthesis of the bio-MOF, demonstrating high encapsulation efficiency and pH-dependent release of DOX. In vitro studies for anticancer activity, cellular uptake, and mechanism of cell death demonstrated that in the case of positive EpCAM HT-29 cells, Apt-PEG-MOF@DOX had enhanced internalization that resulted in massive apoptosis. In vivo studies of the nanoparticles were then conducted in immunocompromised C57BL/6 mice bearing HT-29 tumors. These studies showed that the targeted platform could induce efficient tumor regression with reduced systemic toxicity. The targeted bio-MOF also exhibited MRI imaging properties useful for monitoring tumors. Significantly, the biocompatibility of the introduced bio-MOF was enhanced by pursuing the green synthesis method, which does not engage toxic solvents and strong acids. Overall, this multimodal system acts diversely as a tumor imaging agent and a therapeutic delivery platform suitable for CRC theranostics.

Colorectal cancer (CRC) is the third most common cancer and remains a significant challenge due to high rates of drug resistance and limited therapeutic options. Circular RNAs (circRNAs) are increasingly recognized for their roles in CRC initiation, progression, and drug resistance. However, no circRNA-based therapies have yet entered clinical development, underscoring the need for comprehensive detection and mechanistic studies of circRNAs in CRC. Here, we identified and characterized a circular RNA, circ_0001766 (hsa_circ_0001766), through microarray analysis of CRC tissues. Our results showed that circ_0001766 is downregulated in CRC tissues and closely associated with patient survival and metastasis. Functional experiments demonstrated that circ_0001766 inhibits CRC cell proliferation, migration and invasion both in-vitro and in-vivo. Mechanistically, hypoxia downregulates Quaking (QKI), an RNA-binding protein essential for the biogenesis of circ_0001766 by binding to introns 1 and 3 of PDIA4 pre-mRNA. Reduced QKI expression under hypoxic conditions leads to decreased circ_0001766 levels in CRC. Circ_0001766 acts as a competitive endogenous RNA, sponging miR-1203 to prevent the degradation of PPP1R3C mRNA. Loss of circ_0001766 results in decreased PPP1R3C expression, leading to the activation of mTOR signaling and increased phosphorylation of Myc, which promotes CRC progression and rapamycin resistance. Our study reveals that overexpression of circ_0001766 or PPP1R3C in CRC cells inhibits the mTOR and Myc pathway, thereby resensitizing cells to rapamycin. The combination of circ_0001766 or PPP1R3C with rapamycin markedly inhibits CRC cell proliferation and induces apoptosis by reducing rapamycin-induced Myc phosphorylation. In summary, our study elucidates a critical circ_0001766/miR-1203/PPP1R3C axis that modulates CRC progression and rapamycin resistance. Our findings highlight circ_0001766 as a promising therapeutic target in CRC, providing a new avenue for enhancing the efficacy of existing treatments and overcoming drug resistance.

Despite advances in metastatic colorectal cancer (mCRC) treatment, long-term survival remains poor, particularly in right-sided colorectal cancer (RCRC), which has a worse prognosis compared to left-sided CRC (LCRC). This disparity is driven by the complex biological diversity of these malignancies. RCRC and LCRC differ not only in clinical presentation and outcomes but also in their underlying molecular and genetic profiles. This article offers a detailed literature review focusing on the distinctions between RCRC and LCRC. We explore key differences across embryology, anatomy, pathology, omics, and the tumor microenvironment (TME), providing insights into how these factors contribute to prognosis and therapeutic responses. Furthermore, we examine the therapeutic implications of these differences, considering whether the conventional classification of CRC into right- and left-sided forms should be refined. Recent molecular findings suggest that this binary classification may overlook critical biological complexities. Therefore, we propose that future approaches should integrate molecular insights to better guide personalized treatments, especially anti-EGFR therapies, and improve patient outcomes.

Lymph node ratio (LNR) and log odds of positive lymph nodes (LOODS) are considered to be potentially more rigorous metastatic lymph node stratification patterns than AJCC N stage due to the integration of the number of examined lymph nodes. Based on the data of colorectal cancer obtained from the Surveillance, Epidemiology, and End Result (SEER) database, comparison of the stratification performance between different prognostic models was validated by statistical methods, includingchi-square test, Cox regression analysis, Kaplan-Meier survival analysis, and Time-dependent Area Under Curve. A prognostic outcome-oriented statistical method based on Log-rank test was performed to determine the cutoff value of LNR. External validation cohort obtained from Zhejiang Cancer Hospital was used to validate the model performance and cutoff value. In the SEER database cohort, the optimal cutoff value for adequate or inadequate lymph node clearance was 14. In performance comparisons, LNR performance was superior to lymph node count alone and similar to LODDS. The optimal cutoff values for LNR were analyzed to be 0.11 (P < 0.001), 0.39 (P < 0.001) and 0.68 (P < 0.001), respectively. The stratification performance of modified N stage phased with the above cutoff value outperforms AJCC N stage. Kaplan-Meier survival analysis of the differences in patient distribution between the two staging systems also demonstrated the excellence of the LNR system. Above results were verified in the external verification cohort. The modified N stage based on LNR has better stratification performance than the AJCC N stage.

Upon metastatic seeding in the liver, liver macrophages, including Kupffer cells, acquire a transcriptional profile typical of tumor-associated macrophages (TAMs), which support tumor progression. MicroRNAs (miRNAs) fine-tune TAM pro-tumoral functions, making their modulation a promising strategy for macrophage reprogramming into an anti-tumoral phenotype. Here, we analyze the transcriptomic profiles of liver and splenic macrophages, identifying miR-342-3p as a key regulator of liver macrophage function. miR-342-3p is highly active in healthy liver macrophages but significantly downregulated in colorectal cancer liver metastases (CRLMs). Lentiviral vector-engineered liver macrophages enforcing miR-342-3p expression acquire a pro-inflammatory phenotype and reduce CRLM growth. We identify Slc7a11, a cysteine-glutamate antiporter linked to pro-tumoral activity, as a direct miR-342-3p target, which may be at least partially responsible for TAM phenotypic reprogramming. Our findings highlight the potential of in vivo miRNA modulation as a therapeutic strategy for TAM reprogramming, offering an approach to enhance cancer immunotherapy.

To evaluate how well the Node Reporting and Data System (Node-RADS) diagnoses lymph node involvement (LNI) in the initial stages of rectal cancer, utilizing contrast-enhanced CT (CE-CT), T2-weighted MRI (T2WI) and contrast-enhanced T1-weighted MRI (T1CE).

This retrospective study included 113 rectal cancer patients who underwent radical surgery without neoadjuvant therapy. Two radiologists independently assessed regional lymph nodes using the highest NODE-RADS classification and histopathology as reference criteria. Diagnostic performance was evaluated using receiver operating characteristic (ROC) curve analysis. Statistical analysis was performed using the McNemar test with Bonferroni correction for multiple comparisons.

Node-RADS showed improved diagnostic performance over short-axis diameter (SAD) in all modalities (AUC: 0.838 vs. 0.744 for CE-CT, 0.845 vs. 0.747 for T2WI, 0.853 vs. 0.786 for T1CE; all P < 0.05). The sensitivity and specificity of Node-RADS across three modalities ranged from 76.19 - 78.57% and 91.55 - 92.96%, respectively. Pairwise comparisons of sensitivity and specificity among the three modalities showed no significant differences after Bonferroni correction (all McNemar test P = 1.0). There was no significant difference in Node-RADS performance among the three modalities (all P > 0.05). The weighted kappa values were 0.742-0.798.

Node-RADS demonstrated superior diagnostic performance over SAD measurements and similar diagnostic effectiveness in assessing LNI for primary rectal cancer stages across CE-CT, T2WI, and T1CE.

Colorectal cancer (CRC) is a malignant epithelial tumor with high morbidity and mortality. In CRC treatment, irinotecan (CPT-11) as a chemotherapeutic drug is widely applied. However, its half-life is short, leading to large dosages and severe side effects. Red blood cells (RBCs) are biocompatible drug carriers with high capacity, avoiding premature drug degradation and achieving slow drug release. Nanoalumina (AN) is an emerging immune adjuvant that can enhance the immune response. Here, we used RBCs as carriers and absorbed AN to construct AN-CPT-11-RBCs. CPT-11 would induce tumor cell death, releasing much tumor antigen, while AN would activate immune cells to recognize newly released antigens and induce lymphocyte proliferation, enhancing the antitumor effect simultaneously. With loading amounts of 4 mg of CPT-11 and 3 mg of AN per 109 RBCs, AN-CPT-11-RBCs had similar properties to natural RBCs. In vivo, AN-CPT-11-RBCs could circulate for 9 days and stimulate the proliferation of lymphocytes in the spleen and tumor tissue, having a higher tumor growth inhibition rate of 74.01% and a lower frequency of administration. In conclusion, AN-CPT-11-RBCs attain the co-delivery of CPT-11 and AN for the synergistic treatment of CRC.

Replicon RNA (RepRNA) represents a cutting-edge technology in the field of vaccinology, fundamentally transforming vaccine design and development. This innovative approach facilitates the induction of robust immune responses against a range of infectious diseases and cancers. RepRNA vaccines leverage the inherent capabilities of RNA-dependent RNA polymerase associated with self-replicating repRNA, allowing for extreme replication within host cells. This process enhances antigen production and subsequently stimulates adaptive immunity. Additionally, the generation of double-stranded RNA during RNA replication can activate innate immune responses. Numerous studies have demonstrated that repRNA vaccines elicit potent humoral and cellular immune responses that are broader and more durable than those generated by conventional mRNA vaccines. These significant immune responses have been shown to provide protection in various models for infectious diseases and cancers. This article will explore the design and delivery of RepRNA vaccines, the mechanisms of immune activation, preclinical studies addressing infectious diseases and tumors, and related clinical trials that focus on safety and immunogenicity.

Colorectal cancer (CRC), as a high-incidence malignancy, continues to present significant challenges in prevention, screening, and treatment. Curcumin (Cur) exhibits notable anti-inflammatory and anticancer properties. Despite its poor solubility in water and low bioavailability, high concentrations of Cur are detected in the gastrointestinal tract after oral administration, suggesting that it may directly interact with the gut microbiota and exert regulatory effects. This study aims to explore the mechanisms by which Cur improves CRC by modulating gut microbiota. Firstly, we evaluated the effect of Cur on CRC cell viability in vitro using the MTT assay, and the results showed a significant inhibitory effect on CRC cell growth. The IC50 values for Cur in CT26 and RKO cells were 23.52 μM, 16.11 μM, and 13.62 μM at 24, 48, and 72 hours, respectively, and 26.3 μM, 16.52 μM, and 14.22 μM at 24, 48, and 72 hours, respectively. Cur induced apoptosis and caused G2 phase cell cycle arrest in tumor cells. Subsequently, we established a CRC mouse model. Oral administration of Cur at 15 mg kg-1 and 30 mg kg-1 inhibited CRC progression, as evidenced by reduced tumor volume, histological analysis, immunohistochemistry, and an increased number of CD8+ T cells infiltrating the tumors. Ferroptosis in tumor cells was also observed. Cur partially restored the gut microbiota of CRC mice, altering the abundance and diversity of the gut microbiota and affecting serum metabolite distribution, with significant increases in the abundance of SCFA-producing microbes such as Lactobacillus and Kineothrix. To verify causality, we designed a fecal microbiota transplantation (FMT) experiment. Compared with CRC mice, the fecal microbiota from Cur-treated mice significantly alleviated CRC symptoms, including slowed tumor growth, enhanced CD8+ T cell tumor infiltration, and induced ferroptosis in tumor cells. Additionally, when gut microbiota was depleted with antibiotics, Cur's antitumor effects disappeared, suggesting that Cur mitigates CRC in a gut microbiota-dependent manner. These findings provide new insights into the mechanisms underlying CRC and propose novel therapeutic interventions, emphasizing the interaction between gut microbiota and immune responses within the tumor immune microenvironment (TIME).

Colorectal cancer (CRC), as a highly prevalent malignant tumor globally, faces the dual challenges of drug resistance of cancer stem cells and immune escape in its treatment. Although the traditional Chinese medicine Yigong San (YGS) shows potential in improving the clinical adverse reactions of CRC, its core active components and mechanism of action remain unclear. Based on network pharmacology screening, this study for the first time discovered that Gomisin B might regulate the progression of CRC through the Toll-like receptor 4/Nuclear Factor-kappa B (TLR4/NF-κB) signaling pathway, and aimed to systematically reveal the molecular mechanisms by which YGS and Gomisin B inhibited the malignant phenotypes and immune escape of CRC cells.

The The Cancer Genome Atlas (TCGA) database was integrated with network pharmacology analysis to screen for the key target of CRC, Gomisin B, and its associated TLR4/NF-κB pathway. Through in vitro CRC stem cell models and mouse xenograft tumor models, techniques such as CCK-8, Transwell, flow cytometry, qPCR/WB were used to evaluate the effects of YGS and Gomisin B on proliferation, migration, invasion, apoptosis, and epithelial-mesenchymal transition (EMT), and to detect the expression of TLR4 and downstream inflammatory factors.

Both YGS and Gomisin B inhibited the proliferation, migration and invasion of CRC stem cells and tumor tissues. Meanwhile, they promoted apoptosis but reduced the expression of the inflammatory factor TLR4 and proteins associated with the NF-κB pathway, thereby exerting suppressive effects on tumorigenesis and disease progression. YGS might also impede EMT progression through modulation of the NF-κB pathway.

This study for the first time elucidated the dual anti-tumor mechanisms of YGS, which sensitized CRC stem cells and inhibited immune escape by targeting the TLR4/NF-κB pathway through Gomisin B. It provides a pharmacological basis for the modern research of traditional Chinese medicine compound against CRC.

Not applicable.

Metastatic BRAFV600E colorectal cancer (CRC) confers poor prognosis and represents a therapeutic bottleneck. To identify resistance mechanisms of the mitogen-activated protein kinase (MAPK) pathway in BRAFV600E CRC, we perform genome-wide CRISPR-Cas9 screening and discover that targeting glutathione peroxidase 4 (GPX4) overcomes resistance to BRAF inhibitor (BRAFi) combined with or without epidermal growth factor receptor inhibitor (EGFRi) in BRAFV600E CRC. Specifically, BRAFi ± EGFRi upregulates GPX4 expression, which antagonizes therapy-induced ferroptosis. Moreover, polo-like kinase 1 (PLK1) substrate activation promotes PLK1 translocation to the nucleus, activating chromobox protein homolog 8 (CBX8) phosphorylation at Ser265 to drives GPX4 expression. Targeting PLK1 enhances BRAFi ± EGFRi inhibition and triggers ferroptosis in vitro, vivo, organoid, and patient-derived xenograft model. Collectively, we demonstrate a PLK1-CBX8-GPX4 signaling axis that relays the ferroptosis mechanism of therapeutic resistance and propose a clinically actionable strategy to overcome BRAFi ± EGFRi resistance in BRAFV600E CRC.

Despite the worrisome rise of early-onset colorectal cancer (EOCRC), risk factors have not been definitively established. We use a large, granular database to evaluate risk factors for EOCRC, investigate differences in associations with EOCRC and later-onset CRC (LOCRC), and compare metrics of accelerated aging, a hypothesized driver of EOCRC.

This was a case-control analysis within the UK Biobank. Risk factors for each cancer were identified and compared, including aging measures (chronological age, telomere length, PhenoAge, and homeostatic dysregulation).

A total of 31,164 persons were matched. We found an increased risk of EOCRC with PRS (OR 1.53; 95% CI 1.19-1.97; p < 0.001). LOCRC was associated with increasing PRS (OR 1.48; 95% CI 1.44 - 1.53; p < 0.001), increasing waist-to-hip ratio (OR 5.81; 95% CI 3.25 - 10.38; p < 0.001), family history of CRC (OR 1.27; 95% CI 1.16 - 1.40; p < 0.001), and history of smoking (OR 1.11; 95% CI 1.03 - 1.19; p = 0.01). Male sex and prior CRC screening were associated with reduced risk of LOCRC. The inclusion of PhenoAge as the measure of aging demonstrated the best model fit for both EOCRC and LOCRC. For each year that PhenoAge exceeded chronological age, the odds of EOCRC increased by 7%, while odds of LOCRC only increased by 1%.

Within this study, we find that genetic risk variants are a significant driver of EOCRC risk. Accelerated aging appears to be associated with increased risk of both EOCRC and LOCRC, and measures such as PhenoAge warrant continued study.

Most persons with colorectal cancer (CRC) carry adenomatous polyposis coli (APC) truncation leading to aberrant Wnt-β-catenin signaling; however, effective targeted therapy for them is lacking as the mechanism by which APC truncation drives CRC remains elusive. Here, we report that the cholesterol level in the inner leaflet of the plasma membrane (IPM) is elevated in all tested APC-truncated CRC cells, driving Wnt-independent formation of Wnt signalosomes through Dishevelled (Dvl)-cholesterol interaction. Cholesterol-Dvl interaction inhibitors potently blocked β-catenin signaling in APC-truncated CRC cells and suppressed their viability. Because of low IPM cholesterol level and low Dvl expression and dependence, normal cells including primary colon epithelial cells were not sensitive to these inhibitors. In vivo testing with a xenograft mouse model showed that our inhibitors effectively suppressed truncated APC-driven tumors without causing intestinal toxicity. Collectively, these results suggest that the most common type of CRC could be effectively and safely treated by blocking the cholesterol-Dvl-β-catenin signaling axis.

Colorectal cancer (CRC) is a leading factor in cancer mortality globally. Ferroptosis, a regulated cell death described via lipid peroxidation, is crucial in cancer biology. This study explores the link between ferroptosis, FADS2, and CRC, focusing on the prognostic significance and therapeutic potential of targeting FADS2.

The differential expression analysis of the Cancer Genome Atlas-colon adenocarcinoma (TCGA-COAD) and GSE36400 datasets was conducted to determine key ferroptosis-related genes, followed by functional enrichment analysis. Prognosis-related genes were assessed utilizing Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression. Genetic variation analysis and immune analysis were employed to evaluate the clinical significance of FADS2. The impacts of FADS2 knockdown on CRC cell migration, proliferation, invasion, and ferroptosis were evaluated by in vitro cell experiments.

64 key ferroptosis-related genes in CRC were highly enriched in pathways such as glutathione metabolism and peroxisome. Eleven prognosis-associated genes were identified, with TP53 showing the highest mutation frequency. High FADS2 expression was linked to poorer prognosis and higher immune cell infiltration. FADS2 knockdown significantly decreased glutathione (GSH) levels, SLC7A11, and GPX4 expression, increased malondialdehyde (MDA) levels, indicating the promotion of ferroptosis. Functional tests revealed knockdown FADS2 repressed CRC cell proliferation, migration, and invasion. SLC7A11 or GPX4 overexpression partially rescued the effects of FADS2 knockdown. Additionally, FADS2 knockdown enhances the chemosensitivity of CRC cells to oxaliplatin.

FADS2 is essential for encouraging CRC cell proliferation and tumor growth by preventing ferroptosis. Targeting FADS2 may enhance ferroptosis and suppress CRC progression, offering a possible course of treatment for CRC patients. The knockdown of FADS2 enhances the chemosensitivity of CRC cells to oxaliplatin, providing valuable insights for future clinical applications.