Colorectal Cancer Research Articles

Case report: a rare case of hereditary colorectal cancer and brain tumor with café au lait spots in a child: constitutional mismatch repair deficiency (CMMRD) syndrome

Abstract Background Colorectal carcinoma (CRC) is rarely seen in the pediatric population. Hereditary cancers due to mismatch repair deficiency cause colorectal, brain, hematological malignancies, and other tumors in early childhood. Case presentation We present an 11-year-old boy who presented with colorectal cancer and brain tumor due to constitutional mismatch repair deficiency syndrome with a family history of sibling deaths due to brain tumors. Conclusions Hereditary cancers arising due to mismatch repair gene mutations cause early colorectal and brain cancers in children. The members of such families should be genetically screened for any mutations.

Impact of Sensitive Circulating Tumor DNA Monitoring on CT Scan Intervals During Postoperative Colorectal Cancer Surveillance

Objective: This study investigated whether digital polymerase chain reaction (dPCR)-based circulating tumor DNA (ctDNA) monitoring can allow longer intervals between computed tomography (CT) scans during postoperative surveillance of colorectal cancer (CRC). Background: Practical guidelines still recommend intensive postoperative surveillance of CRC using periodical CT scans and serum carcinoembryonic antigen testing. Methods: The longitudinal dynamics of ctDNA for 52 patients with CRC as measured by dPCR using probes targeting 87 individual tumor-specific mutations (1–5 per patient) were compared with results from conventional (ie, clinical) surveillance using serum tumor markers and CT. Results: A total of 382 CT procedures were carried out for the patient cohort (3.3/year per patient) and the median lead time from ctDNA relapse to clinical relapse was 182 days (range, 0–376 days). If the CT interval was annual, potential delays in the detection of clinical relapse would have occurred for 7 of the 10 patients who experienced clinical relapse (9 of 13 events), with a median delay of 164 days (range, 0–267 days). If annual CT surveillance was performed together with ctDNA monitoring, 218 (57.1%) CTs would not have been needed to detect the first clinical relapse. In addition, the ctDNA monitoring would have provided a lead time of 339 days for detection of clinical relapse (range, 42–533 days). Conclusions: Our findings suggest that the ctDNA monitoring as part of postoperative surveillance and clinical relapse detection for patients with CRC could allow the CT interval to be lengthened. Trial Registration: This trial was registered with University Hospital Medical Information Network Clinical Trial Registry (UMIN000045114).

Sex differences in the impact of multimorbidity on long-term mortality for patients with colorectal cancer: a population registry-based cohort study.

Women have better survival than men patients with colorectal cancer (CRC), but the extent to which this is due to multimorbidity is unclear. A population-based study of 1843 patients diagnosed with CRC in Australia. Data included patient's demographics, multimorbidity, tumour histology, cancer stage, and treatment. We estimated the risks of all-cause mortality and cause-specific mortality due to cancer or non-cancer causes. Men had lower survival than women (P≤0.010) amongst those diagnosed at Stages I-III (15-year survival: 56.0% vs 68.0%, 48.5% vs 60.7%, 34.8% vs 47.5%, respectively), excepting Stage IV (14.4% vs 12.6%; P=0.18). Married men exhibit better survival than those who were never married (P=0.006). Heart attacks (9.9% vs 4.3%, P<0.001) and emphysema (4.8% vs 2.1%, P=0.004) were more prevalent in men than women. Comorbid stroke and high cholesterol (adjusted hazard ratio, AHR=2.22, 95% confidence interval, CI=1.17-4.21, P=0.014) and leukaemia (AHR=6.36, 95% CI=3.08-13.1, P<0.001) increased the risk of cancer death for men only. For women, diabetes increased the risk of all-cause death (AHR=1.38, 95% CI=1.02-1.86, P=0.039) and high blood pressure increased the risk of death due to non-cancer causes (AHR=2.00, 95% CI=1.36-2.94, P<0.001). Separate models of CRC care are needed for men and women with consideration of multimorbidity and social factors.

Tailoring Tumor Cell Golgi Apparatus‐Targeting Self‐Assembled Peptide for Effective Immunotherapy via Reshaping MIF‐Mediated Immunosuppressive Network

AbstractThe immunosuppressive network formed by the enhanced crosstalk between tumor cells and various types of immune cells may ultimately lead to the formation of tumor immunosuppressive microenvironment (TIME). The Golgi apparatus (GA) of tumor cells is a key organelle in the formation of a tumor immunosuppressive network. However, there are no studies to show whether interfering with the GA of tumor cells can reshape the immunosuppressive network to enhance the effectiveness of immunotherapy. Therefore, the tumor cell GA‐targeting self‐assembled peptide (NF‐1) is tailored, and confirmed that NF‐1 treatment can achieve an effective immunotherapy and found that tumor cell‐derived GA‐dependent migration inhibitory factor (MIF) mediates the formation of immunosuppressive network in breast cancer (BRCA) through multi‐omics analysis, in vivo, and in vitro experiments. NF‐1 treatment‐induced MIF reduction can reshape the immunosuppressive network and convert a “cold” tumor into a “hot” tumor, thus enabling immunotherapy in BRCA and enhancing the ICB efficacy in colon adenocarcinoma (COAD). This study presents a general strategy for interfering with tumor GA for effective immunotherapy in BRCA, COAD, and other cancers characterized by a “cold” immune microenvironment.

BRAF mutant appendiceal adenocarcinoma differs from colorectal cancer but responds to BRAF-targeted therapy

BRAF mutant appendiceal adenocarcinoma differs from colorectal cancer but responds to BRAF-targeted therapy

The prognostic value of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in colorectal cancer and colorectal anastomotic leakage patients: a retrospective study

The prognostic value of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in colorectal cancer and colorectal anastomotic leakage patients: a retrospective study

Low-Density Lipoprotein (LDL) is Associated with Earlier Progression in Synchronous Metastatic Colorectal Cancer Treated without Curative Intent.

Low-density lipoprotein cholesterol (LDL) is associated with the occurrence of colorectal cancer (CRC). This study aims to investigate its prognostic role and associated clinicopathological factors in the metastatic setting. Patients with newly diagnosed synchronous metastatic CRC were included. Patients were grouped according to the serum LDL levels at the diagnosis (≤ 130mg/dL: Normal-LDL, > 130mg/dL: High-LDL). LDL-associated clinicopathological factors, progression-free survival (PFS), and overall survival (OS) were assessed. A total of 90 patients were included. 44.4% (n = 40) was in the normal-LDL and 56.6% (n = 50) in the high-LDL group. Colonic localization of the primary tumor was more frequent in the high-LDL group (90% vs. 67.5%, p = 0.009). The high-LDL group more frequently had local treatments [metastasectomy (26% vs. 2.5%, p = 0.002) and embolization-ablation (38% vs. 17.5%, p = 0.033)]. Despite higher curative intent with local treatments in the high-LDL group, PFS [10.03months (95% Confidence Interval (CI):6.97-14.77) vs 9.63 mo. (95% CI: 7.93-14.00), p = 0.872] and OS [20.87 mo. (95% CI: 14.87-36.47) vs. 17.63 mo. (95% CI: 14.30-43.03), p = 0.925] did not differ from the normal-LDL. Among patients treated without any curative intent, high LDL was associated with significantly worse PFS [4.97 mo. (95% CI: 3.00-7.73) vs. 8.43 mo. (95% CI: 6.10-9.90), p = 0.048]. This study suggests that serum LDL is associated with colonic primary localization in synchronous metastatic CRC. Levels > 130mg/dL at diagnosis may be associated with worse survival and may be further investigated as a biomarker. Larger, multicenter and prospective studies are needed.

Right-Sided Versus Left-Sided Colon Cancer—A 5-Year Single-Center Observational Study

Background: Global colorectal cancer (CRC) incidence is significant, constituting 15% of all cancer cases with 1.4 million new diagnoses annually. Recent research suggests categorizing CRC into three clinical groups: right colon cancer (RCC), left colon cancer (LCC), and rectal cancer, each with distinct embryological and molecular characteristics. Methods: A retrospective analysis of 189 patients (103 men, 86 women) undergoing surgery for RCC and LCC from January 2018 to December 2023 was performed. Results: LCC was a more common localization (98, 51.85%) than RCC (91, 48.15%). Patients with RCC were older than patients with LCC (70 (36–92, IQR 11) vs. 68 (38–84, IQR 12.5) years; p = 0.02). The duration of surgical procedure was comparable in both groups (225 (120–420, IQR 80) vs. 210 (105–505, IQR 85) minutes; p = 0.16). Complications occurred in 16 (17.58%) patients with RCC and in 15 (15.31%) patients with LCC (p = 0.72). One-year overall survival was 92.76% (SE 2.16%) (91.57% (SE 3.43%) in the RCC group and 93.99% (SE 2.61%) in the LCC group; p = 0.79). Conclusions: Colon cancer incidence is increasing globally due to economic and lifestyle factors. Our study reflects this trend, noting a rise in cases from 2018 to 2023. Despite several differences, overall survival rates do not significantly differ between RCC and LCC patients. Understanding clinical disparities is crucial for optimizing patient outcomes.

S-Adenosylmethionine: A Multifaceted Regulator in Cancer Pathogenesis and Therapy

S-adenosylmethionine (SAMe) is a key methyl donor that plays a critical role in a variety of cellular processes, such as DNA, RNA and protein methylation, essential for maintaining genomic stability, regulating gene expression and maintaining cellular homeostasis. The involvement of SAMe in cancer pathogenesis is multifaceted, as through its multiple cellular functions, it can influence tumor initiation, progression and therapeutic resistance. In addition, the connection of SAMe with polyamine synthesis and oxidative stress management further underscores its importance in cancer biology. Recent studies have highlighted the potential of SAMe as a biomarker for cancer diagnosis and prognosis. Furthermore, the therapeutic implications of SAMe are promising, with evidence suggesting that SAMe supplementation or modulation could improve the efficacy of existing cancer treatments by restoring proper methylation patterns and mitigating oxidative damage and protect against damage induced by chemotherapeutic drugs. Moreover, targeting methionine cycle enzymes to both regulate SAMe availability and SAMe-independent regulatory effects, particularly in methionine-dependent cancers such as colorectal and lung cancer, presents a promising therapeutic approach. Additionally, exploring epitranscriptomic regulations, such as m6A modifications, and their interaction with non-coding RNAs could enhance our understanding of tumor progression and resistance mechanisms. Precision medicine approaches integrating patient subtyping and combination therapies with chemotherapeutics, such as decitabine or doxorubicin, together with SAMe, can enhance chemosensitivity and modulate epigenomics, showing promising results that may improve treatment outcomes. This review comprehensively examines the various roles of SAMe in cancer pathogenesis, its potential as a diagnostic and prognostic marker, and its emerging therapeutic applications. While SAMe modulation holds significant promise, challenges such as bioavailability, patient stratification and context-dependent effects must be addressed before clinical implementation. In addition, better validation of the obtained results into specific cancer animal models would also help to bridge the gap between research and clinical practice.

Enhanced anticancer efficacy of aluminum-curcumin complex compared to curcumin in colorectal cancer cells.

The evaluation of anti cancer treatments involves various methods, one of which is the use of biomarkers for therapeutic strategy. This study aimed to compare the anticancer effects of Aluminum curcumin (ACC) with curcumin (CC) in human CRC cells. In this study, the cells were classified into four groups: Group A as control cells, Group B included untreated CRC cells, and Groups C and D comprised cancer cells treated with CC and ACC, respectively. After determining the IC50 values for the drugs using the MTT assay, gene expression was analyzed through RT-PCR. The results of the study showed in group D, there was a more significant decrease in the expression of anti-apoptotic genes, including telomerase (0.67 ± 0.438), Bcl-2 (0.34 ± 0.077), and miRNA-21 (0.51 ± 0.056), compared to group C, where the expression levels were higher for the same genes: telomerase (1.5 ± 0.134), Bcl-2 (1.31 ± 0.014), and miRNA-21 (1.32 ± 0.085). Additionally, group D exhibited a more significant increase in the expression of pro-apoptotic genes, including BAX (3.15 ± 0.813), miRNA-122 (2.61 ± 0.056), and FASLG (1.89 ± 0.014), compared to group C, where the gene expression levels were lower: BAX (0.86 ± 0.106), miRNA-122 (1.01 ± 0.276), and FASLG (0.98 ± 0.099). Significant differences were observed between the majority of groups (P < 0.05). Furthermore, a higher number of apoptotic regions were observed in group D compared to group C. ACC as a new compound demonstrates enhanced anti-cancer potential compared to curcumin alone, due to the aluminum component's ability to stimulate the immune system. This synergy offers a promising therapeutic strategy for cancer treatment, with greater efficacy in targeting and eliminating cancer cells.

Cost-effectiveness of blood-based colorectal cancer screening – a simulation model incorporating real-world longitudinal adherence

ABSTRACT Objectives Although U.S. Preventive Services Task Force (USPSTF) recommended CRC screenings are effective; patient reluctance reduces adherence. Most cost-effectiveness models assume perfect adherence, yet one-third of eligible individuals aren’t current with CRC screening. Our study assesses the cost-effectiveness of Shield, an FDA-approved blood-based CRC screening test, using real-world adherence. Methods The CAN-SCREEN (Colorectal cANcer SCReening Economics and adherENce) model, a validated discrete-event simulation, evaluated clinical and economic outcomes of CRC screening under real-world adherence scenarios. We compared the Shield blood-based test administered every 3 years to no screening, considering it cost-effective if the incremental cost-effectiveness ratio (ICER) was under $100,000 per quality-adjusted life-year (QALY) gained. Results Shield increased QALYs by 154 and raised costs by $7.5 million per 1,000 individuals, with an ICER of $48,662 per QALY, meeting the $100,000/QALY threshold. Shield remained cost-effective up to a unit cost of $3,241 (at $100,000/QALY) and $4,942 (at $150,000/QALY). Sensitivity analyses confirmed cost-effectiveness with lower adherence to diagnostic colonoscopy (56.1%) and annual screenings. Conclusion The CAN-SCREEN model shows that Shield is cost-effective compared to no screening. Including real-world adherence improves accuracy in assessing screening strategies. Shield’s noninvasive approach offers a promising, cost-effective way to increase adherence and reduce CRC mortality.

Lymph node yield does not affect the cancer-specific survival of patients with T1 colorectal cancer: a population-based retrospective study of the U.S. database and a Chinese registry

Lymph node yield does not affect the cancer-specific survival of patients with T1 colorectal cancer: a population-based retrospective study of the U.S. database and a Chinese registry

Validated Integration of Tumor Deposits in N Staging for Prognostication in Colon Cancer.

Tumor deposits have prognostic value in colon cancer, but the current American Joint Committee on Cancer (AJCC) staging only considers them if there are no concurrent positive lymph nodes. To devise a staging system for colon cancer by integrating counts of tumor deposits with positive lymph nodes while retaining the current AJCC staging framework. This retrospective cohort study examines data from a large-volume, tertiary care center database (January 2010 through March 2023 with follow-up until December 2023) and the population-based National Cancer Database (January 2010 through December 2020 with follow-up until December 2021). Participants were adults (age 18-75 years) with stage III colon adenocarcinoma who underwent chemotherapy, and had a specified positive lymph node count and tumor deposit count were selected. A real positive lymph nodes count was developed and used to derive Sassun-Mayo N/tumor, lymph node, and metastasis (TNM) stages that were compared with the AJCC N/TNM stages. Receiver operating characteristic (ROC) curves and Kaplan-Meier analyses for 3-year overall survival were performed to assess the efficiency of the 2 staging systems. The concordance index was used for validation using the National Cancer Database. From a total patient number of 11 162 (institutional) and 848 704 (national), the final patient numbers were 788 and 77 790, respectively. The institutional database patients had a mean (SD) age of 58.5 (11.5) years; there were 433 male patients (54.9%) and 355 female (45.1%). The national database patients had a mean (SD) age of 59.3 (10.6) years; there were 40 315 male patients (51.8%) and 37 475 female (48.2%). ROC curve areas were improved using the Sassun-Mayo stages (3-year death for AJCC TMN, 0.63 [95% CI, 0.57-0.69] vs 0.66 [95% CI, for 0.60-0.72] for Sassun-Mayo TNM). Kaplan-Meier curves revealed visible overlaps among AJCC N stages, which were absent in the Sassun-Mayo N stages. The concordance index in the Sassun-Mayo N/TNM stages was 0.611 and 0.616, respectively, while in the AJCC N/TNM stages, it was 0.598 and 0.606, respectively. Patients upstaged from N1 to N2 (n = 10 307; 13.2%) had a 3-year overall survival rate nearly identical to that of AJCC N2a patients. Additionally, 3001 patients (3.9%) were upstaged from N2a to N2b, indicating that 13 308 patients (17.1%) with stage III colon cancer across cohorts were understaged. This study found that Sassun-Mayo N/TNM staging provided superior overall survival stratification compared with the current AJCC staging, suggesting that their implementation could improve prognostication in colon cancer.

The lactate receptor HCAR1 drives the recruitment of immunosuppressive PMN-MDSCs in colorectal cancer.

Most patients with colorectal cancer do not achieve durable clinical benefits from immunotherapy, underscoring the existence of alternative immunosuppressive mechanisms. Here we found that activation of the lactate receptor HCAR1 signaling pathway induced the expression of chemokines CCL2 and CCL7 in colorectal tumor cells, leading to the recruitment of immunosuppressive CCR2+ polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) to the tumor microenvironment. Ablation of Hcar1 in mice with colorectal tumors significantly decreased the abundance of tumor-infiltrating CCR2+ PMN-MDSCs, enhanced the activation of CD8+ T cells and, consequently, reduced tumor burden. We detected immunosuppressive CCR2+ PMN-MDSCs in tumor specimens from individuals with colorectal and other cancers. The US Food and Drug Administration-approved drug reserpine suppressed lactate-mediated HCAR1 activation, impaired the recruitment of CCR2+ PMN-MDSCs, boosted CD8+ T cell-dependent antitumor immunity and sensitized immunotherapy-resistant tumors to programmed cell death protein 1 antibody therapy in mice with colorectal tumors. Altogether, we described HCAR1-driven recruitment of CCR2+ PMN-MDSCs as a mechanism of immunosuppression.

EGFR inhibition augments the therapeutic efficacy of the NAT10 inhibitor Remodelin in Colorectal cancer.

Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide, and treatment options for advanced CRC are limited. The regulatory mechanisms of aberrant NAT10-mediated N4-acetylcytidine (ac4C) modifications in cancer progression remains poorly understood. Consequently, an integrated transcriptomic analysis is necessary to fully elucidate the role of NAT10-mediated ac4C modifications in CRC progression. NAT10 expression levels were analyzed in CRC samples and compared with those in corresponding normal tissues. The potential mechanisms of NAT10 in CRC were investigated using RNA sequencing, RNA immunoprecipitation sequencing, and acetylated RNA immunoprecipitation sequencing. Additional in vivo and in vitro experiments, including CCK-8 assays, colony formation and mouse xenograft models, were conducted to explore the biological role of NAT10-mediated ac4C modifications. We also evaluated and optimized a potential treatment strategy targeting NAT10. We found that NAT10 is highly expressed in CRC samples and plays a pro-oncogenic role. NAT10 knockdown led to PI3K-AKT pathway inactivation, thereby inhibiting CRC progression. However, treatment with the NAT10 inhibitor Remodelin induced only a limited and reversible growth arrest in CRC cells. Further epigenetic and transcriptomic analysis revealed that NAT10 enhances the stability of ERRFI1 mRNA by binding to its coding sequence region in an ac4C-dependent manner. NAT10 knockdown decreased ERRFI1 expression, which subsequently activated the EGFR pathway and counteracted the inhibitory effects on CRC. Based on these findings, we demonstrated that dual inhibition of NAT10 and EGFR using Remodelin and the EGFR-specific monoclonal antibody cetuximab resulted in improved therapeutic efficacy compared to either drug alone. Moreover, we observed that 5-Fluorouracil promoted the interaction between NAT10 and UBR5, which increased the ubiquitin-mediated degradation of NAT10, leading to ERRFI1 downregulation and EGFR reactivation. Triple therapy with Remodelin, cetuximab, and 5-Fluorouracil enhanced tumor regression in xenograft mouse models of CRC with wild-type KRAS, NRAS and BRAF. Our study elucidated the mechanism underlying 5-Fu-induced NAT10 downregulation, revealing that NAT10 inhibition destabilizes ERRFI1 mRNA through ac4C modifications, subsequently resulting in EGFR reactivation. A triple therapy regimen of Remodelin, cetuximab, and 5-Fu showed potential as a treatment strategy for CRC with wild-type KRAS, NRAS and BRAF.

Circular RNA microarray expression profile and potential function of circDOCK1 in colorectal cancer

IntroductionEndoscopic tissue biopsy combined with histopathology is the gold standard for the diagnosis of colorectal cancer (CRC); however, the invasive nature of this procedure hinders its acceptance by patients. Therefore, there exists a critical need to identify novel markers facilitating early CRC detection and prognosis. Circular RNAs (circRNAs) hold promise as novel clinical diagnostic markers. This study aimed to investigate the impact of circDOCK1 on CRC metastasis and prognosis as well as its underlying molecular mechanisms.MethodsWe explored circRNA expression profiles in four pairs of CRC tissues and adjacent non-carcinoma tissues via microarray analysis. After Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and circRNA–miRNA network analyses, circDOCK1 was chosen for further investigation. We evaluated its clinical relevance in 80 CRC tissue pairs and adjacent controls, correlating circDOCK1 expression with clinical characteristics. Follow-up data from patient telephone interviews were analyzed for survival outcomes. Transfection efficiency was confirmed via qRT-PCR in HCT116 and SW480 colon cells, and the effects of circDOCK1 on cell proliferation, migration, and invasion were assessed.ResultsMicroarray data revealed 149 significantly differentially expressed circRNAs, including 71 upregulated and 78 downregulated circRNAs, in CRC tissues. CircDOCK1 exhibited elevated expression in patients with CRC and emerged as an independent prognostic factor. Kaplan–Meier curve analysis suggested that circDOCK1 expression is an unfavorable prognostic factor in patients with CRC. In vivo experiments revealed that circDOCK1 overexpression enhanced the proliferation, migration, and invasion of CRC cells, with consistent results upon circDOCK1 downregulation.ConclusionThese data indicate that circDOCK1 may play a role in promoting the proliferation, migration, and invasion of CRC cells, suggesting its potential as a CRC biomarker.

Non-Conventional Dysplasia in Patients with Inflammatory Bowel Disease and Colorectal Adenocarcinoma: A Case-Cohort Study.

Patients with inflammatory bowel disease (IBD) face increased risk of colorectal cancer (CRC). While the natural history of conventional dysplastic precursor lesions has been well-studied, the neoplastic potential of recently described non-conventional (NC) IBD-associated colonic mucosal lesions is unclear. We aimed to assess the incidence of antecedent NC lesions in patients with IBD who developed CRC. A case-cohort study was performed to include patients with a diagnosis of IBD with or without CRC who underwent at least two surveillance endoscopic procedures at our institution between 1/1/2007 and 5/31/2023. NC lesions included serrated change and indefinite for dysplasia. Detection rates pre- and post-introduction of high definition (HD) surveillance colonoscopy were compared. In total, 87 patients with IBD and CRC and 200 patients with IBD without CRC were identified. Of the cases, a majority had ulcerative colitis (n=52, 60%), most commonly with extensive involvement (n=46, 89%). Conventional (HR 2.18, 95% CI 1.34-3.52) and NC (HR 2.28, 95% CI 1.59-3.26) lesions were associated with increased risk of CRC. Conventional lesions in the post-HD era appeared to have a stronger association with CRC (HR 2.79, 95% CI 1.62-4.77) than NC lesions (HR 1.62, 95% CI 0.86-3.06). Both conventional and NC lesions seem to be associated with increased risk of CRC. Conventional lesions are more strongly associated with CRC than NC lesions in the post-HD era, but misclassifications in the pre-HD era may have resulted in a biased increased risk estimate for NC lesions.

The impact of SEC23A on 5-FU chemotherapy sensitivity and its involvement in endoplasmic reticulum stress-induced apoptosis in colorectal cancer.

Colorectal cancer (CRC) represents a significant global health burden, with chemotherapy resistance representing a significant challenge to effective treatment. SEC23A, a core component of the COPII vesicle trafficking system, is of critical importance with regard to protein transport and cellular homeostasis. Nevertheless, its function in CRC progression and chemoresistance remains uncertain. The present study investigates the correlation between SEC23A expression and sensitivity to 5-fluorouracil (5-FU), a widely used chemotherapeutic agent, with particular emphasis on ER stress-induced apoptosis. A bioinformatic analysis was conducted to evaluate SEC23A expression in CRC and its association with patient prognosis. Chemotherapy sensitivity was predicted using GDSC data and validated experimentally using CRC cell lines with manipulated SEC23A expression. In order to explore the role of SEC23A in acquired drug resistance, patient-derived xenograft (PDX) models and 5-FU-resistant cell lines were employed. Apoptosis assays, cell cycle analysis, and ER stress modulation experiments were performed to elucidate the underlying mechanisms. SEC23A expression was significantly reduced in CRC samples compared to normal tissues. This reduction was linked to a poorer prognosis, including both overall and disease-specific survival. A correlation was observed between low SEC23A expression and increased resistance to 5-FU, as evidenced by both bioinformatic predictions and in vitro experiments. In PDX models, metastatic lesions exhibited decreased SEC23A expression following 5-FU treatment in comparison to primary tumors. Overexpression of SEC23A in 5-FU-resistant cell lines restored sensitivity to the drug and increased apoptosis. Bioinformatic and experimental analyses revealed a robust correlation between SEC23A and ER stress-related apoptotic pathways. Elevated expression of SEC23A was observed to facilitate the accumulation of misfolded proteins in response to 5-FU treatment, which in turn resulted in increased ER stress and apoptosis. SEC23A plays a crucial role in modulating the sensitivity of CRC cells to 5-FU by regulating ER stress-induced apoptosis. Its downregulation contributes to chemoresistance, indicating that SEC23A may serve as a prognostic marker and therapeutic target in CRC. Strategies aimed at upregulating SEC23A or enhancing ER stress may provide new avenues for overcoming chemoresistance and improving treatment outcomes for CRC patients.

Production of novel theranostic nano-vector based on superparamagnetic iron oxide nanoparticles/miR-497 targeting colorectal cancer.

Colorectal cancer (CRC) is a serious public health concern worldwide. Immune checkpoint inhibition medication is likely to remain a crucial part of CRC clinical management. This study aims to create new super paramagnetic iron oxide nano-carrier (SPION) that can effectively transport miRNA to specific CRC cell lines. In addition, evaluate the efficiency of this nano-formulation as a therapeutic candidate for CRC. Bioinformatics tools were used to select a promising tumor suppressor miRNA (mir-497-5p). Green route, using Fusarium oxyporium fungal species, manipulated for the synthesis of SPION@Ag@Cs nanocomposite as a carrier of miR-497-5p. That specifically targets the suppression of PD1/PDL1 and CTLA4pathways for colorectal therapy. UV/visible and FTIR spectroscopy, Zeta potential and MTT were used to confirm the allocation of the miR-497 on SPION@Ag@Cs and its cytotoxicity against CRC cell lines. Immunofluorescence was employed to confirm transfection of cells with miR-497@NPs, and the down- regulation of CTLA4 in HT29, and Caco2 cell lines. On the other hand, PDL1 showed a significant increase in colorectal cell lines (HT-29 and Caco-2) in response to mir497-5p@Nano treatment. The data suggest that the mir-497 -loaded SPION@Ag@Cs nano-formulation could be a good candidate for the suppression of CTLA4in CRC human cell lines. Consequently, the targeting miR-497/CTLA4 axis is a potential immunotherapy treatment strategy for CRC.

Addressing the rising colorectal cancer burden in the older adult: examining modifiable risk and protective factors for comprehensive prevention strategies

BackgroundColorectal cancer is one of the most prevalent and deadly cancer types worldwide. Emerging evidence suggests that high body mass index (BMI) is a significant risk factor for colorectal cancer, particularly among the older adult population. This comprehensive analysis aims to explore the complex epidemiological patterns of colorectal cancer, with a focus on the association between high BMI and disease burden in the older adult.MethodsThe study leveraged data from the Global Burden of Disease (GBD) 2021 study to examine the temporal trends, regional disparities, and the interplay of age, period, and cohort factors in shaping the global colorectal cancer landscape. Epidemiological techniques, including age-period-cohort modeling and joinpoint regression analysis, were employed to provide insights into the potential drivers of the evolving disease burden while controlling for relevant confounding factors.ResultsThe analysis revealed significant geographical disparities in the burden of colorectal cancer among the older adult population. Countries like Uruguay, Monaco, Croatia, Hungary, and Poland exhibited higher mortality and disability-adjusted life-year (DALY) rates, while regions like Bangladesh, Nepal, and much of Africa had relatively lower disease burden. These regional differences are likely attributable to variations in healthcare systems, access to screening and early detection programs, as well as differences in lifestyle behaviors and risk factor prevalence.ConclusionThe strong association between high BMI and colorectal cancer risk, particularly in the older adult population and among men, emphasizes the importance of comprehensive obesity management strategies as part of comprehensive cancer control efforts. Targeted interventions, such as community-based weight management programs and enhanced screening initiatives in high-risk regions, could help mitigate the disproportionate burden of colorectal cancer observed in countries like Monaco, Croatia, and Hungary. Ongoing research and multifaceted public health interventions are crucial to address the growing global burden of colorectal cancer and mitigate the disproportionate impact on vulnerable populations. Strengthening healthcare systems, improving access to quality cancer care, and promoting lifestyle modifications to reduce obesity and other modifiable risk factors should be prioritized to effectively combat this pressing public health challenge.