Enhanced Detection of Gastrointestinal Malignancies using Machine Learning-Optimized Liquid Biopsy: A Mini Review.

BACKGROUND: Gastrointestinal (GI) cancers represent some of the most common and lethal malignancies globally, underscoring the urgent need for improved diagnostic strategies. Traditional diagnostic methods, while effective to some degree, are often invasive and unsuit-able for regular screenings. OBJECTIVE: This review article explores integrating machine learning (ML) with liquid biopsy techniques as a revolutionary approach to enhance the detection and monitoring of GI cancers. Liquid biopsies offer a non-invasive alternative for cancer detection through the analysis of circulating tumor DNA (ctDNA) and other biomarkers, which when combined with ML, can significantly improve diagnostic accuracy and patient outcomes. METHODS: We conducted a comprehensive review of recent advancements in liquid biopsy and ML, focusing on their synergistic potential in the early detection of GI cancers. The review addresses the application of next-generation sequencing and digital droplet PCR in enhancing the sensitivity and specificity of liquid biopsies. RESULTS: Machine learning algorithms have demonstrated remarkable ability in navigating complex datasets and identifying diagnostically significant patterns in ctDNA and other circu-lating biomarkers. Innovations such as machine learning-enhanced "fragmentomics" and tomographic phase imaging flow cytometry illustrate significant strides in non-invasive cancer diagnostics, offering enhanced detection capabilities with high accuracy. CONCLUSION: The integration of ML in liquid biopsy represents a transformative step in the early detection and personalized treatment of GI cancers. Future research should focus on overcoming current limitations, such as the heterogeneity of tumor-derived genetic materials and the standardization of liquid biopsy protocols, to fully realize the potential of this technol-ogy in clinical settings.

Methyltransferases in cancer drug resistance: Unlocking the potential of targeting SMYD3 to sensitize cancer cells.

Drug resistance is a significant challenge in oncology and is driven by various mechanisms, among which a crucial role is played by enhanced DNA repair. Thus, targeting DNA damage response (DDR) factors with specific inhibitors is emerging as a promising therapeutic strategy. An important process involved in the modulation of DNA repair pathways, and hence in drug resistance, is post-translational modification (PTM). PTMs such as methylation affect protein function and are critical in cancer biology. Methylation is catalyzed by specific enzymes called protein methyltransferases. In recent years, the SET domain-containing N-lysine methyltransferase SMYD3 has emerged as a significant oncogenic driver. It is overexpressed in several tumor types and plays a signal-dependent role in promoting gastrointestinal cancer formation and development. Recent evidence indicates that SMYD3 is involved in the maintenance of cancer genome integrity and contributes to drug resistance in response to genotoxic stress by regulating DDR mechanisms. Several potential SMYD3 interactors implicated in DNA repair, especially in the homologous recombination and non-homologous end-joining pathways, have been identified by in silico analyses and confirmed by experimental validation, showing that SMYD3 promotes DDR protein interactions and enzymatic activity, thereby sustaining cancer cell survival. Targeting SMYD3, in combination with standard or targeted therapy, shows promise in overcoming drug resistance in colorectal, gastric, pancreatic, breast, endometrial, and lung cancer models, supporting the integration of SMYD3 inhibition into cancer treatment regimens. In this review, we describe the role played by SMYD3 in drug resistance and analyze its potential as a molecular target to sensitize cancer cells to treatment.

Same-Day Positron Emission Tomography/Computed Tomography with 68Ga-Radiolabeled Fibroblast Activation Protein Inhibitors and 18F-Fluorodeoxyglucose Imaging for Gastrointestinal Cancers.

Objective: We investigated the clinical practicability of same-day 68Ga-radiolabeled fibroblast activation protein inhibitors (68Ga-FAPI)-first and 18F-fluorodeoxyglucose (18F-FDG) imaging and compared it with same-day 18F-FDG-first or 2-day procedures in diagnosing gastrointestinal cancers. Materials and Methods: Sixty-five patients with confirmed gastrointestinal cancers were divided into same-day 68Ga-FAPI-first group (Group A), same-day 18F-FDG-first group (Group B), and 2-day group (Group C). Low-dose CT and low injection activity were performed on 68Ga-FAPI positron emission tomography/computed tomography (PET/CT). Interval times, radiation dose, diagnostic performance, and detectability were assessed among groups. Additionally, the uptake, tumor-to-liver ratio (TLR), diagnostic efficacy, and TNM stage were compared between the two modalities. Results: The total waiting time for Group C was significantly longer than that for Group A or B (both p < 0.001). The total dose-length product and effective dose decreased in all groups. There were comparable detectability and diagnostic performance among groups (all p > 0.05). The within-group analysis in Group B indicated that 68Ga-FAPI PET/CT had higher uptake in the primary and recurrent lesions than 18F-FDG without differences in TLR, due to higher liver background on 68Ga-FAPI PET than Group A or C (both p < 0.001).68Ga-FAPI PET/CT possessed higher accuracy than 18F-FDG and changed staging in 14 patients (14/65, 21.54%). Conclusions: The same-day 68Ga-FAPI-first and 18F-FDG imaging reduced examination waiting time without increased radiation dose, simultaneously achieving excellent diagnostic performance and improving clinical staging in diagnosing gastrointestinal cancers.

Establishment and validation of a risk prediction model for sarcopenia in gastrointestinal cancer patients: A systematic review and meta-analysis-based approach.

OBJECTIVE: The study aimed to develop a model to predict the risk of sarcopenia in gastrointestinal cancer patients. The goal was to identify these patients early and classify them into different risk categories based on their likelihood of developing sarcopenia. METHODS: This study evaluated risk factors for sarcopenia in patients with gastrointestinal cancers through a systematic review and meta-analysis. The natural logarithm of the combined risk estimate for each factor was used as a coefficient to assign scores within the model for risk prediction. Data from 270 patients with gastrointestinal cancers, collected between October 2023 and April 2024, was used to assess the predictive performance of the scoring model. RESULTS: The analysis included 17 studies that included 9405 patients with gastrointestinal cancers, out of which 4361 had sarcopenia. The model identified several significant predictors of sarcopenia, including age (OR = 2.45), sex (OR = 1.15), combined diabetes (OR = 2.02), neutrophil-to-lymphocyte ratio (NLR) category (OR = 1.61), TNM stage (OR = 1.61), and weight change (OR = 1.60). Model validation was performed using an external cohort through logistic regression, resulting in an area under the curve (AUC) of 0.773. This model attained a sensitivity of 0.714 and a specificity of 0.688 and ultimately selected 16.5 as the ideal critical risk score. Furthermore, an AUC of 0.770 was obtained from Bayesian model validation; the optimal critical risk score was determined to be 19.0, which corresponds to a sensitivity of 0.658 and a specificity of 0.847. CONCLUSIONS: The model of risk prediction developed through systematic review and meta-analysis demonstrates substantial for sarcopenia in patients with gastrointestinal cancers. Its clinical usability facilitates the screening of patients at high risk for sarcopenia.

An atlas on risk factors for gastrointestinal cancers: A systematic review of Mendelian randomization studies.

OBJECTIVE: Gastrointestinal cancers are one of the most frequent cancer types and seriously threaten human life and health. Recent studies attribute the occurrence of gastrointestinal cancers to both genetic and environmental factors, yet the intrinsic etiology remains unclear. Mendelian randomization is a powerful well-established statistical method that is based on genome-wide association study (GWAS) to evaluate the causal relationship between exposures and outcomes. In the present study, we aimed to conduct a systematic review of Mendelian randomization studies investigating any causal risk factors for gastrointestinal cancers. METHODS: We systematically searched Mendelian randomization studies that addressed the associations of genetically predicted exposures with five main gastrointestinal cancers from September 2014 to March 2024, as well as testing the research quality and validity. RESULTS: Our findings suggested robust and consistent causal effects of body mass index (BMI), basal metabolic rate, fatty acids, total cholesterol, total bilirubin, insulin like growth factor-1, eosinophil counts, interleukin 2, alcohol consumption, coffee consumption, apolipoprotein B on colorectal cancer risks, BMI, waist circumference, low-density lipoprotein (LDL), total testosterone, smoking on gastric cancer risks, BMI, fasting insulin, LDL, waist circumference, visceral adipose tissue (VAT), immune cells, type 2 diabetes mellitus (T2DM) on pancreatic cancer risks, waist circumference, smoking, T2DM on esophageal adenocarcinoma risks, and VAT, ferritin, transferrin, alcohol consumption, hepatitis B virus infection, rheumatoid arthritis on liver cancer risks, respectively. CONCLUSION: Larger, well-designed Mendelian randomization studies are practical in determining the causal status of risk factors for diseases.

Association of dietary inflammatory index and dietary oxidative balance score with gastrointestinal cancers in NHANES 2005-2018.

BACKGROUND&AIMS: Gastrointestinal (GI) cancers, including gastric, liver, esophageal, pancreatic, and colorectal cancers, represent significant global health burdens. Emerging evidence suggests that dietary patterns, particularly their inflammatory and oxidative properties, may influence cancer risk. The Dietary Inflammatory Index (DII) and Dietary Oxidative Balance Score (DOBS) assess the inflammatory and oxidative effects of diets, respectively. This study aims to explore the association between DII, DOBS, and the combined risk of GI cancers, and investigates the potential mediating roles of serum albumin and red cell distribution width (RDW). METHODS: Data from 26,320 participants in the NHANES 2005-2018 cycles were analyzed. DII was calculated based on 28 dietary components, and DOBS included 17 nutrients (3 pro-oxidants and 14 antioxidants). Logistic regression models assessed the associations between DII, DOBS, and GI cancers. Restricted cubic spline (RCS) models examined dose-response relationships. Mediation analysis evaluated the roles of serum albumin and RDW. Subgroup analyses explored interactions with demographic and health-related factors. RESULTS: Higher DII was associated with increased GI cancer risk (OR: 1.26, 95% CI: 1.07-1.49 per unit increase), while higher DOBS was associated with reduced risk (OR: 0.90, 95% CI: 0.76-0.99 per unit increase). RCS analysis indicated a significant nonlinear relationship between DII and GI cancer risk. Serum albumin and RDW partially mediated the associations between DII, DOBS, and GI cancers. Subgroup analyses showed stronger associations for DII among certain demographics, and significant interactions were found between DII and BMI. For DOBS, significant interactions were observed with age and BMI. CONCLUSION: This study reveals significant associations between dietary inflammatory and oxidative balance scores and GI cancer risk. Higher DII is linked to increased risk, while higher DOBS is protective. The mediating roles of serum albumin and RDW provide insights into underlying mechanisms. These findings underscore the potential of dietary modifications in GI cancer prevention and management, emphasizing the importance of anti-inflammatory and antioxidant-rich diets.

No genetic causality between appendectomy and gastrointestinal cancers: a Mendelian randomization study and meta-analysis in European population.

The impact of appendectomy on the risk of gastrointestinal cancers remains unknown. We aimed to systematically estimate the causal relationship between appendectomy and gastrointestinal cancers in the European population using two-sample Mendelian randomization (TSMR) study methods and meta-analysis. As part of the discovery cohort analysis, we identified independent genetic variants strongly associated with appendectomy from the UK Biobank (50,105 cases) to serve as instrumental variables (IVs). Summary-level data for gastrointestinal cancers were obtained from the FinnGen study. As the replication cohort, IVs associated with appendectomy were extracted in the FinnGen study (28,601 cases). The data for gastrointestinal cancers were obtained from the UK Biobank. Finally, meta-analyses were conducted to evaluate the combined causal effects of the MR results. We found no causal relationship between appendectomy and gastrointestinal cancers in both the discovery and replication cohorts. Finally, the meta-analysis revealed no causal association between appendectomy and gastrointestinal cancers. Our findings suggest no causal relationship exists between appendectomy and gastrointestinal cancers in the European population. This genetic evidence supports the conclusion from other observational studies that appendectomy does not affect the risk of gastrointestinal cancers in the European population.

CAR-NK cells for gastrointestinal cancer immunotherapy: from bench to bedside.

BACKGROUND: Gastrointestinal (GI) cancers represent a significant health burden worldwide. Their incidence continues to increase, and their management remains a clinical challenge. Chimeric antigen receptor (CAR) natural killer (NK) cells have emerged as a promising alternative to CAR-T cells for immunotherapy of GI cancers. Notably, CAR-NK cells offer several advantages, including reduced risk of graft-versus-host disease, lower cytokine release syndrome, and the ability to target cancer cells through both CAR-dependent and natural cytotoxic mechanisms. MAIN BODY: This review comprehensively discusses the development and applications of CAR-NK cells in the treatment of GI cancers. We explored various sources of NK cells, CAR design strategies, and the current state of CAR-NK cell therapy for GI cancers, highlighting recent preclinical and clinical trials. Additionally, we addressed existing challenges and propose potential strategies to enhance the efficacy and safety of CAR-NK cell therapy. CONCLUSIONS: Our findings highlight the potential of CAR-NK cells to revolutionize GI cancer treatment and pave the way for future clinical applications.

Association Between Type 1 Diabetes Mellitus and Incident Gastrointestinal Cancer in Korean Population: A Nationwide Retrospective Cohort Study.

BACKGROUND: The age-standardised incidence ratio of gastrointestinal cancers in type 1 diabetes (T1D) patients has been reported to be higher than that in the general population. After adjusting for shared risk factors, we aimed to explore the association between T1D and gastrointestinal cancer and examine how this relationship varies by age and sex. MATERIALS AND METHODS: This retrospective cohort study included 268,179 participants from the Korean National Health Insurance Service-National Sample Cohort. The primary outcome is the incident of gastrointestinal cancers, based on diagnostic codes. Multivariate Cox regression analyses were performed to assess the association between T1D and gastrointestinal cancers. RESULTS: Of the 268,179 participants, 2681 had T1D at baseline and were followed for 12.98 (± 2.92) years. Compared with non-T1D, T1D patients had a significantly increased risk of all gastrointestinal cancer (adjusted hazard ratio [aHR]: 1.403, 95% confidence interval [CI]: 1.253-1.573). T1D patients increased risks of oesophageal cancer (aHR: 1.864, 95% CI: 1.038-3.349), gastric cancer (aHR: 1.313, 95% CI: 1.066-1.616), colon cancer (aHR: 1.365, 95% CI: 1.110-1.678), liver cancer (aHR: 1.388, 95% CI: 1.115-1.727), and pancreatic cancer (aHR: 1.716, 95% CI: 1.182-2.492). The consistency of this association persisted among both male and female, with its strength increasing with older age. CONCLUSIONS: The risk of gastrointestinal cancer was significantly increased in T1D patients. Older male T1D patients exhibit a higher risk, suggesting the need for targeted attention in their care.

Deregulation of TWIST1 expression by promoter methylation in gastrointestinal cancers.

TWIST1, a basic helix-loop-helix transcription factor with versatile roles in cancer, is frequently deregulated in cancers, through established pathway perturbations. However. the significance of TWIST1 methylation in the deregulation of TWIST1 in gastrointestinal cancers is not fully clear. This study hypothesized that TWIST1 promoter methylation deregulates TWIST1 expression independent of established deregulators such as the WNT, TGFB, NOTCH and miRNA pathways. To prove this hypothesis, colon, gastric and rectal cancer genomic data comprising gene expression, DNA methylation, and miRNA data were retrieved from the Cancer Genome Atlas cohorts which are publicly available in cancer genomic databases, the Genome Data Commons and the cBioportal.org. About 217 variables comprising expression levels of genes of the WNT, TGFB, NOTCH and miRNA signalling pathways, as well as the beta values of 17 TWIST1 methylation loci were subjected to Principal Component Regression Analysis, and then standard Linear Regression Analysis. The results showed that TWIST1 methylation is a predictor of TWIST1 expression in the gastrointestinal cancers, independent of WNT, TGFB, and NOTCH signalling and miRNA deregulation. The results also showed that different TWIST1 methylation loci may deregulate TWIST1 expression in different cancer types. The inference that can be drawn from this study is that TWIST1 DNA methylation is an important TWIST1 deregulation mechanism in colon, rectal and gastric cancers.

Reasons for Surgical Attrition Among Nonmetastatic Upper Gastrointestinal Cancer Patients: A Single Institutional Experience.

INTRODUCTION: Upper gastrointestinal (UGI) cancers require multidisciplinary treatment, but surgery provides the only potentially curative option. We sought to understand reasons for attrition before surgery within our regional hospital network. METHODS: We performed chart reviews of patients (age 18-80) with stage I-III UGI cancers (gastroesophageal junction, gastric, and hepatopancreatobiliary adenocarcinomas) in our multihospital cancer registry from 2015 to 2021. Our primary outcome was reasons for surgical attrition. Univariable analysis identified factors related to surgical attrition and the Kaplan-Meier method estimated overall survival based on surgery receipt. RESULTS: Seven hundred and ninety-two patients were included in our analysis, of whom 107 (13.5%) did not undergo curative surgery. Reasons for not undergoing surgery included medical comorbidities (30.8%), patient preference/nonmedical barriers (24.3%, which included: not interested without further explanation, worried about complications, nonadherence to appointments, insurance issues, did not wish for blood transfusion, lack of social support, preferring home care, and worried about recurrence), psychosocial (5.6%), progression while on neoadjuvant therapy or waiting for transplant (15.0% and 7.5%), poor performance status (3.7%), side effects of neoadjuvant therapy (3.7%), and death unrelated to treatment or unknown cause (9.4%). Nonsurgical management was not associated with race, socioeconomic status, or distance traveled for care. Survival was greatly improved for patients who underwent surgery (158 vs. 63 weeks, p < 0.05). CONCLUSION: Nearly one in seven patients (18-80 years old) with UGI cancers evaluated at our academic cancer center did not undergo surgical resection. Reasons for surgical attrition included potentially modifiable issues, and addressing these barriers could help overcome inequities in cancer treatment and survival.

Thematic analysis of patient perspectives in a randomized controlled trial for a remote perioperative telemonitoring program.

BACKGROUND: Remote patient telemonitoring programs offer the potential to enhance access and communication with medical providers. This study assessed the patient-reported experience during perioperative telemonitoring for gastrointestinal (GI) oncologic surgery. METHODS: Between October 2021 and July 2023, patients with GI cancer were enrolled in the remote telemonitoring trial and randomized into the intervention or enhanced usual care arm. Although the enhanced usual care arm adhered to standard protocols for problem reporting, the intervention arm received active nursing support for monitoring data deviations from predetermined thresholds. The program culminated in a 15-minute exit interview comprised 9 total questions to gather insights into the patient experiences with device usage, symptom reporting, and communication with the healthcare team. Thematic analysis was conducted on all responses to present a patient-centric summary. RESULTS: Of the 114 patients completing the study, 100 patients (88%) participated in the exit interview. Most enrolled patients (n = 68) were diagnosed as having colorectal cancer. The intervention arm reported greater ease and accessibility in electronic data reporting and communication with healthcare team compared to the enhanced usual care arm (94% vs 69%). Qualitative analysis identified 3 themes used to describe the program: "instilling an affirmative and proactive mindset toward recovery," "receiving timely attention from healthcare team," and "benefits of device usage and electronic health surveys." The subthemes highlighted an appreciative and empowering mindset among most patients. CONCLUSION: Most enrolled patients expressed satisfaction with the program to facilitate their postoperative recovery. These positive testimonials present a promising outlook for future implementation from the patient perspective.

Admission Pattern of Gastrointestinal Cancer for 2020-2023 From a Single Tertiary-Care Hospital in Pune, Western Maharashtra.

The prevalence of gastrointestinal (GI) cancer is increasing across diverse regions of India, demanding further investigation at the state level. In response, a new department of surgical gastroenterology was started at a tertiary-care hospital in Pune, Western Maharashtra, in 2019. The objective of this study was to explore the pattern of admissions in terms of demographics and types of GI cancers over the last four years (i.e., 2020-2023). Retrospective admissions data were collected from hospital records for 2020-2023. A total of 2294 patients were treated at the outpatient department (OPD), and 135 patients were admitted to the inpatient department (IPD). The data comprised OPD/IPD admissions, age, gender, diagnosis, and length of stay (LoS). In addition to basic statistical reporting, t-tests were used to explore differences among the study variables. Out of 135 GI cancer patients, 57% were male. The mean age of inpatients per year ranged from 53 to 60 years, with an average age of 56.35 ± 10.14 years. The average LoS was 12.31 ± 9.39 days. From 2020 to 2023, the number of admissions increased from 5 to 57. The increase was more pronounced in men than women (57% vs. 43%, respectively). Furthermore, increased admission of younger patients was observed, and the average LoS decreased from 17 to 11 days from 2020 to 2023, respectively. A statistically significant difference in LoS (p = 0.023) was observed based on gender, where LoS was longer for women than for men on average (13.5 ± 10.8 vs. 9.46 ± 8.28, respectively). As GI cancer incidence is predicted to continue to increase in India, these new estimates will help to plan cancer prevention and control through intervention via early detection and management.

MicroRNA-155 and its exosomal form: Small pieces in the gastrointestinal cancers puzzle.

Gastrointestinal (GI) cancers are common cancers that are responsible for a large portion of global cancer fatalities. Due to this, there is a pressing need for innovative strategies to identify and treat GI cancers. MicroRNAs (miRNAs) are short ncRNAs that can be considered either cancer-causing or tumor-inhibiting molecules. MicroRNA-155, also known as miR-155, is a vital regulator in various cancer types. This miRNA has a carcinogenic role in a variety of gastrointestinal cancers, including pancreatic, colon, and gastric cancers. Since the abnormal production of miR-155 has been detected in various malignancies and has a correlation with increased mortality, it is a promising target for future therapeutic approaches. Moreover, exosomal miR-155 associated with tumors have significant functions in communicating between cells and establishing the microenvironment for cancer in GI cancers. Various types of genetic material, such as specifically miR-155 as well as proteins found in cancer-related exosomes, have the ability to be transmitted to other cells and have a function in the advancement of tumor. Therefore, it is critical to conduct a review that outlines the diverse functions of miR-155 in gastrointestinal malignancies. As a result, we present a current overview of the role of miR-155 in gastrointestinal cancers. Our research highlighted the role of miR-155 in GI cancers and covered critical issues in GI cancer such as pharmacologic inhibitors of miRNA-155, miRNA-155-assosiated circular RNAs, immune-related cells contain miRNA-155. Importantly, we discussed miRNA-155 in GI cancer resistance to chemotherapy, diagnosis and clinical trials. Furthermore, the function of miR-155 enclosed in exosomes that are released by cancer cells or tumor-associated macrophages is also covered.

The relationship between the tertiary lymphoid structure and immune-infiltrating cells in gastrointestinal cancers: A systematic review and meta-analysis.

OBJECTIVES: This study systematically evaluated the relationship between tertiary lymphoid structures (TLS) and clinical pathological features as well as immune infiltrating cells in gastrointestinal cancers. METHODS: We searched Web of science, Pubmed, Embase, and Cochrane Library for studies that met the requirements as of July 1, 2023, and the odds ratio, the corresponding 95% confidence interval or mean and standard deviation, were included in the analysis. FINDINGS: We eventually included 20 studies, involving a total of 4856 patients. TLS were found to be significantly associated with T stage, N stage, TNM stage, and tumor size. Moreover, patients with positive TLS showed significantly elevated expression of T-cell related markers, including CD3, CD4, CD8, CD45RO; B-cell related markers, such as CD11c and CD20; and dendritic cell-related marker CD103. On the other hand, positive TLS correlated significantly with low expression of FOXP3 and CD68. Additionally, there was a significant positive association between TLS and overall infiltration of tumor-infiltrating lymphocytes. CONCLUSION: The presence of TLS is significantly correlated with the infiltration of various immune cells in gastrointestinal cancers. To determine the ideal balance between the presence of mature TLS and appropriate immune cell infiltration, further high-quality and multicenter clinical studies need to be conducted.

Food Insecurity and Dietary Quality in African American Patients with Gastrointestinal Cancers: An Exploratory Study.

African American (AA) individuals experience food insecurity at twice the rate of the general population. However, few patients are screened for these measures in the oncology setting. The primary aim of this study was to evaluate associations between food insecurity and dietary quality in AA patients with gastrointestinal (GI) malignancies. The secondary aim was to evaluate differences in dietary quality and the level of food insecurity between the participants at Temple University Hospital (TUH) vs. Fox Chase Cancer Center (FCCC). A single-arm, cross-sectional study was conducted, in which 40 AA patients with GI malignancies were recruited at FCCC and TUH between February 2021 and July 2021. Participants completed the US Adult Food Security Survey Module to assess the level of food security (food secure vs. food insecure). An electronic food frequency questionnaire (VioScreenTM) was administered to obtain usual dietary intake. Diet quality was calculated using the Healthy Eating Index 2015 (HEI-2015). Dietary quality and food insecurity were summarized using standard statistical measures. Overall, 6 of the 40 participants (15%) reported food insecurity, and the mean HEI-2015 score was 64.2. No association was observed between dietary quality and food insecurity (p = 0.29). However, we noted that dietary quality was significantly lower among patients presenting at TUH (mean HEI-2015 = 57.8) compared to patients at FCCC (mean HEI-2015 = 73.5) (p < 0.01). Food insecurity scores were also significantly higher in the TUH population vs. the FCCC population (p < 0.01).

ZNF8 promotes progression of gastrointestinal cancers via a p53-dependent mechanism.

p53 is a critical tumor suppressor, and the disruption of its normal function is often a prerequisite for the development or progression of tumors. Our previous works revealed that multiple members of Krüppel-associated box (KRAB) domain zinc-finger proteins (KZFPs) family regulate p53 transcriptional activity by interacting with it. But the tumor biology functions of these members have not been fully elucidated. Here, the pan-cancer analysis related to gastrointestinal cancers (GICs) revealed that ZNF8, a p53-interacting protein, is an unfavorable prognostic factor for patients with malignancies. ZNF8 interacts with p53 and further depresses its transcriptional activity in colon cancer cells. The knockdown of ZNF8 or the overexpression of ZNF8 inhibits or facilitates the in vitro colony formation, migration, invasion, and angiogenesis of p53+/+ colon cancer HCT116 cells, HepG2 cells and EC109 cells rather than p53-/- colon cancer HCT116 cells and p53-knockout HepG2 cells, respectively. Xenograft experiments conducted in vivo also showed that the knockdown of ZNF8 in p53+/+ but not in p53-/- HCT116 cells curbs the tumor growth and metastasis to lung, leading to an extended life span for tumor-bearing mice. Clinically, two independent immunohistochemistry cohorts of colon cancer and esophageal cancer also indicated that ZNF8 is higher expression in carcinoma tissues than adjacent tissues and this is associated with worse overall survival outcomes in patients without harboring p53 mutation. Together, our results provide insight into the p53-specific tumor oncogenic function of ZNF8. ZNF8 may prove to be a potential target for GICs treatment.

Targeting non-histone methylation in gastrointestinal cancers: From biology to clinic.

Gastrointestinal (GI) cancers, encompassing a range of malignancies within the digestive tract, present significant challenges in both diagnosis and treatment, reflecting a dire need for innovative therapeutic strategies. This article delves into the profound influence of non-histone methylation on the pathogenesis and evolution of gastrointestinal (GI) cancers. Non-histone proteins, undergoing methylation by enzymes such as Protein Arginine Methyltransferases (PRMTs) and Lysine Methyltransferases (KMTs), play pivotal roles in cellular signaling, metabolism, chromatin remodeling, and other processes crucial for cancer development. This review illuminates the complex mechanisms by which non-histone methylation affects key aspects of tumor biology, including oncogenesis, growth, proliferation, invasion, migration, metabolic reprogramming, and immune escape in GI malignancies. Highlighting recent discoveries, this work underscores the importance of non-histone methylation in cancer biology and its potential as a target for innovative therapeutic strategies aimed at improving outcomes for patients with GI cancers.

Metabolic dysfunction-associated steatotic liver disease and extrahepatic gastrointestinal cancers.

Metabolic dysfunction-associated steatotic liver disease (MASLD) poses a significant and ever-increasing health and economic burden worldwide. Substantial epidemiological evidence shows that MASLD is a multisystem disease that is associated not only with liver-related complications but is also associated with an increased risk of developing cardiometabolic comorbidities and extrahepatic cancers (principally gastrointestinal [GI] cancers). GI cancers account for a quarter of the global cancer incidence and a third of cancer-related deaths. In this narrative review, we provide an overview of the literature on (a) the epidemiological data on the risk of non-liver GI cancers in MASLD, (b) the putative mechanisms by which MASLD (and factors linked with MASLD) may increase this risk, and (c) the possible pharmacotherapies beneficially affecting both MASLD and extrahepatic GI cancer risk. There are multiple potential pathophysiological mechanisms by which MASLD may increase extrahepatic GI cancer risk. Although further studies are needed, the current evidence supports a possible extrahepatic carcinogenic role for MASLD, regardless of obesity and diabetes status, thus highlighting the potential role of tailoring cancer screening for individuals with MASLD. Although there are conflicting data in the literature, aspirin, statins and metformin appear to exert some chemo-preventive effects against GI cancer.

Targeting the Wnt/ß-catenin signal pathway for the treatment of gastrointestinal cancer: Potential for advancement.

Gastrointestinal cancers (GICs) are highly prevalent cancers that threaten human health worldwide. The Wnt/ß-catenin signaling pathway has been reported to play a pivotal role in the carcinogenesis of GICs. Numerous interventions targeting the Wnt/ß-catenin signaling in GICs are currently being tested in clinical trials with promising results. Unfortunately, there are no clinically approved drugs that effectively target this pathway. This comprehensive review aims to evaluate the impact of clinical therapies targeting the Wnt/ß-catenin signaling pathway in GICs. By integrating data from bioinformatics databases and recent literature from the past five years, we examine the heterogeneous expression and regulatory mechanisms of Wnt/ß-catenin pathway genes and proteins in GICs. Specifically, we focus on expression patterns, mutation frequencies, and clinical prognoses to understand their implications for treatment strategies. Additionally, we discuss recent clinical trial efforts targeting this pathway. Understanding the inhibitors currently under clinical investigation may help optimize foundational research and clinical strategies. We hope that elucidating the current status of precision therapeutic stratification for patients targeting the Wnt/ß-catenin pathway will guide future innovations in precision medicine for GICs.