Metabolomic profiling of upper GI malignancies in blood and tissue: a systematic review and meta-analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis of case-control and cohort human studies evaluating metabolite markers identified using high-throughput metabolomics techniques on esophageal cancer (EC), cancer of the gastroesophageal junction (GEJ), and gastric cancer (GC) in blood and tissue. BACKGROUND: Upper gastrointestinal cancers (UGC), predominantly EC, GEJ, and GC, are malignant tumour types with high morbidity and mortality rates. Numerous studies have focused on metabolomic profiling of UGC in recent years. In this systematic review and meta-analysis, we have provided a collective summary of previous findings on metabolites and metabolomic profiling associated with EC, GEJ and GC. METHODS: Following the PRISMA procedure, a systematic search of four databases (Embase, PubMed, MEDLINE, and Web of Science) for molecular epidemiologic studies on the metabolomic profiles of EC, GEJ and GC was conducted and registered at PROSPERO (CRD42023486631). The Newcastle-Ottawa Scale (NOS) was used to benchmark the risk of bias for case-controlled and cohort studies. QUADOMICS, an adaptation of the QUADAS-2 (Quality Assessment of Diagnostic Accuracy) tool, was used to rate diagnostic accuracy studies. Original articles comparing metabolite patterns between patients with and without UGC were included. Two investigators independently completed title and abstract screening, data extraction, and quality evaluation. Meta-analysis was conducted whenever possible. We used a random effects model to investigate the association between metabolite levels and UGC. RESULTS: A total of 66 original studies involving 7267 patients that met the required criteria were included for review. 169 metabolites were differentially distributed in patients with UGC compared to healthy patients among 44 GC, 9 GEJ, and 25 EC studies including metabolites involved in glycolysis, anaerobic respiration, tricarboxylic acid cycle, and lipid metabolism. Phosphatidylcholines, eicosanoids, and adenosine triphosphate were among the most frequently reported lipids and metabolites of cellular respiration, while BCAA, lysine, and asparagine were among the most commonly reported amino acids. Previously identified lipid metabolites included saturated and unsaturated free fatty acids and ketones. However, the key findings across studies have been inconsistent, possibly due to limited sample sizes and the majority being hospital-based case-control analyses lacking an independent replication group. CONCLUSION: Thus far, metabolomic studies have provided new opportunities for screening, etiological factors, and biomarkers for UGC, supporting the potential of applying metabolomic profiling in early cancer diagnosis. According to the results of our meta-analysis especially BCAA and TMAO as well as certain phosphatidylcholines should be implicated into the diagnostic procedure of patients with UGC. We envision that metabolomics will significantly enhance our understanding of the carcinogenesis and progression process of UGC and may eventually facilitate precise oncological and patient-tailored management of UGC.

The role of sarcopenic obesity for the prediction of prognosis of patients with gastrointestinal cancer.

BACKGROUND: Sarcopenic obesity (SO) in patients with gastrointestinal cancer is associated with a poor prognosis. We aimed to investigate the prognostic impact of SO in patients with gastrointestinal cancer, as well as the diagnostic cut-off value of SO in patients with gastrointestinal cancer among Chinese population. METHODS: We conducted a consecutive cohort study. Between January 2017 and January 2019, 289 patients diagnosed with gastrointestinal cancer were included in our study. Skeletal muscle area, total fat area, and subcutaneous fat area were measured by CT scan. All patients were followed up for 5 years. Receiver operating characteristic curves (ROC) were adopted to determine the cut-off values of visceral fat obesity for the prediction of sarcopenia. Based on the cut-off values, patients with sarcopenia combined with visceral fat obesity were divided into the SO group, and the others were divided into the non-sarcopenic obesity (NSO) group. Kaplan-Meier curves and univariate and multivariate Cox proportional hazard models were employed to explore the associations of body composition profiles with 5-year overall survival and disease-specific survival. RESULTS: Obtained from Youden's Index for ROC for the prediction of 5-year survival, skeletal muscle mass index (SMI) ≤40.02 cm2/m2 with VFA ≥ 126.30 cm2 in men and SMI ≤32.05 cm2/m2 with VFA ≥72.42 cm2 in women indicate a risk of poor prognosis in patients diagnosed with gastrointestinal cancer. Patients with SO had poorer 5-year overall survival (OS) than patients with NSO (6.74% vs. 82.84%, p < 0.001), and poorer 5-year DFS (6.74% vs. 81.82%, p < 0.001). In multivariate analysis, we found that the long-term mortality risk was approximately 13-fold higher among patients in the SO group compared to those with no conditions. CONCLUSIONS: Preoperative assessment of SO is useful not only for monitoring nutritional status but also for predicting 5-year OS in gastrointestinal cancer patients.

Regorafenib synergizes with TAS102 against multiple gastrointestinal cancers and overcomes cancer stemness, trifluridine-induced angiogenesis, ERK1/2 and STAT3 signaling regardless of KRAS or BRAF mutational status.

Single-agent TAS102 (trifluridine/tipiracil) and regorafenib are FDA-approved treatments for metastatic colorectal cancer (mCRC). We previously reported that regorafenib combined with a fluoropyrimidine can delay disease progression in clinical case reports of multidrug-resistant mCRC patients. We hypothesized that the combination of TAS102 and regorafenib may be active in CRC and other gastrointestinal (GI) cancers and may in the future provide a treatment option for patients with advanced GI cancer. We investigated the therapeutic effect of TAS102 in combination with regorafenib in preclinical studies employing cell culture, colonosphere assays that enrich for cancer stem cells, and in vivo. TAS102 in combination with regorafenib has synergistic activity against multiple GI cancers in vitro including colorectal and gastric cancer, but not liver cancer cells. TAS102 inhibits colonosphere formation and this effect is potentiated by regorafenib. In vivo anti-tumor effects of TAS102 plus regorafenib appear to be due to anti-proliferative effects, necrosis and angiogenesis inhibition. Growth inhibition by TAS102 plus regorafenib occurs in xenografted tumors regardless of p53, KRAS or BRAF mutations, although more potent tumor suppression was observed with wild-type p53. Regorafenib significantly inhibits TAS102-induced angiogenesis and microvessel density in xenografted tumors, as well inhibits TAS102-induced ERK1/2 activation regardless of RAS or BRAF status in vivo. TAS102 plus regorafenib is a synergistic drug combination in preclinical models of GI cancer, with regorafenib suppressing TAS102-induced increase in microvessel density and p-ERK as contributing mechanisms. The TAS102 plus regorafenib drug combination may be further tested in gastric and other GI cancers.

Cystatin SN (CST1) Is a Poor Independent Prognostic Biomarker for Gastrointestinal Diffuse Large B-Cell Lymphoma.

BACKGROUND Gastrointestinal diffuse large B-cell lymphoma (GI-DLBCL) is the most common histological subtype of extra-nodal DLBCL, but the risk factors, prognostic biomarkers, histopathological classifications, and treatment strategies have not had significant progress. Emerging evidence shows that cystatin SN (CST1) is involved in tumor progression in several cancer types, but its role in GI-DLBCL has not been revealed. MATERIAL AND METHODS We established a cohort consisting of 84 patients with GI-DLBCL who underwent surgical resection. The expression of CST1 in the cohort was investigated by immunohistochemistry, which divided the patients into subgroups with low or high expression of CST1. Moreover, the CST1 expression in GI-DLBCL tissues or adjacent GI tissues were compared with RT-qPCR. The correlation between CST1 expression and clinicopathological factors was analyzed with the chi-square test. The prognostic significance of CST1 was estimated by univariate and multivariate analysis, and statistical significance was analyzed with the log-rank test. RESULTS CST1 was aberrantly upregulated in GI-DLBCL tissues compared with in non-tumor GI tissues. High expression of CST1 indicated poor prognosis of GI-DLBCL (P=0.012), and CST1 can be regarded as an independent prognostic biomarker of GI-DLBCL (hazard ratio=3.07). In our study, serum lactate dehydrogenase (P=0.002), performance status (P=0.003), Lugano stage (P=0.002), and International Prognostic Index (P=0.001) were also prognostic factors of GI-DLBCL. CONCLUSIONS CST1 is an independent prognostic biomarker of GI-DLBCL, indicating unfavorable prognosis. Our results suggested that CST1 detection can be a promising method to stratify high-risk patients and guide individual treatment.

Impact and potential value of immunosenescence on solid gastrointestinal tumors.

Solid gastrointestinal tumors often respond poorly to immunotherapy for the complex tumor microenvironment (TME), which is exacerbated by immune system alterations. Immunosenescence is the process of increased diversification of immune genes due to aging and other factors, leading to a decrease in the recognition function of the immune system. This process involves immune organs, immune cells, and the senescence-associated secretory phenotype (SASP). The most fundamental change is DNA damage, resulting in TME remodeling. The main manifestations are worsening inflammation, increased immunosuppressive SASP production, decreased immune cell antitumor activity, and the accumulation of tumor-associated fibroblasts and myeloid-derived suppressor cells, making antitumor therapy less effective. Senotherapy strategies to remove senescent cells and block key senescence processes can have synergistic effects with other treatments. This review focuses on immunoenescence and its impact on the solid TME. We characterize the immunosenescent TME and discuss future directions for antitumor therapies targeting senescence.

Survival of advanced/recurrent gastrointestinal stromal tumors treated with tyrosine kinase inhibitors in Taiwan: a nationwide registry study.

BACKGROUND: Most gastrointestinal stromal tumors (GISTs) harbor c-KIT or PDGFRA mutations. Administration of tyrosine kinase inhibitors (TKIs) has significantly improved the survival of patients with GISTs. We aimed to evaluate the clinical outcome of advanced or recurrent GIST patients in Taiwan. METHODS: Patients diagnosed between 2010 and 2020 were enrolled. The collected data included baseline characteristics, treatment pattern, treatment outcome, genetic aberrations and survival status. Progression-free survival (PFS) and overall survival (OS) were analyzed and plotted with the Kaplan-Meier method. Cox regression analysis was used to analyze the prognostic factors of survival. RESULTS: A total of 224 patients with advanced or recurrent GISTs treated with TKIs were enrolled. All patients received imatinib treatment. Ninety-three and 42 patients received sunitinib and regorafenib treatment, respectively. The 48-month PFS and OS rates for patients treated with imatinib were 50.5% and 79.5%, respectively. c-KIT exon 9 and PDGFRA mutations were prognostic factors for a poor PFS and PDGFRA mutation was a prognostic factor for a poor OS in patients treated with imatinib in multivariate Cox regression analysis. The median PFS of patients who received sunitinib treatment was 12.76 months (95% confidence interval (CI), 11.01-14.52). Patients with c-KIT exon 9 mutations had a longer PFS than those with other genetic aberrations. The median PFS of patients treated with regorafenib was 7.14 months (95% CI, 3.39-10.89). CONCLUSIONS: We present real-world clinical outcomes for advanced GIST patients treated with TKIs and identify mutational status as an independent prognostic factor for patient survival.

A novel artificial intelligence network to assess the prognosis of gastrointestinal cancer to immunotherapy based on genetic mutation features.

Background: Immune checkpoint inhibitors (ICIs) have revolutionized gastrointestinal cancer treatment, yet the absence of reliable biomarkers hampers precise patient response prediction. Methods: We developed and validated a genomic mutation signature (GMS) employing a novel artificial intelligence network to forecast the prognosis of gastrointestinal cancer patients undergoing ICIs therapy. Subsequently, we explored the underlying immune landscapes across different subtypes using multiomics data. Finally, UMI-77 was pinpointed through the analysis of drug sensitization data from the Genomics of Drug Sensitivity in Cancer (GDSC) database. The sensitivity of UMI-77 to the AGS and MKN45 cell lines was evaluated using the cell counting kit-8 (CCK8) assay and the plate clone formation assay. Results: Using the artificial intelligence network, we developed the GMS that independently predicts the prognosis of gastrointestinal cancer patients. The GMS demonstrated consistent performance across three public cohorts and exhibited high sensitivity and specificity for 6, 12, and 24-month overall survival (OS) in receiver operating characteristic (ROC) curve analysis. It outperformed conventional clinical and molecular features. Low-risk samples showed a higher presence of cytolytic immune cells and enhanced immunogenic potential compared to high-risk samples. Additionally, we identified the small molecule compound UMI-77. The half-maximal inhibitory concentration (IC50) of UMI-77 was inversely related to the GMS. Notably, the AGS cell line, classified as high-risk, displayed greater sensitivity to UMI-77, whereas the MKN45 cell line, classified as low-risk, showed less sensitivity. Conclusion: The GMS developed here can reliably predict survival benefit for gastrointestinal cancer patients on ICIs therapy.

Adherence with oral nutritional supplements and influencing factors in postoperative patients with digestive tract tumors: a cross-sectional study.

OBJECTIVE: This study aims to use structural equation modeling to explore the pathways and effect sizes of factors influencing the adherence of postoperative patients with digestive tract tumor to oral nutritional supplements, providing a theoretical basis for future nursing intervention measures. METHODS: A total of 300 postoperative patients with digestive tract tumor within 30 days after surgery were conveniently sampled. Surveys were conducted using a General Information Questionnaire, Morisky Medication Adherence Scale, Digestive System Tumor Patient Nutrition Knowledge-Attitude-Behavior Questionnaire, Multidimensional Social Perception Scale, Beliefs about Medical Questionnaire, and General Self-Efficacy Scale. Structural equation modeling was employed to analyze the factors and pathways affecting adherence with oral nutritional supplements. RESULTS: The adherence score of postoperative patients with digestive tract tumor to oral nutritional supplements was 1.61 ± 1.38. The structural equation model had a good fit (χ2/df = 2.685, GFI = 0.930, CFI = 0.913, AGFI = 0.887, IFI = 0.915, and RMSEA = 0.075). Nutrition knowledge, social support, medication beliefs, and self-efficacy were found to be factors influencing adherence with oral nutritional supplements in postoperative patients with digestive tract tumor, with total effects of 0.539, 0.264, 0.215, and 0.180, respectively. Nutrition knowledge indirectly affected adherence through self-efficacy and medication beliefs, while social support indirectly affected adherence through self-efficacy. CONCLUSION: Adherence with oral nutritional supplements in postoperative patients with digestive tract tumor is at a low level. Improving social support, enhancing patients nutrition knowledge, increasing self-efficacy, and strengthening medication beliefs are effective ways to improve patient adherence.

Ultra-Processed Food Consumption as a Risk Factor for Gastrointestinal Cancer and Other Causes of Mortality in Southern Italy: A Competing Risk Approach.

BACKGROUND: Ultra-Processed Foods (UPFs) are increasingly consumed worldwide, even in regions with strong dietary traditions like the Mediterranean and can play a crucial role in the development of chronic diseases, including cancer. This population-based prospective cohort study investigates the association between UPF consumption and gastrointestinal cancers and other causes of mortality in Southern Italy. METHODS: Data were collected from 4870 participants in the MICOL and NUTRIHEP cohorts. The EPIC questionnaire was used to elicit information on food and drink consumption and UPFs were categorized by degree of processing according to the NOVA classification. Cox proportional hazards regression and competing risk models were employed for statistical analysis. RESULTS: UPF consumption was positively associated with all-cause mortality: participants in the 3rd UFP quartile, as compared to the lowest, had a 27% higher risk of death (SHR 1.27 95% CI, 1.03; 1.57), while in the highest quartile as compared to the lowest, the risk was 34% higher (SHR 1.34 95% CI, 1.00; 1.79). Higher UPFs intake was also correlated with an increased gastrointestinal cancers mortality risk, especially the 2nd (SHR 1.65, 95% CI: 1.01; 2.71) and 4th quartile (SHR 3.14 95% CI: 1.56; 6.32), with a dose-dependent effect. For the other cancers, a SHR 1.61 (95% CI 1.03; 2.54) was observed for the 3rd quartile. CONCLUSIONS: Our results reinforce the link between UPF consumption and cancer risk, emphasizing the urgent need for interventions targeting dietary patterns.

Effect of dexamethasone pretreatment using deep learning on the surgical effect of patients with gastrointestinal tumors.

To explore the application efficacy and significance of deep learning in anesthesia management for gastrointestinal tumors (GITs) surgery, 80 elderly patients with GITs who underwent surgical intervention at our institution between January and September 2021 were enrolled. According to the preoperative anesthesia management methodology, patients were rolled into a control (Ctrl) group (using 10 mg dexamethasone 1-2 hours before surgery) and an experimental (Exp) group (using a deep learning-based anesthesia monitoring system on the basis of the Ctrl group), with 40 cases in each group. A comprehensive comparative analysis was performed between the two cohorts, encompassing postoperative cognitive evaluations, Montreal Cognitive Assessment (MoCA) scores, gastrointestinal functionality, serum biomarkers (including interleukin (IL)-6, C-reactive protein (CRP), and cortisol levels), length of hospitalization, incidence of complications, and other pertinent metrics. The findings demonstrated that anesthesia monitoring facilitated by deep learning algorithms effectively assessed the anesthesia state of patients. Compared to the Ctrl group, patients in the Exp group showed significant differences in cognitive assessments (word recall, number connection, number coding) (P<0.05). Additionally, the Exp group exhibited a notably increased MoCA score (25.3±2.4), significantly shorter time to first flatus postoperatively (35.8±13.7 hours), markedly reduced postoperative pain scores, significantly shortened time to tolerate a liquid diet postoperatively (19.6±5.2 hours), accelerated recovery of serum-related indicators, and a significantly decreased mean length of hospital stay (11.4±3.2 days) compared to the Ctrl group. In summary, administering dexamethasone under the anesthesia management of GITs surgery based on gradient boosting decision tree (GBDT) and pharmacokinetics pharmacodynamics (PKPD) models can promote patient recovery, reduce the incidence of postoperative cognitive impairment (POCD), and improve patient prognosis.

Pulmonary tumor thrombotic microangiopathy: Two case reports and literature review.

RATIONALE: Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare but serious complication in patients with malignancy; its main manifestation includes acute pulmonary hypertension with severe respiratory distress. More than 200 cases have been reported since it was first identified in 1990. PTTM accounts for approximately 0.9% to 3.3% of deaths due to malignancy, but only a minority of patients are diagnosed ante-mortem, with most patients having a definitive diagnosis after autopsy. PATIENT CONCERNS: Two middle-aged women both died within a short period of time due to progressive dyspnea and severe pulmonary hypertension. DIAGNOSES: One patient was definitively confirmed as a gastrointestinal malignant tumor by liver puncture biopsy pathology. Ultimately, the clinical diagnosis was pulmonary tumor thrombotic microangiopathy. INTERVENTIONS: The patient was treated symptomatically with oxygen, diuresis, and anticoagulation, while a liver puncture was perfected to clarify the cause. OUTCOMES: Two cases of middle-aged female patients with rapidly progressive pulmonary hypertension and respiratory failure resulted in death with malignant neoplasm. LESSONS: PTTM has a rapid onset and a high morbidity and mortality rate. Our clinicians need to be more aware of the need for timely diagnosis through a targeted clinical approach, leading to more targeted treatment and a better prognosis.

Advances in Foxp3+ regulatory T cells (Foxp3+ Treg) and key factors in digestive malignancies.

Foxp3+ regulatory T cells (Foxp3+ Treg) play a role in regulating various types of tumors, but uncertainty still exists regarding the exact mechanism underlying Foxp3+ Treg activation in gastrointestinal malignancies. As of now, research has shown that Foxp3+ Treg expression, altered glucose metabolism, or a hypoxic tumor microenvironment all affect Foxp3+ Treg function in the bodies of tumor patients. Furthermore, it has been demonstrated that post-translational modifications are essential for mature Foxp3 to function properly. Additionally, a considerable number of non-coding RNAs (ncRNAs) have been implicated in the activation of the Foxp3 signaling pathway. These mechanisms regulating Foxp3 may one day serve as potential therapeutic targets for gastrointestinal malignancies. This review primarily focuses on the properties and capabilities of Foxp3 and Foxp3+Treg. It emphasizes the advancement of research on the regulatory mechanisms of Foxp3 in different malignant tumors of the digestive system, providing new insights for the exploration of anticancer treatments.

Combined Germline and Mosaic SDHA Mutation Is Associated With a Multicancer Syndrome Including Neuroblastoma, Renal Cancer, and Multifocal GI Tumor.

Highlighting here a patient case with neuroblastoma, renal cancer & GIST from germline SDHA.

Patient and Provider Attitudes and Preferences Regarding Early Palliative Care Delivery for Patients with Advanced Gastrointestinal Cancers: A Prospective Survey.

Early integrated palliative care (EIPC) for patients with advanced cancers requires the involvement of family doctors (FDs) and oncologists. We compared attitudes between patients and their providers regarding the delivery of EIPC. Patients with newly diagnosed incurable gastrointestinal (GI) cancer at a tertiary cancer centre in Ontario, Canada, were surveyed using a study-specific instrument regarding the importance of and preferences for accessing support across eight domains of palliative care. Physicians within the circle of care completed a parallel survey for each patient. The concordance between patient and physician responses was analyzed. A total of 66 patients were surveyed (median age 69, 35% female). All had an oncologist, 12% had a specialist palliative care provider (SPC), and 97% had an FD, but only 41% listed the FD as part of the care team. In total, 95 providers responded (oncologist = 68, FD = 21, SPC = 6; response rate 92%; 1-3 physician responses per patient). Disease management and physical concerns were most important to patients. Patients preferred to access care in these domains from oncologists or SPCs. For all other domains, most patients attributed primary responsibility to self or family rather than any healthcare provider. Thus, concordance was poor between patient and physician responses. Across most domains of palliative care, we found low agreement between cancer patients and their physicians regarding responsibilities for care, with FDs appearing to have limited involvement at this stage.

How to Balance Prognostic Factors in Controlled Phase II Trials: Stratified Permuted Block Randomization or Minimization? An Analysis of Clinical Trials in Digestive Oncology.

In controlled phase II trials, major prognostic factors need to be well balanced between arms. The main procedures used are SPBR (Stratified Permuted Block Randomization) and minimization. First, we provide a systematic review of the treatment allocation procedure used in gastrointestinal oncology controlled phase II trials published in 2019. Second, we performed simulations using data from six phase II studies to measure the impacts of imbalances and bias on the efficacy estimations. From the 40 articles analyzed, all mentioned randomization in both the title and abstract, the median number of patients included was 109, and 77.5% were multicenter. Of the 27 studies that reported at least one stratification variable, 10 included the center as a stratification variable, 10 used minimization, 9 used SBR, and 8 were unspecified. In real data studies, the imbalance increased with the number of centers. The total and marginal imbalances were higher with SBR than with minimization, and the difference increased with the number of centers. The efficiency estimates per arm were close to the original trial estimate in both procedures. Minimization is often used in cases of numerous centers and guarantees better similarity between arms for stratification variables for total and marginal imbalances in phase II trials.

[Gastrointestinal mucosa-associated lymphoma]. / Mukosaassoziierte Lymphome des Gastrointestinaltrakts.

Mucosa-associated lymphomas of the gastrointestinal tract are a heterogeneous group differing in pathogenesis, localization and therapeutic options. For all of them, differentiated treatment requires an exact determination of lymphoma stage. For gastric MALT lymphoma, the pathogenetic role of Helicobacter pylori infection has become evident in the last 30 years. These insights were consequently implemented into clinical practice. Nowadays, Helicobacter pylori eradication is the treatment of choice for gastric MALT lymphoma, leading to complete remission of the lymphoma in the majority of cases. In the absence of success, radiotherapy is available in localized stages I/II E with excellent results. Immuno-chemotherapy is the domain for advanced stages III/IV E, and surgery plays no role any more. The rare intestinal and colorectal MALT lymphomas require an individualized therapeutic approach.

Pilot Study by Liquid Biopsy in Gastrointestinal Stromal Tumors: Analysis of PDGFRA D842V Mutation and Hypermethylation of SEPT9 Presence by Digital Droplet PCR.

Tissue biopsy remains the standard for diagnosing gastrointestinal stromal tumors (GISTs), although liquid biopsy is emerging as a promising alternative in oncology. In this pilot study, we advocate for droplet digital PCR (ddPCR) to diagnose GIST in tissue samples and explore its potential for early diagnosis via liquid biopsy, focusing on the PDGFRA D842V mutation and SEPT9 hypermethylated gene. We utilized ddPCR to analyze the predominant PDGFRA mutation (D842V) in surgical tissue samples from 15 GIST patients, correlating with pathologists' diagnoses. We expanded our analysis to plasma samples to compare DNA alterations between tumor tissue and plasma, also investigating SEPT9 gene hypermethylation. We successfully detected the PDGFRA D842V mutation in GIST tissues by ddPCR. Despite various protocols to enhance mutation detection in early-stage disease, it remained challenging, likely due to the low concentration of DNA in plasma samples. Additionally, the results of Area Under the Curve (AUC) for the hypermethylated SEPT9 gene, analyzing concentration, ratio, and abundance were 0.74 (95% Confidence Interval (CI): 0.52 to 0.97), 0.77 (95% CI: 0.56 to 0.98), and 0.79 (95% CI: 0.59 to 0.99), respectively. As a rare disease, the early detection of GIST through such biomarkers is particularly crucial, offering significant potential to improve patient outcomes.