Gastrointestinal Tumors Research Articles

Role of NADPH Quinone Reductase 1 (NQO1) Polymorphism in Prevention, Diagnosis, and Treatment of Gastrointestinal Cancers.

Most cancer deaths are related to gastrointestinal (GI) cancers. Several environmental and genetic factors are effective in the occurrence of GI cancers, such as esophageal, stomach, colorectal, liver, and pancreatic cancers. In addition to risk factors related to lifestyle, reactive oxygen species (ROS) also play a role in GI cancers, and an increase in the amount of free radicals can lead to oxidative stress and increase the probability of malignancies. NQO1 is part of the body's antioxidant defense system that protects cells against mutagenesis and carcinogenesis. NQO1 is responsible for reducing quinones to hydroquinone and preventing the generation of ROS by catalyzing the reaction. The existence of single nucleotide polymorphisms (SNPs) of NADPH Quinone Reductase 1 (NQO1), such as 609C>T NQO1, leads to a decrease in NQO1 enzyme activity. Some NQO1 polymorphisms may increase the risk of gastrointestinal cancer. So, the C609T polymorphism in the NQO1 gene has been found to be effective in causing gastrointestinal cancers. On the other hand, it is very important to know the role of biomarkers in the prognosis and management of cancer treatment. Therefore, this study investigated the role of NQO1 as a biomarker in the management of gastrointestinal cancers (prevention, diagnosis and treatment).

A historical cohort study with 27,754 individuals on the association between meat consumption and gastrointestinal tract and colorectal cancer incidence.

In order to explore the association between meat consumption and gastrointestinal/colorectal cancer (CRC) risk and to estimate the Israeli population attributable fraction (PAF), we conducted a collaborative historical cohort study using the individual participant data of seven nutritional studies from the past 6 decades. We included healthy adult men and women who underwent a nutritional interview. Dietary assessment data, using food-frequency or 24-h recall questionnaires, were harmonized. The study file was linked to the National Cancer and death registries. Among 27,754 participants, 1216 (4.4%) were diagnosed with gastrointestinal cancers and 839 (3.0%) with CRC by the end of 2016. Using meta-analysis methods applied to Cox proportional hazard models (adjusted for daily energy intake, sex, age, ethnic origin, education and smoking),100 g/day increments in beef, red meat and poultry consumption, and 50 g/day increment in processed meat consumption were associated with hazard ratios (HRs) and 95% confidence intervals of 1.46 (1.06-2.02), 1.15 (0.87-1.52), 1.06 (0.89-1.26), and 0.93 (0.76-1.12), respectively, for CRC. Similar results were obtained for gastrointestinal cancer, although red meat consumption reached statistical significance (HR = 1.27; 95%CI: 1.02-1.58). The PAFs associated with a reduction to a maximum of 50 g/day in the consumption of red meat were 2.7% (95%CI: -1.9 to 12.0) and 5.2% (0.3-13.9) for CRC and gastrointestinal cancers, respectively. Reduction of beef consumption to a maximum of 50 g/day will result in a CRC PAF reduction of 7.5% (0.7%-24.3%). While beef consumption was associated with gastrointestinal/CRC excess risk, poultry consumption was not. A substantial part of processed meat consumption in Israel is processed poultry, perhaps explaining the lack of association with CRC.

Changes in Skeletal Muscle Mass in the First 3 Months Following Gastrointestinal Cancer Surgery: A Prospective Study.

Surgical resection is the primary treatment for gastrointestinal (GI) cancers, but postoperative skeletal muscle loss (SML) is common and linked to poor prognosis. This study aims to identify patterns of muscle change, examine its association with quality of life (QoL), and explore predictors of SML in the first 3 months. A prospective cohort study was conducted on patients newly diagnosed with GI cancer and undergoing surgery in China between September 2021 and May 2022. Skeletal muscle mass (SMM) and QoL were assessed at admission, 7 days, 1 month, and 3 months post-surgery. Demographic, clinical data, and biomarkers were collected. Missing data were imputed using multiple imputation. Data were analyzed using growth mixture modelling, bivariate analyses, and logistic regression. A total of 483 patients completed baseline assessment. Of the 242 patients with complete muscle assessments, 92% experienced SML. Three distinct patterns of muscle change were identified: 57% had normal preoperative SMM with mild postoperative SML, 16% had low preoperative SMM with moderate SML, and 27% had normal preoperative mass but severe postoperative SML. Moderate/severe SML was associated with more postoperative complications, poorer health, and higher symptom burden. Independent predictors included advanced age, preoperative sarcopenia, advanced cancer stage, and low prognostic nutrition index (PNI ≤ 45). The results did not change when using imputed values. Although SML is prevalent, patterns of muscle change are heterogeneous among patients. Advanced age, preoperative sarcopenia, advanced cancer stage, and cancer-related inflammation are predictors for moderate/severe SML, highlighting the need for early detection and management.

The Relationship between Family Caregiver Burden and Health-Related Quality of Life Among Caregivers of Elderly Patients with Gastrointestinal Cancers

The Relationship between Family Caregiver Burden and Health-Related Quality of Life Among Caregivers of Elderly Patients with Gastrointestinal Cancers

Comparison Between AJCC 8th Edition Gastric and Esophageal ypTNM Classification System in Siewert II Esophagogastric Junction Adenocarcinomas: A Retrospective Study Based on Eastern and Western Data

Multimodal therapy has become the standard treatment for curable upper gastrointestinal cancers. However, it remains unclear which 8th edition AJCC post-neoadjuvant therapy pathological classification system, esophageal (ypTNM-EC) or gastric (ypTNM-GC), can predict the overall survival (OS) of patients with Siewert II adenocarcinomas better. Patients diagnosed with Siewert II adenocarcinomas receiving neoadjuvant therapy plus curative resection at the University Medical Center Utrecht (UMC Utrecht) and the Peking University Cancer Hospital (PUCH) between the 2001 and 2022 were included in this study. The patients from two institutions were analyzed separately. Predictive univariable and multivariable Cox models based on ypTNM-EC and ypTNM-GC were constructed. The C-index and calibration curves were used to compare the predictive abilities of ypTNM-EC and ypTNM-GC Cox models. A total of 125 patients from UMCU and 145 from PUCH were included. There was no significant difference in the C-index between the ypTNM-EC and the ypTNM-GC univariable and multivariable Cox models in the UMC Utrecht (p-value=0.883; p-value=0.681) and PUCH (p-value=0.808; p-value=0.548) cohorts, and no significant difference was observed between their calibration curves in the two cohorts. The AJCC 8th edition ypTNM prognostic classification systems for esophageal and gastric cancer demonstrated no difference in predicting OS for patients with Siewert II adenocarcinomas both in the Western and Eastern data. The ypTNM-GC, with fewer stage groups, may offer greater convenience for clinical application.

Gastrointestinal cancer surgery in the elderly: The effects of preoperative oral nutritional supplements - A retrospective study.

The current study aimed to explore the effect of nutritional prehabilitation on the clinical prognosis of elderly patients undergoing abdominal cancer surgery. A retrospective study was conducted, where participants were divided into two groups based on whether they received oral nutritional supplementation at the first outpatient visit. The nutritional prehabilitation group (n=41) adopted a nutritional prehabilitation mode (a standard energy intake of 25-30 kcal/kg· d was recommended). While the control group (n=55) received routine care. All patients underwent laparoscopic surgery according to the National Comprehensive Cancer Network (NCCN) guidelines. Changes in nutritional status, complications, psychological status, symptoms, hospitalization days, and expenditures were compared between the two groups. Both groups of patients experienced weight loss. However, the decline in body weight in the prehabilitation group was less than that in the control group (-1.88 vs. -2.56 kg, p < 0.001). In the comparison of nutritional prehabilitation group and control group, significant improvements were observed in the Hospital Anxiety Scale scores (5 vs. 5, p = 0.01) and MD Anderson Symptom Inventory scores (3 vs. 0, p < 0.001) respectively. The infection rate in the nutritional prehabilitation group was lower than that in the control group (17.1% vs. 36.4%, p = 0.04). Additionally, patients in the nutritional prehabilitation group had significantly fewer hospitalization days at discharge (14.3 vs. 17.1 days, p = 0.03). In elderly patients undergoing abdominal cancer surgery, a nutritional prehabilitation model may help maintain better physical and mental status, reduce infection rates, and shorten hospitalization days.

Tubular adenoma at the hepatico-jejunal anastomosis in familial adenomatous polyposis (FAP) following pancreaticoduodenectomy: challenges in adenoma surveillance and management.

Upper gastrointestinal tumors, including ampullary adenomas, occur frequently in patients with familial adenomatous polyposis (FAP). Guidelines recommend upper gastrointestinal endoscopy in FAP for surveillance of gastric and duodenal adenomas. However, adenomas can rarely arise from biliary epithelium in patients with FAP. Here, we describe a case of tubular adenoma at the hepatico-jejunal anastomosis with intraductal extension in a patient with FAP and previous pancreaticoduodenectomy. This report illustrates a unique case and emphasizes the need for data on postoperative surveillance in patients with FAP, particularly following pancreaticoduodenectomy.

Fatty Acid Metabolism Signature Contributes to the Molecular Diagnosis of a Malignant Gastric Cancer Subtype with Poor Prognosis and Lower Mutation Burden.

Gastric cancer (GC) is a common gastrointestinal tumor with high morbidity and mortality. Fatty acid metabolism (FAM) contributes to GC development. Patents have been issued for the use of compositions comprising fatty acid analogues for the treatment of many clinical conditions. However, its clinical significance and its relationship with tumor-related mutations have not been thoroughly discovered. This study was conducted to analyze and explore FAM-related genes' molecular characteristics, prognostic significance, and association with tumor- related mutations. The gastric adenocarcinoma's transcriptome, clinical data, and tumor mutation load (TMB) data were downloaded from TCGA and GEO databases. The differentially expressed FAM genes (FAM DEGs) between cancer and control samples were screened, and their correlation with TMB and survival was analyzed. A PPI network of FAM DEGs was constructed, and a downscaling clustering analysis was performed based on the expression of the FAM DEGs. Further immuno- infiltration and GO/KEGG enrichment analyses of the identified FAM clusters were performed to explore their heterogeneity in biological functions. The effects of FAM score and gastric cancer (STAD) on TMB, MSI, survival prognosis, and drug sensitivity were jointly analyzed, and finally, a single-gene analysis of the obtained core targets was performed. Through differential analysis, 68 FAM DEGs were obtained, and they were highly associated with STAD tumor mutation load. In addition, a high FAM DEGs CNV rate was observed. The PPI network showed a complex mutual correlation between the FAM DEGs. Consensus clustering classified the patients into three clusters based on the FAM DEGs, and the clusters presented different survival rates. The GSVA and immune infiltration analysis revealed that metabolism, apoptosis, and immune infiltration-related pathways were variated. In addition, FAM genes, STAD prognostic risk genes, and PCA scores were closely associated with the survival status of STAD patients. FAM score was closely correlated with STAD TMB, MSI, and immunotherapy, and the TMB values in the low FAM score group were significantly higher than those in the high FAM score group. Finally, combining the above results, it was found that the core gene PTGS1 performed best in predicting STAD survival prognosis and TMB/MSI/immunotherapy. Fatty acid metabolism genes affect the development of gastric adenocarcinoma and can predict the survival prognosis, tumor mutational load characteristics, and drug therapy sensitivity of STAD patients, which can help explore more effective immunotherapy targets for GC.

Prognostic impact and reasons for variability by tumor location in gastric cancer

BACKGROUND Gastric cancer (GC) is a highly prevalent gastrointestinal tract tumor. Several trials have demonstrated that the location of GC can affect patient prognosis. However, the factors determining tumor location remain unclear. AIM To investigate the tumor location of patients, we went on to study the influencing factors that lead to changes in the location of GC. METHODS A retrospective evaluation was carried out on 3287 patients who underwent gastrectomy for GC in Zhejiang Cancer Hospital. The patients were followed up post-diagnosis and post-gastrectomy. The clinicopathological variables and overall survival of the patients were recorded. By analyzing the location of GC, the tumor location was divided into four categories: “Upper”, “middle”, “lower”, and “total”. Statistical software was utilized to analyze the relationship of each variable with the location of GC. RESULTS A total of 3287 patients were included in this study. The clinicopathological indices of gender, age, serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen (CA19-9) and CA72-4 levels, were significantly associated with tumor location in patients with GC. In addition, there was a strong correlation between GC location and the prognosis of postoperative patients. Specifically, patients with “lower” and “middle” GC demonstrated a better prognosis than those with tumors in other categories. CONCLUSION The five clinicopathological indices of gender, age, CEA, CA19-9 and CA72-4 levels exhibit varying degrees of influence on the tumor location. The tumor location correlates with patient prognosis following surgery.

Effect of comprehensive management combined with cognitive intervention on patient cooperation and complications during digestive endoscopy

BACKGROUND As lifestyles continue to change worldwide, the incidence of digestive tract carcinoma has gradually increased. Digestive endoscopy is an important tool that can assist in the diagnosis, treatment, and surgical intervention for this disease. However, the examination process is affected by many factors, and patient cooperation is often poor, which can increase the risk of complications. AIM To explore the effects of integrated management and cognitive intervention on cooperation and complications in patients undergoing endoscopy for early gastrointestinal neoplasms. METHODS A total of 354 patients with early stage gastrointestinal cancer who underwent digestive endoscopy procedures between January and December 2023 at our hospital were divided into observation and control groups (177 patients in each group) in a randomized controlled blind trial. The control group received routine interventions, while the observation group received comprehensive integrated management combined with cognitive interventions. We compared the changes in adverse mood, discomfort, examination time, cooperation with the examination, and complications before and after the intervention between the two groups. RESULTS The self-rated anxiety and depression scale scores were lower in the observation group than in the control group (P &lt; 0.05). The visual analog scale scores for discomfort during intubation and examination were also lower in the observation group than in the control group (P &lt; 0.05). Furthermore, the examination time was shorter in the observation group than in the control group (P &lt; 0.05), and the degree of cooperation (94.35%) was higher in the observation group than in the control group (84.75%; P &lt; 0.05). Lastly, the incidence rates of gastrointestinal adverse reactions (10.17% vs 20.34%), choking agitation (14.69% vs 24.86%), abdominal pain (8.47% vs 18.08%), and muscle tension (5.08% vs 14.12%) were all lower in the observation group than in the control group (P &lt; 0.05). CONCLUSION Integrated management and cognitive intervention in early gastrointestinal neoplasm endoscopy alleviate mood, reduce discomfort, shorten examinations, improve cooperation, and reduce complications.

ASO Visual Abstract: Impact of Contemporary Redlining on Healthcare Disparities Among Patients with Gastrointestinal Cancer—A Mediation Analysis

ASO Visual Abstract: Impact of Contemporary Redlining on Healthcare Disparities Among Patients with Gastrointestinal Cancer—A Mediation Analysis

Early Palliative Care Following Aborted Cancer Surgery: Results of a Prospective Feasibility Trial

Background: Although resection is generally necessary for curative-intent treatment of most solid organ cancers, surgery is occasionally aborted due to intraoperative findings. Following aborted cancer surgery, patients have unique care needs that specialized palliative care (PC) providers may be best equipped to manage. We hypothesized that early ambulatory PC referral following aborted cancer surgery would be feasible and acceptable. Methods: This single-institution prospective clinical trial enrolled adult patients with gastrointestinal or hepatopancreatobiliary cancer with no prior PC exposure who had curative-intent oncologic surgery that was unexpectedly aborted. The primary endpoint was the completion of an ambulatory PC consultation within 30 days of enrollment. Secondary outcomes included changes in standardized measures of quality-of-life (QOL) and anxiety/depression during the 3-month follow-up. Results: Among 25 enrolled participants, the mean age was 65.3 ± 9.9 years, 68% were male, and 88% were White. The most common types of cancers were pancreatic (44%), hepatobiliary (20%), and colorectal (12%); reasons for aborting surgery were occult metastatic disease (52%) and local unresectability (36%). Only 13 of 25 (52%) met the primary endpoint of ambulatory PC within 30 days, less than the prespecified threshold of 70%. Overall, 16 (64%) patients completed ambulatory PC consultation a mean of 29.2 ± 15.8 days after enrollment. Of the 9 (36%) who did not, reasons included patient preference (n = 4), withdrawal from study (n = 1), lost to follow-up (n = 1), scheduling conflict (n = 1), and required inpatient PC before discharge (n = 2). Anxiety (4.94 ± 3.56 vs 3.35 ± 2.60, P = 0.06), depression (4.18 ± 4.02 vs 4.76 ± 3.44, P = 0.49), and QOL (82.44 ± 11.41 vs 82.03 ± 15.37, P = 0.92) scores did not significantly differ at 3-month follow-up compared to baseline. Conclusions: Barriers to early ambulatory palliative care consultation exist after aborted cancer surgery. Given the unique and complex care needs of this patient population, additional research is needed to optimize supportive care strategies.

Synthetic Biology-Enabled Engineering of Probiotics for Precision and Targeted Therapeutic Delivery Applications

Probiotics, defined as live microorganisms that offer health benefits when consumed in adequate amounts, have traditionally been used to maintain gastrointestinal (GI) health. They are effective in managing conditions such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and antibiotic-associated diarrhea. Recent research, however, has expanded their potential applications beyond the GI tract to include immune modulation, metabolic regulation, and mental health support. Despite these advances, conventional probiotics face limitations such as instability in harsh environments, lack of precise targeting, and ineffective control over drug release. This review explores the application of synthetic biology in addressing these limitations, emphasizing how tools such as CRISPR-Cas systems, synthetic gene circuits, and plasmid-based mechanisms enhance the stability, functionality, and specificity of engineered probiotics for therapeutic delivery. Applications of synthetic biology-enabled probiotics are examined across a range of health contexts, including GI health, cancer therapy, metabolic disorders, immune modulation, and mental well-being. Synthetic biology tools provide precise genetic modifications that improve the stability, viability, and functionality of engineered probiotics, enabling more targeted therapeutic delivery. Additionally, technologies such as encapsulation support probiotic survival, while gene circuits allow programmable, stimulus-responsive therapeutic release. As synthetic biology continues to advance, the development of programmable probiotics holds promise for personalized, targeted medicine, positioning probiotics as living therapeutics and patient-friendly alternatives to conventional therapeutic delivery systems.

Burden of gastrointestinal cancers among adolescent and young adults in Asia-Pacific region: trends from 1990 to 2019 and future predictions to 2044

Burden of gastrointestinal cancers among adolescent and young adults in Asia-Pacific region: trends from 1990 to 2019 and future predictions to 2044

Review on Ginger Constituents Role in Prevention and Treatment of Gi Cancer

Review on Ginger Constituents Role in Prevention and Treatment of Gi Cancer

Three-year survival follow-up of patients with gastrointestinal cancer treated during the COVID-19 pandemic in Spain: data from the PANDORA-TTD20 study.

The initial SARS-CoV-2 pandemic wave in Spain in 2020 precipitated significant paradigm shifts in gastrointestinal oncology patient management. This study captures the "Zeitgeist" of this period by analyzing adaptive strategies, treatment modifications, and survival outcomes, leveraging a 3-year follow-up perspective to extract insights from this unprecedented experience. We conducted a multicenter, retrospective cohort study utilizing the RETUD-TTD registry, encompassing 703 patients across 19 Spanish centers in April 2020. We evaluated alterations in clinical practice, therapeutic approaches, coronavirus disease 2019 (COVID-19)-related impacts, and patient survival. A Bayesian hierarchical model was employed to identify potential regional-specific frailties. The peak of the pandemic in April 2020 catalyzed substantial shifts in oncological care delivery. Outpatient consultations decreased by 13%, with a notable selection bias toward cases with more favorable prognostic indicators. Multidisciplinary tumor board discussions were significantly curtailed (eg, mean monthly colorectal cancer cases discussed was reduced from 40 to 23), compromising qualitative care measures. This occurred concurrently with an average of over 3 oncologists per center on medical leave. Contrary to initial concerns, the healthcare system demonstrated remarkable resilience. The majority of patients received standard-of-care therapies with regulatory approval, albeit with regimen modifications in 15% of cases. These adaptations included extended dosing intervals, dose intensity modulations, and transitions to oral formulations while maintaining unexpectedly stable long-term survival outcomes. The Bayesian frailty model detected minimal unmeasured prognostic factors related to geographic location, and the type of pandemic-induced adaptation did not significantly impact survival. The model revealed that coronavirus disease 2019's impact was less pronounced than other core prognostic variables. The decentralized Spanish healthcare system exhibited substantial robustness in managing pre-pandemic diagnosed gastrointestinal malignancies, despite asymmetrical, and occasionally severe organizational disruptions. The insights gleaned from this experience could inform future crisis preparedness strategies and optimize care provision during subsequent public health emergencies.

Risk factors for readmission following esophagectomy and gastrectomy for cancer.

Hospital readmission after surgery is a key quality indicator. This nationwide cohort study aimed to assess readmission rates following esophagectomy and gastrectomy for cancer and identify associated risk factors. Data were extracted from the Dutch Upper GI Cancer Audit (DUCA) for patients with esophagogastric cancer who underwent esophagectomy or gastrectomy with curative intent between January 2011 and June 2016. Logistic regression analysis identified risk factors for 30-day readmission. In total, 5566 patients were included. Readmission within 30days occurred in 483 of 3488 (13.8%) patients after esophagectomy and 243 of 2078 patients (11.7%) after gastrectomy. Both minor (Clavien Dindo 1-2) and major (Clavien Dindo ≥3) postoperative complications were independent predictors of readmission after esophagectomy (OR 2.99; 95%CI 2.23-4.02; p< 0.001 and OR 5.20; 95%CI 3.82-7.09; p< 0.001). Specific complications included pulmonary (OR 1.49; 95%CI 1.20-1.85; p< 0.001), gastrointestinal (OR 2.43; 95%CI 1.94-3.05; p< 0.001), and infectious (OR 2.27; 95%CI 1.60-3.22; p< 0.001). Prolonged length of stay (pLOS) was associated with higher readmission rates in patients without complications following esophagectomy (OR 1.91 95% CI 1.19-3.07; p= 0.008), but lower rates in those with complications (OR 0.65 95% CI 0.51-0.83; p< 0.001). For gastrectomy, postoperative complications were also linked to readmission (OR 3.18; 95%CI 2.30-4.40; p< 0.001), particularly gastrointestinal (OR 2.16; 95%CI 1.40-3.32; p< 0.001), and infectious (OR 3.80; 95%CI 2.53-5.71; p< 0.001). Readmission after esophagogastric resection is common, particularly among patients with both minor and major postoperative complications. Prolonged stay after esophagectomy impacts readmission risk differently based on the presence of complications.

A Study of the Risk Factors for 402 Patients with Esophageal Squamous Cell Carcinoma - A Retrospective Comparison with Health Checkup Participants.

Objective Esophageal cancer is a gastrointestinal cancer with a poor prognosis. However, it is curable and can be treated endoscopically if it is detected at an early stage. The objective of this study was to identify the factors that contribute to early detection. Methods From April 2011 to December 2019, we retrospectively investigated consecutive patients diagnosed with esophageal squamous cell carcinoma (ESCC) through upper gastrointestinal endoscopy at two hospitals of Kawasaki Medical University based on medical records. The factors contributing to the early detection of ESCC were investigated by comparing patients with ESCC with those undergoing health checkups in whom no organic lesions were found in the upper gastrointestinal tract on endoscopy (controls). Patients Factors contributing to early detection were examined in 402 ESCC cases and 391 sex- and age-matched controls, and early and advanced cancers were compared along with the risk factors for ESCC. Results A multivariate analysis showed that alcohol consumption and smoking, concomitant cancer of other organs, and a low body mass index (BMI) were factors associated with ESCC (odds ratio [OR], 4.65; 95% confidence interval [CI], 2.880-7.520, OR,3.63; 95% CI, 2.380-5.540, OR, 2.09; 95% CI, 1.330-3.270, OR, 6.38; 95% CI, 3.780-10.800), whereas dyslipidemia was significantly less common in patients with ESCC (OR, 0.545; 95% CI, 0.348-0.853). Comparing early and advanced cancers, a history of endoscopic screening was the only factor involved in early detection (OR, 7.93; 95% CI, 4.480-14.00). Conclusion The factors associated with ESCC include alcohol consumption, smoking, concomitant cancer of other organs, and a low BMI. Endoscopy in subjects with these factors may therefore be recommended for the early detection of ESCC.

Whole-exome sequencing reveals novel genomic signatures and potential therapeutic targets during the progression of rectal neuroendocrine neoplasm.

Rectal neuroendocrine neoplasms (rNENs) are among the most frequent gastrointestinal neuroendocrine neoplasms and pose a serious challenge for clinical management. The size of the primary neoplasm is considered to be the most important predictor of disease progression, but the genetic alterations that occur during the progression of rNENs remain unknown. Here, we performed a comprehensive whole-exome sequencing study on 54 tumor-normal paired, formalin-fixed paraffin-embedded specimens from patients locally diagnosed with rNENs. Of these, 81.5% (n = 44) were classified as small-sized (≤2 cm) rNENs, while the remainder (18.5%, n = 10) were classified as large-sized (>2 cm) rNEN samples. Comparative analysis revealed marked disparities in the mutational landscape between small- and large-sized rNEN samples, and between large-sized rNEN samples with or without lymph node metastases. The high-confidence driver genes RHPN2, MUC16, and MUC4 were significantly mutated in both small- and large-sized rNEN specimens, whereas mutations in MAN2A1, and BAG2 were only identified in large-sized specimens diagnosed with lymph node metastases. Correspondingly, we observed that the mTOR and MAPK pathways were preferentially enriched in the large-sized rNEN specimens. Signature-based analysis revealed that mutational processes associated with defective DNA base excision repair (SBS30) significantly accumulated in large-sized rNEN samples with lymph node metastases, highlighting the important role of this mutagenic process in promoting rNEN progression. We further found that most rNEN subjects, regardless of tumor size, harbored at least one alteration with targeted therapeutic implications. Taken together, these results elucidate the genetic features associated with tumor size and lymphatic metastasis in rNEN patients, which will deepen our understanding of the genetic changes during rNEN progression and potentially directing improvements in rNEN treatment strategies.

Effects of 68Ga-labeled PEG and non-PEG variant peptides as HER2-targeting probes on the progression of gastrointestinal (GI) tumor cells

Effects of 68Ga-labeled PEG and non-PEG variant peptides as HER2-targeting probes on the progression of gastrointestinal (GI) tumor cells