Immune checkpoint inhibitors (ICIs) therapy has been successfully utilized in the treatment of multiple tumors, but only a fraction of patients with gastric cancer (GC) could greatly benefit from it. A recent study has shown that the tumor microenvironment (TME) can greatly affect the effect of immunotherapy in GC. In this study, we established a novel immune risk signature (IRS) for prognosis and predicting response to ICIs in GC based on the TCGA-STAD dataset. Characterization of the TME was explored and further validated to reveal the underlying survival mechanisms and the potential therapeutic targets of GC. The GC patients were stratified into high- and low-risk groups based on the IRS. Patients in the high-risk group, associated with poorer outcomes, were characterized by significantly higher immune function. Further analysis showed higher T cell immune dysfunction and probability of potential immune escape. In vivo, we detected the expressions of SERPINE1 by the quantitative real-time polymerase chain reaction (qPCR)in tumor tissues and adjacent normal tissues. In vitro, knockdown of SERPINE1 significantly attenuated malignant biological behaviors of tumor cells in GC. Our signature can effectively predict the prognosis and response to immunotherapy in patients with GC.

Background: The role of cholesterol metabolism in gastric cancer (GC) and its implications for tumor characteristics and immunotherapy response remain poorly understood. In this study, our aim was to investigate this role, identify associated metabolic subtypes, and assess their clinical implications in GC. Methods: We conducted a comprehensive analysis of cholesterol metabolism genes (CMGs) using transcriptomic data from TCGA and GEO. Based on 23 representative CMGs, we classified GC into metabolic subtypes. We evaluated clinical features and immune cell infiltration between these subtypes. Additionally, we identified a CMG signature and assessed its clinical relevance in GC. We retrospectively enrolled thirty-five GC patients receiving chemotherapy plus a PD-1 inhibitor to assess the CMG signature using multiplex immunohistochemistry. Results: Our analysis revealed two cholesterol metabolism subtypes in GC: Cholesterol Metabolism Type 1 (CMT1) and Cholesterol Metabolism Type 2 (CMT2). These subtypes exhibited distinct patterns: CMT1 indicated heightened cholesterol biosynthesis, while CMT2 showed abnormal cholesterol transport. CMT2 was associated with unfavorable clinical features, enriched malignant pathways, and a pro-tumor immune microenvironment. Furthermore, we developed a five-CMG prognostic signature (ABCA1, NR1H3, TSPO, NCEH1, and HMGCR) that effectively predicted the prognosis of patients with GC and their response to chemotherapy plus a PD-1 inhibitor. This signature was validated in a clinical cohort using multiplex immunohistochemistry. Conclusion: Our results highlight the effectiveness of cholesterol metabolism patterns as biomarkers for predicting the prognosis and immunotherapy response in GC. The expression of cholesterol metabolism genes and the assessment of cholesterol metabolism patterns have the potential to predict the outcome of immunotherapy and guide treatment strategies.

Background: Lymph node metastasis of rectal neuroendocrine tumors (RNETs) predicts poor prognosis. However, the assessment of lymph node metastasis remains a challenge. It has been reported that 68Ga-DOTANOC and 18F-FDG PET-CT scans could be employed in the work-up of rectal neuroendocrine tumors (RNETs). This study aimed to assess both tracers’ ability to identify primary tumors and lymph node (LN) metastasis in RNETs.Methods: A total of 537 patients with RNETs were enrolled from January 2014 to January 2021. Both 68Ga-DOTANOC and 18F-FDG PET-CT scans were used to evaluate primary tumors and LN group metastasis. PET images were evaluated through visual and semiquantitative assessment. Receiver Operating Characteristics (ROC) curve analysis was used to investigate the performance of SUVmax of 68Ga-DOTANOC and 18F-FDG PET in predicting LN group metastasis.Results: Fifty-two patients with preoperative 68Ga-DOTANOC with 18F-FDG PET-CT scans underwent endoscopic biopsy or dissection of the primary tumor, while 11 patients underwent rectal surgery together with regional LN dissection. For primary tumors, 68Ga-DOTANOC had a sensitivity of 89.58% and a positive predictive value (PPV) of 95.56% through visual assessment, while 18F-FDG PET-CT showed 77.08% sensitivity and 97.37% PPV. For the prediction of LN group metastasis, 68Ga-DOTANOC PET-CT had 77.78% sensitivity and 91.67% specificity, while 18F-FDG PET-CT had 38.89% sensitivity and 100% specificity according to visual assessment. The area under the ROC curves (AUC) for 68Ga-DOTANOC PET/CT was 0.852 (95%CI:0.723-0.981) with an optimal SUVmax cut-off value of 2.25, while the AUC for 18F-FDG PET were 0.664 (95%CI:0.415-0.799) with an optimal SUVmax cut-off value of 1.05.Conclusions: This study showed that 68Ga-DOTANOC PET-CT was a promising tool for detecting LN metastasis in RNETs with high sensitivity and specificity in visual assessment and semiquantitative assessment, which was better than 18F-FDG PET-CT.

Background: Lymph node metastasis (LNM) status is an important prognostic factor that strongly influences the treatment decision of early gastric cancer (EGC). This study aimed to evaluate the pattern and clinical significance of LNM in EGC. Methods: A total of 354 patients with carcinoma in situ (n = 42), EGC (n = 312) who underwent radical gastrectomy were enrolled. Their clinicopathological features, pathological reports, and prognostic data were collected and analyzed. Results: The incidence of LNM in all patients was 18.36% (65/354). The rates of D1 and D2 station metastases were 12.10% (43/354) and 6.21% (22/354), respectively. The rates of LNM in absolute indication of endoscopic resection and expanded indication were 3.27% (2/61) and 28.55% (4/14), respectively. Skip LNM was observed in 3.67% (13/354) of patients. For those with middle-third tumor, the metastasis rate of the No. 5 lymph node was 3.05% (5/164). The independent risk factors for LNM were tumors measuring > 30 mm, poorly differentiated tumors, and lymphovascular invasion (all P < 0.05; area under the curve, 0.783). The 5-year disease-free survival rates of patients with and without LNM were 96.26 and 79.17%, respectively (P = 0.011). Tumors measuring > 20 mm and LNM were independent predictive factors for poor survival outcome in all patients. Conclusions: Patients with EGC conforming to expanded indications have a relatively high risk of LNM and may not be suitable for endoscopic submucosal dissection. Pylorus-preserving gastrectomy for patients with middle-third EGC remains controversial due to the high metastasis rate of the No. 5 lymph node.

Background: Epstein–Barr virus (EBV)-associated gastric cancer (EBVaGC) was a unique molecular subtype of gastric cancer (GC). However, the clinicopathological characteristics and prognostic role of EBV infection remains unclear. We aimed to evaluate the clinicopathological features of EBVaGC and its role on prognosis.Methods: EBV-encoded RNA (EBER) in situ hybridization method was used to evaluate the EBV status in GC. The serum tumor markers AFP, CEA, CA19-9 and CA125 of patients were detected before treatment. HER2 expression and microsatellite instability (MSI) status was evaluated according to established criteria. The relationship between EBV infection and clinicopathological factors as well as its role on prognosis were investigated.Results: 420 patients were enrolled in the study and of 53 patients (12.62%) were identified as EBVaGC. EBVaGC was more common in males (p = 0.001) and related to early T stage (p = 0.045), early TNM stage (p = 0.001) and lower level of serum CEA (p = 0.039). No association could be found between EBV infection and HER2 expression, MSI status and other factors (pall > 0.05). Kaplan–Meier analysis revealed that both the overall survival and disease-free survival of EBVaGC patients were similar to that of EBV-negative GC (EBVnGC) patients (p = 0.309 andp = 0.264, respectively).Conclusion: EBVaGC was more common in males and in patients with the early T stage and TNM stage as well as patients with lower serum CEA level. Difference in overall survival and disease-free survival between EBVaGC and EBVnGC patients cannot be detected.

Gastrointestinal Neuroendocrine Neoplasms (GI-NENs) often result in liver metastases, and the role of Primary Tumor Resection (PTR) in managing GI-NENs with liver metastases (GI-NENLM) is still debated. This study aimed to investigate the potential benefits of PTR in treating GI-NENLM by analyzing data from the Surveillance, Epidemiology, and End Results Program (SEER) and the First Affiliated Hospital of Sun Yat-sen University (FAH). The SEER Registry 17 database and the FAH clinical pathology database were used to collect clinicopathology data for GI-NENLM diagnosed between 2010 and 2019 and between 2011 and 2022, respectively. Propensity score matching (PSM) was used to match the clinicopathological characteristics of patients from both cohorts. Inverse probability weighting (IPTW) was used to weigh the PTR and non-PTR groups. The primary endpoint was overall survival (OS). After matching, 155 patients from the SEER database were matched to the FAH cohort. PTR was significantly associated with better prognosis in PSM-matched/unmatched SEER cohorts (P < 0.01) and in the FAH cohort even after eliminating selection bias using IPTW (p < 0.01). Subgroup analysis suggests that the cohort consisting of patients aged 55 years or older, individuals with colorectal primary tumors, those at the T1 disease stage, and those without extrahepatic metastasis may potentially benefit from PTR. Interaction analysis showed no significant interaction between PTR and other clinical and pathological factors except for age. The employment of PTR in patients with GI-NENLM is significantly correlated with individual survival benefits. We support performing PTR on carefully evaluated patients.