Mingxu Da

This article presents a 60-year-old woman presented with a one-year history of abdominal distension, which acutely worsened over four days prior to admission. Imaging revealed a large retroperitoneal liposarcoma. Exploratory laparotomy identified a massive tumor (approximately 45×40×13 cm, weighing 8 kg) invading the left kidney, adrenal gland, adnexa, left hemicolon, and mesentery. En bloc resection was performed. Postoperative pathology combined with fluorescence in situ hybridization (FISH) testing demonstrated MDM2/CDK4 amplification, confirming dedifferentiated liposarcoma (DDLPS). The patient recovered well postoperatively and was discharged following adjuvant radiotherapy (IMRT; 50 Gy in 25 fractions), chemotherapy (AD regimen), and immunotherapy (sintilimab).Through this case, we mainly understand the characteristics of the disease onset, special diagnosis, and main treatment methods.

To investigate the expression levels of high mobility group box 1 (HMGB1) and nuclear factor kappa-B (NF-κB) and to characterize their relationship in gastric adenocarcinoma. The expression data for HMGB1 and NF-κB from the GEO database were analyzed to assess expression levels and prognostic relevance in gastric cancer. Immunohistochemistry was performed to verify their expressions in primary gastric adenocarcinoma tissues and adjacent non-tumor tissues. Next, we collected clinicopathologic data of patients with gastric cancer and analyzed the correlations between HMGB1 and NF-κB expression. Furthermore, we assessed the impact of HMGB1 and NF-κB expression on the survival time of gastric cancer patients using Kaplan-Meier survival analysis. All statistical analyses were conducted using GraphPad Prism 9. The results showed that HMGB1 and NF-κB were significantly higher than normal tissues, which were significantly correlated with survival prognosis. IHC analysis further confirmed high positivity rates for HMGB1 (81.76%) and NF-κB (75%) in gastric adenocarcinoma, respectively. Furthermore, higher expression levels of HMGB1 and NF-κB were associated with shorter survival time of gastric cancer patients. The expression level of HMGB1 or NF-κB was correlated with tumor size, depth of invasion, and clinical stage. Finally, we demonstrated that there is a correlation between the expression of HMGB1 and NF-κB. Previous studies focused on mechanistic regulation, while systematic clinicopathologic co-expression analysis of HMGB1 and NF-κB in human gastric adenocarcinoma tissues remains limited. This work provides novel evidence that the co-expression of HMGB1 and NF-κB is associated with key clinicopathologic factors and survival outcomes in gastric adenocarcinoma.

Neuropilin-1 (NRP1) is overexpressed in various malignant solid tumors, modulating the tumor microenvironment (TME) via multiple mechanisms to promote immune suppression, angiogenesis, and epithelial-mesenchymal transition (EMT), ultimately resulting in poor patient survival. Autophagy, a highly conserved cellular self-degradation process, plays a stage-dependent, bidirectional role in cancer. At early stages it suppresses tumorigenesis by clearing damaged cellular components, whereas at advanced stages it supports tumor survival under stress and thereby enhances proliferation, invasiveness, and therapy resistance. The interplay between NRP1 and autophagy in the TME is characterized by reciprocal regulation: NRP1 activates certain pathways to regulate autophagy, whereas autophagy induction promotes NRP1 degradation. This bidirectional interplay directly governs tumor progression and therapy resistance. Although prior studies have provided some clues about their interaction, the regulatory network and the precise mechanisms linking NRP1 and autophagy in the TME remain incompletely characterized. Precision therapies targeting the NRP1-autophagy axis still face multiple obstacles. This review synthesizes data from the atlas cancer genome (TCGA), the genotype-tissue expression (GTEx) database, and the human autophagy database (HADb) to explore associations between NRP1 and autophagy-related gene (ATG) in expression and prognosis, elucidate NRP1-autophagy interaction mechanisms and therapeutic opportunities and challenges in targeting the NRP1-autophagy axis. Pan-cancer analysis showed significant upregulation of NRP1 in 10 solid tumor types and revealed co-expression relationships between NRP1 and 340 ATGs. Among these, co-expression patterns involving genes such as CXCR4 and HSPA5 had significant prognostic value in gastric cancer and glioblastoma. This review systematically explores the panoramic regulatory framework of the NRP1-autophagy axis in the tumor immune microenvironment through bidirectional regulation of activating immunity and inhibitory immunity at the pan-cancer level. It fills the gap in the systematic summary of the NRP1-autophagy axis in regulating the dynamics of the tumor immune microenvironment, and provides a theoretical basis for the clinical translation of combination chemotherapy and immunotherapy targeting the NRP1-autophagy axis.

Background: Hepatoid adenocarcinoma of the stomach (HAS) is a rare subtype of gastric cancer (GC) characterized by alpha-fetoprotein (AFP) production and invasive liver and lymph node metastases, typically associated with a poor prognosis. Although immuno-chemotherapy has made significant achievements in the conversion therapy of advanced GC in recent years, the management of HER2-negative, proficient mismatch repair (pMMR), and a programmed cell death ligand-1 (PD-L1) combined positive score (CPS)<5 cases, particularly in the context of synchronous multiple liver metastases and lymph node involvement, poses significant challenges. This is attributable not only to its rapid progression but also to its poor prognosis. We retrospectively report a case of HAS with concurrent multiple liver and lymph node metastases. Following six cycles of immuno-chemotherapy, R0 resection was achieved, and postoperative pathological examination confirmed a pathological complete response (pCR). No recurrence or metastasis was observed at the 32-month postoperative follow-up (last follow-up: April 26, 2025). To our knowledge, no previous reports have documented pCR in HER2-negative, pMMR, and PD-L1 CPS<5 patients with advanced HAS following conversion therapy with combined immuno-chemotherapy. This report aims to provide further clinical reference for the treatment of advanced HAS.Case summary: A 51-year-old male patient was diagnosed with HAS accompanied by multiple liver and lymph node metastases. Following six cycles of immunotherapy (sintilimab) combined with chemotherapy (Nab-paclitaxel, oxaliplatin, and S-1), the primary tumor exhibited significant reduction. Multiple liver metastases showed partial shrinkage or disappearance (the target lesion diameter must be less than 10 mm), and retroperitoneal lymph nodes were no longer detectable. After thorough evaluation, R0 resection was deemed achievable. Therefore, radical distal gastrectomy with D2 lymphadenectomy and liver metastasectomy were performed. Postoperative pathology confirmed pCR. The patient has remained progression-free survival (PFS) for 32 months and overall survival (OS) for 38 months, with no evidence of recurrence or metastasis.Conclusion: HAS is a highly invasive malignant tumor of the stomach. The dynamic changes in AFP serve as a reliable indicator for detecting HAS, evaluating treatment efficacy, and predicting recurrence. In advanced HER-2-negative, PD-L1 CPS<5, pMMR-type HAS, employing a conversion therapy regimen combining sintilimab with Nab-paclitaxel, oxaliplatin, and S-1 may reduce tumor staging, enhance conversion therapy success rates, and prolong survival.

BACKGROUND Pancreatic cancer (PC) remains one of the most aggressive malignancies, is characterized by rapid progression and high metastatic potential, and is the fourth leading cause of cancer-related mortality worldwide. The incidence and mortality rates of PC continue to rise annually. Despite advances in imaging technologies and treatment strategies over the past two decades, the 5-year survival rate for patients with PC remains low, at approximately 13%. Patients with advanced PC still experience dismal outcomes, primarily due to the tumor's aggressiveness and high metastatic capacity. Thus, there is an urgent need to identify reliable molecular biomarkers and therapeutic targets to improve the prognosis of patients with PC. AIM To investigate the biological functions and mechanisms of DEAD/H-box RNA helicase 10 (DDX10) in PC progression. METHODS We comprehensively investigated the expression pattern and functional significance of DDX10 in PC using a multi-omics integrative approach. We performed bioinformatics analyses of datasets from The Cancer Genome Atlas and Gene Expression Omnibus, tissue microarray-based immunohistochemistry, and a series of in vitro functional assays to assess cellular proliferation, migration, invasion, and apoptosis. Additionally, transcriptomic and proteomic analyses were integrated to delineate the molecular regulatory networks that mediate the aggressive phenotype of PC. RESULTS DDX10 was found to be significantly overexpressed at both the mRNA and protein levels in PC tissues compared with adjacent non-tumor tissues. Silencing DDX10 in vitro led to marked inhibition of PC cell proliferation, migration, and invasion, accompanied by enhanced apoptosis. Integrated RNA sequencing, proteomic profiling, and western blot validation revealed that DDX10 modulates key oncogenes including RRM2, LIG1, CDK6, and ITGA2. Notably, ectopic RRM2 overexpression partially rescued the growth-suppressive effects induced by DDX10 knockdown in PANC-1 cells, and high DDX10 expression is associated with poor overall survival in patients with PC. CONCLUSION Collectively, our findings indicate that DDX10 promotes PC cell proliferation primarily by upregulating RRM2, thus highlighting its potential as a promising therapeutic target in PC.

Immune checkpoint blockade (ICB) has made great progress in treating cancer, regulating the tumor immune microenvironment can improve the efficacy of ICB and has become a major focus. Pyroptosis, as a new form of cell death, has been reported in a few diseases to activate cellular immune responses due to the release of inflammatory factors. This may offer a new approach for regulating the tumor immune microenvironment. MT1JP plays an important role in gastric cancer, but its mechanism of pyroptosis and immunity is unclear. Bioinformatics analysis combined with qRT-PCR revealed the expression levels of MT1JP and miR-103a-3p in GC cells and tissues, and their interactions were revealed by dual-luciferase assay and rescue experiment. The effects of MT1JP on GC cell proliferation, invasion, and migration were assessed by CCK-8, EdU, Colony formation, Wound healing, and Transwell. Western blot, IHC, IF, and ELISA were used to assess the effects of MT1JP/miR-103a-3p in GC cell pyroptosis and immunity. MT1JP expression was downregulated and miR-103a-3p was upregulated in GC cells and tissues, the expression of MPDZ was downregulated in AGS and MKN-45. Overexpression of MT1JP inhibited GC cell proliferation, invasion, and migration. MT1JP directly targets and inhibits miR-103a-3p. MT1JP/miR-103a-3p induced the expression of pyroptosis-related proteins (GSDMD, NLRP3, Caspase1) and inflammatory factors (IL-1β, IL-18), activated the immune pathway Sting/IFN-β, and downregulated PD-L1. Based on bioinformatics analysis and preliminary exploration in this study, MPDZ may be a potential downstream target of miR-103a-3p. MT1JP/miR-103a-3p can induce pyroptosis, activate the immune response, and then inhibited the growth of gastric cancer, possibly acting through MPDZ. This explored a new anti-cancer method to regulate the tumor immune microenvironment.

BACKGROUND Pancreatic cancer (PC) remains one of the most lethal malignancies. While flap endonuclease-1 (FEN1) has been implicated in various cancers, its role in PC remains unclear. AIM To investigate the biological functions and mechanisms of FEN1 in PC progression. METHODS FEN1 expression and its prognostic significance were analyzed using Gene Expression Omnibus, The Cancer Genome Atlas, and Genotype-Tissue Expression databases. FEN1 was knocked down or overexpressed in PC cell lines using lentiviral vectors. Cell proliferation, migration, and invasion were assessed in vitro , while tumorigenicity was evaluated in nude mouse xenografts. Molecular mechanisms were explored through RNA-sequencing and validated by western blot analysis. RESULTS FEN1 was significantly upregulated in PC tissues and correlated with poor prognosis. FEN1 promoted PC cell proliferation, migration, and invasion in vitro , as well as xenograft tumor growth in vivo . Mechanistically, FEN1 regulated epithelial-mesenchymal transition through the AKT/mTOR signaling pathway. CONCLUSION FEN1 functions as an oncogenic driver in PC progression via the AKT/mTOR signaling pathway, suggesting its potential as a therapeutic target.

Gastric cancer is a significant contributor to worldwide cancer deaths with limited treatment options and poor patient survival. MicroRNAs play crucial roles as potential oncogenic factors or tumor suppressors in cancers by modulating cell cycle progression, proliferation, migration, invasion, and apoptosis. However, the functional implications of miR-103a-3p in gastric cancer remain poorly known. The current study demonstrates a noteworthy increase in the expression of miR-103a-3p in gastric cancer tissues when compared to neighboring non-cancerous tissues. Our functional investigations indicate that the upregulation of miR-103a-3p contributes to enhanced proliferation, invasion, and migration capabilities in gastric cancer cells. After mechanistic studies, our findings indicate that miR-103a-3p may directly target insulin-like growth factor binding protein 5 (IGFBP5) in gastric cancer. Moreover, rescue experiments reveal that IGFBP5 overexpression can attenuate the progression induced by miR-103a-3p in gastric cancer cells. In summary, our findings suggest that the miR-103a-3p/IGFBP5 axis may play a role in gastric cancer progression, highlighting its potential as a therapeutic target and prognostic marker.

Background N-acetyltransferase 10 (NAT10) is involved in several cellular processes. NAT10 expression is essential for the promotion of mRNA translation and stability. In some situations, deregulation of NAT10 has been attributed to the development of multiple types of cancer. NAT10 is significantly upregulated in various gastrointestinal tumors, including esophageal, colorectal, pancreatic, and liver cancers, and is correlated with poor prognosis. Additionally, NAT10 expression contributes to chemotherapy resistance in both esophageal and colorectal cancers. Nevertheless, the role of NAT10 in gastric cancer (GC), a type of gastrointestinal tumor, is not fully understood. Methods Throughout this investigation, our team evaluated NAT10 expression levels in GC patient samples and databases available to the general public. Based on the knockdown and overexpression of NAT10, in vitro experiments were conducted to examine the effects of NAT10 on GC progression and resistance to chemotherapy. Results Our study demonstrated that GC tissues exhibit increased levels of NAT10. Downregulation of NAT10 decreased GC cell proliferation, migration, and invasiveness. Conversely, upregulation of NAT10 resulted in the opposite effect. Furthermore, NAT10 fosters the progression of GC cells by activating the Wnt/β-catenin signaling pathway. NAT10 also promotes resistance to cisplatin chemotherapy. Conclusions Our findings indicated that expression of NAT10 promoted GC progression through activation of the Wnt/β-catenin signaling pathway. We investigated the effect of NAT10 on the viability of GC cells treated with different doses of cisplatin. The results showed that NAT10 expression could impact the effectiveness of chemotherapy resistance in GC. This implies that using NAT10 as a target may be a potential therapeutic strategy for treating GC.