Background: Pancreatic cancer (PC) is a highly aggressive pancreatic malignant tumor with poor prognosis due to its complex tumor microenvironment (TME) and metastatic potential. Fibroblasts play an important role in tumor progression and metastasis by remodeling the extracellular matrix (ECM) and influencing the immune response. This study explored migrasome-associated fibroblasts, especially TSPAN4 and ITGA5, as key regulators of pancreatic cancer metastasis, aiming to provide new ideas for therapeutic strategies targeting TME.Methods: We employed single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics to analyze pancreatic cancer tissues. Data from the GEO and TCGA databases were integrated and processed using batch correction techniques. Single-cell data were analyzed with Seurat and Monocle for dimensionality reduction and pseudotime trajectory analysis. Cell communication was assessed using CellCall and CellChat. Spatial transcriptomic analysis was conducted with RCTD and MISTy tools to investigate cell interactions within the TME. Additionally, gene enrichment, deconvolution, and prognostic analyses were performed, alongside experimental validation through siRNA transfection, qRT-PCR, and various functional assays to investigate the role of TSPAN4 in metastasis.Results: Our results underscore the critical role of TSPAN4⁺ fibroblasts in pancreatic cancer. These fibroblasts were predominantly located at the tumor periphery and exhibited elevated migrasome gene expression, which was associated with enhanced ECM remodeling and immune suppression. Intercellular communication analysis revealed that TSPAN4⁺ fibroblasts engaged in extensive interactions with immune cells, such as macrophages and endothelial cells, facilitating metastasis and immune evasion. Moreover, the high expression of immune checkpoint markers indicated their involvement in modulating the immune response.Conclusion: TSPAN4⁺ fibroblasts are key regulators of pancreatic cancer progression, contributing to metastasis, immune suppression, and ECM remodeling. Targeting these fibroblasts represents a promising therapeutic strategy to improve clinical outcomes and enhance the effectiveness of immunotherapies in pancreatic cancer.

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Pancreatic ductal adenocarcinoma (PDAC) is characterised by immune hypo‐responsiveness due to its complex, immunosuppressive tumour microenvironment (TME). Mitochondrial metabolic reprogramming allows PDAC cells to shift between glycolysis and oxidative phosphorylation (OXPHOS), supporting energy production and cellular viability, thus promoting tumour progression and therapeutic resistance. Mitochondrial genes associated with PDAC were identified using SMR/HEIDI analysis combined with MRC IEU OpenGWAS and GTEx V8 pancreatic eQTL databases. Single‐cell RNA sequencing (scRNA‐seq) and spatial transcriptomics were used to explore cellular interactions and construct spatial interaction networks. Potential small‐molecule compounds targeting the TME were identified through drug prediction and molecular docking. COA6 expression was silenced in SW1990 and PANC‐1 cells to assess effects on cell proliferation, migration, invasion and apoptosis. COA6, a key gene in the OXPHOS pathway, was upregulated in PDAC tumours compared to normal tissues. Functional assays showed that COA6 overexpression enhanced proliferation, migration and chemoresistance of PDAC cells. COA6 modulates OXPHOS, influences the TME and promotes drug resistance in PDAC. It is a promising therapeutic target for improving clinical outcomes in PDAC patients. Further research is needed to develop COA6‐targeted therapies.

Objectives. To investigate the effects of cytotoxin-associated gene A- (CagA-) positive Helicobacter pylori on proliferation, invasion, autophagy, and expression of miR-125b-5p in colon cancer cells. Methods. Colon cancer cells were cocultured with H. pylori (CagA+) to analyze the effects of H. pylori on miR-125b-5p and autophagy. Colon cancer cells infected with H. pylori (CagA+) were mimicked by transfection of CagA plasmid. The effects of CagA on the proliferation, invasion, and autophagy of colon cancer cells were analyzed. Cell counting kit-8 (CCK-8), clone formation, and Transwell assays were used to detect cell viability, proliferation, and invasion ability, respectively. Proteins and miRNAs were detected by western blotting and qPCR, respectively. Results. H. pylori (CagA+) inhibited expression of miR-125b-5p and promoted autophagy in colon cancer cells. MiR-125b-5p was underexpressed in colon cancer cells after CagA overexpression. CagA promoted colon cancer cell proliferation, invasion, and autophagy. Overexpression of miR-125b-5p inhibited the proliferation, invasion, and autophagy of colon cancer cells and reversed the effects of CagA. Conclusion. H. pylori (CagA+) infection may promote the development and invasion of colon cancer by inhibiting miR-125b-5p.

Background: Ferroptosis is related to the immunosuppression of tumors and plays a critical role in cancer progression. Fanconi anemia complementation group D2 (FANCD2) is a vital gene that regulates ferroptosis. However, the mechanism of action of FANCD2 in Hepatitis B-related hepatocellular carcinoma (HCC) remains unknown. In this study, we investigated the prognostic significance and mechanism of action of FANCD2 in Hepatitis B-related HCC. Methods: The expression of FANCD2 in Hepatitis B-related HCC was explored using The Cancer Genome Atlas (TCGA) and validated using the Gene Expression Omnibus (GEO) database. Univariate and multivariate Cox regression analyses and Kaplan–Meier survival curves were used to analyze the relationship between FANCD2 expression and the overall survival of patients with Hepatitis B-related HCC. Protein–protein interaction networks for FANCD2 were built using the STRING website. In addition, correlations between FANCD2 expression and the dryness index, tumor mutational burden, microsatellite instability (MSI), immune pathways, genes involved in iron metabolism, and sorafenib chemotherapeutic response were analyzed. Results: Our results indicated that FANCD2 was significantly overexpressed in Hepatitis B-related HCC and demonstrated a strong predictive ability for diagnosis (Area Under Curve, 0.903) and prognosis of the disease. High FANCD2 expression was associated with poor prognosis, high-grade tumors, high expression of PDL-1, high MSI scores, and low sorafenib IC50 in Hepatitis B-related HCC. BRCA1, BRCA2, FAN1, and FANCC were vital proteins interacting with FANCD2. The expression level of FANCD2 significantly correlated with the infiltration levels of Treg cells, B cells, CD8 + T cells, CD4 + T cells, neutrophils, macrophages, myeloid dendritic cells, and NK cells in Hepatitis B-related HCC. FANCD2 was positively correlated with the tumor proliferation signature pathway, DNA repair, and cellular response to hypoxia. Conclusion: Our study indicated that FANCD2 was a potential novel biomarker and immunotherapeutic target against Hepatitis B-related HCC, which might be related to the chemotherapeutic response to sorafenib.

OBJECTIVE: The objective of this study was to investigate the impact of the lumbar sagittal profile on pelvic orientation and pelvic motion during postural changes in patients with ankylosing spondylitis (AS) and thoracolumbar kyphosis and to evaluate the potential risk of prosthetic dislocation after total hip arthroplasty (THA) following pedicle subtraction osteotomy (PSO). METHODS: Seventy-two patients with AS-related thoracolumbar kyphosis following spinal osteotomy were retrospectively reviewed, and 21 healthy volunteers were recruited as a control group. Pre- and postoperative 2D full-body images in standing and sitting positions were obtained to evaluate the anterior pelvic plane angle (APPA), lumbar lordosis (LL), sacral slope (SS), pelvic tilt (PT), proximal femur angle (PFA), and femoroacetabular flexion during postural changes. Patients with AS were categorized in either a lordotic or kyphotic group based on the lumbar sagittal profile. RESULTS: Significant increases in the SS and decreases in the APPA, PT, and LL were observed postoperatively in both the standing and sitting positions (p < 0.001 for all). Significantly higher APPA, PT, LL, and ΔPT, and lower SS, ΔSS, and ΔSS+ΔPFA were observed in the kyphotic group (p < 0.05). After undergoing PSO, ΔPT and ΔSS significantly decreased while femoroacetabular flexion significantly increased in both AS groups (p < 0.05), and no significant difference was present between the two groups (p > 0.05). Bath Ankylosing Spondylitis Radiology Hip Index scores in the kyphotic group were significantly worse than those in the lordotic group pre- and postoperatively (p < 0.05). No significant difference in parameters concerning pelvic motion (ΔAPPA, ΔPT, and ΔSS) was found when PSO was performed in the thoracolumbar or lumbar spine. CONCLUSIONS: Lumbar sagittal profiles greatly affect pelvic orientation and pelvic motion in AS. When THA is performed before PSO, AS patients with lumbar kyphosis are at higher risk of anterior prosthetic dislocation, while those with lordotic lumbar sagittal profiles are at higher risk of posterior dislocation. PSO should be performed prior to THA. After PSO, further decreased pelvic motion indicated a potential risk of posterior prosthetic dislocation after sequential THA, whereas theoretically patients with preoperative lumbar kyphosis are at higher risk of THA dislocation. The site where PSO was performed (thoracolumbar or lumbar spine) does not influence the risk of THA dislocation.