PDAC is one of the most common malignant tumors worldwide. The difficulty of early diagnosis and lack of effective treatment are the main reasons for its poor prognosis. Therefore, it is urgent to identify novel diagnostic and therapeutic targets for PDAC patients. The m⁷G methylation is a common type of RNA modification that plays a pivotal role in regulating tumor development. However, the correlation between m⁷G regulatory genes and PDAC progression remains unclear. By integrating gene expression and related clinical information of PDAC patients from TCGA and GEO cohorts, m⁷G binding protein NCBP2 was found to be highly expressed in PDAC patients. More importantly, PDAC patients with high NCBP2 expression had a worse prognosis. Stable NCBP2-knockdown and overexpression PDAC cell lines were constructed to further perform in-vitro and in-vivo experiments. NCBP2-knockdown significantly inhibited PDAC cell proliferation, while overexpression of NCBP2 dramatically promoted PDAC cell growth. Mechanistically, NCBP2 enhanced the translation of c-JUN, which in turn activated MEK/ERK signaling to promote PDAC progression. In conclusion, our study reveals that m⁷G reader NCBP2 promotes PDAC progression by activating MEK/ERK pathway, which could serve as a novel therapeutic target for PDAC patients.

The impact of the preoperative carbohydrate antigen 125 (CA125) level on the survival of metastatic colorectal cancer (CRC) patients undergoing primary tumor resection (PTR) remains uncertain. The aim of this study was to assess the prognostic value in overall survival (OS) and cancer-specific survival (CSS) between patients with and without an elevated preoperative CA125 level. All metastatic CRC patients receiving PTR between 2007 and 2017 at the Sixth Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) were retrospectively included. OS and CSS rates were compared between patients with and without elevated preoperative CA125 levels. Among 326 patients examined, 46 (14.1%) exhibited elevated preoperative CA125 levels and the remaining 280 (85.9%) had normal preoperative CA125 levels. Patients with elevated preoperative CA125 levels had lower body mass index, lower preoperative albumin level, lower proportion of preoperative chemotherapy, higher carcinoembryonic antigen and carbohydrate antigen 19–9 (CA19–9) levels, poorer differentiation, and more malignant histopathological type than patients with normal preoperative CA125 levels. In addition, patients with elevated preoperative CA125 levels exhibited more advanced pathological T and N stages, more peritoneal metastasis, and more vessel invasion than patients with normal preoperative CA125 levels. Moreover, the primary tumor was more likely to be located at the colon rather than at the rectum in patients with elevated CA125 levels. Both OS and CSS rates in patients with elevated preoperative CA125 levels were significantly lower than those in patients with normal preoperative CA125 levels. Multivariate Cox regression analysis revealed that an elevated preoperative CA125 level was significantly associated with poor prognosis in metastatic CRC patients undergoing PTR. The hazard ratio (HR) in OS was 2.36 (95% confidence interval [CI], 1.67–3.33, P < 0.001) and the HR in CSS was 2.50 (95% CI, 1.77–3.55, P < 0.001). The survival analysis stratified by peritoneal metastasis also demonstrated that patients with elevated preoperative CA125 levels had lower OS and CSS rates regardless of peritoneal metastasis. Based on an analysis of metastatic CRC patients undergoing PTR, an elevated preoperative CA125 level was associated with poor prognosis, which should be taken into consideration in clinical practice.

Excessive extracellular matrix deposition is a hallmark of intestinal fibrosis in Crohn’s disease (CD), with fibroblasts playing a central pathogenic role. This study aimed to elucidate how macrophages regulate fibroblast activity and contribute to intestinal fibrosis development in CD. Single-cell RNA sequencing (scRNA-seq) data from the Cleveland and MGH cohorts were integrated to identify IL1β⁺ macrophages and PI16⁺ fibroblasts involved in CD-associated fibrosis. Subsequently, above cell–cell interactions were validated by in vitro experiments such as flow cytometry, co-culture assays, ELISA and western blotting. The functional role of amphiregulin (AREG) and its neutralizing antibody AR37 was further assessed in the DSS-induced chronic intestinal fibrosis mice models. PI16⁺ fibroblasts exhibited the highest ECM score, indicating their prominent role in extracellular matrix production. IL1β⁺ macrophages showed the highest pro-fibrotic signature score, suggesting strong pro-fibrotic potential. The ligand–receptor analysis revealed AREG–EGFR interactions between IL1β⁺ macrophages and PI16⁺ fibroblasts. The scRNA-seq data identified IL1β⁺ macrophages as the predominant cellular source of pro-fibrotic factor AREG. Moreover, the in-vitro assays revealed that IL1β⁺ macrophages promoted proliferation and activation of PI16⁺ fibroblasts by secreting AREG. The animal experiment results revealed that AREG neutralizing antibody AR37 attenuated PI16 + fibroblasts expansion and intestinal fibrosis in DSS-induced chronic fibrosis models. IL1β⁺ macrophages promote intestinal fibrosis of CD by increasing proliferation and activation of PI16 + fibroblasts via AREG-EGFR signaling. Targeting the AREG-EGFR signaling could disrupt IL1β⁺ macrophages-PI16⁺ fibroblasts crosstalk to mitigate intestinal fibrosis progression in CD. The online version contains supplementary material available at 10.1186/s12967-026-07969-7. The online version contains supplementary material available at 10.1186/s12967-026-07969-7.

Background: This study aimed to investigate the combined pathological risk factors (PRFs) to stratify low-risk (pT1-3N1) stage III colon cancer (CC), providing a basis for individualized treatment in the future. Patients and methods: PRFs for low-risk stage III CC were identified using COX model. Low-risk stage III CC was risk-grouped combining with PRFs, and survival analysis were performed using Kaplan–Meier. The Surveillance, Epidemiology, and End Results (SEER) databases was used for external validation. Results: Nine hundred sixty-two stage III CC patients were included with 634 (65.9%) as low risk and 328 (34.1%) as high risk. Poor differentiation (OS: P = 0.048; DFS: P = 0.011), perineural invasion (OS: P = 0.003; DFS: P < 0.001) and tumor deposits (OS: P = 0.012; DFS: P = 0.003) were identified as PRFs. The prognosis of low-risk CC combined with 2 PRFs (OS: HR = 3.871, 95%CI, 2.004–7.479, P < 0.001; DFS: HR = 3.479, 95%CI, 2.158–5.610, P < 0.001) or 3 PRFs (OS: HR = 5.915, 95%CI, 1.953–17.420, P = 0.002; DFS: HR = 5.915, 95%CI, 2.623–13.335, P < 0.001) was similar to that of high-risk CC (OS: HR = 3.927, 95%CI, 2.317–6.656, P < 0.001; DFS: HR = 4.132, 95%CI, 2.858–5.974, P < 0.001). In the SEER database, 18,547 CC patients were enrolled with 10,023 (54.0%) as low risk and 8524 (46.0%) as high risk. Low-risk CC combined with 2 PRFs (OS: HR = 1.857, 95%CI, 1.613–2.139, P < 0.001) was similar to that of high-risk CC without PRFs (HR = 1.876, 95%CI, 1.731–2.033, P < 0.001). Conclusion: Combined PRFs improved the risk stratification of low-risk stage III CC, which could reduce the incidence of undertreatment and guide adjuvant chemotherapy.