bims-netuvo 2026-01-04 papers

bims-netuvo

Biomed News

on Nerves in tumours of visceral organs

Issue of 2026–01–04
seven papers selected by
Maksym V. Kopanitsa, Charles River Laboratories

Netrin-1 Promotes Pancreatic Tumorigenesis and Innervation through NEO1.
Extracellular Vesicle-Mediated O-GlcNAcase Transfer Drives Neuronal Necroptosis to Facilitate Gallbladder Cancer Perineural Invasion.
Prognostic significance of perineural invasion in salivary duct carcinoma: A systematic review and meta-analysis.
High-Resolution Nerve Ultrasound in Adults with NF1: An Accessible and Reproducible Imaging Tool for Plexiform Neurofibromas.
Pathological features of malignant colorectal polyps: a five-year descriptive retrospective study.
Prediction of brain metastasis in patients with epidermal growth factor receptor-positive lung adenocarcinoma based on lung computed tomography-derived radiomics features.
Risk of central nervous system metastasis and survival in HER2+ positive breast and non-breast cancers.

Cancer Res. 2025 Dec 31.

Netrin-1 Promotes Pancreatic Tumorigenesis and Innervation through NEO1.

Hiroki Kobayashi, Yosuke Ochiai, Junya Arai, Masahiro Hata, Feijing Wu, Masaki Sunagawa, Tadashi Iida, Taisuke Baba, Ermanno Malagola, Takayuki Tanaka, Zhengyu Jiang, Ruth A White, Xiaofei Zhi, Jin Qian, Quin T Waterbury, Ruhong Tu, Biyun Zheng, Yi Zeng, Hualong Zheng, Puran Zhang, Shuang Li, Leah B Zamechek, Jonathan S LaBella, Takahiro Sugie, Atsushi Enomoto, Holger K Eltzschig, Carmine F Palermo, Iok In Christine Chio, Kenneth P Olive, Timothy C Wang.

Nerves can regulate tumorigenesis and cancer progression. However, clarification of the role of axon guidance molecules in tumorigenesis, innervation, and metastasis is required to better understand the tumor-promoting functions of nerves. Using murine KrasG12D-mutant pancreatic organoids, we screened axon guidance molecules and identified netrin-1 upregulation. Netrin-1 was also upregulated in vivo during pancreatic tumorigenesis in humans and mice. Mutant KRAS and β-adrenergic signaling upregulated netrin-1 and its receptor NEO1 in epithelial cells in part through the MAPK pathway. Ex vivo culture of celiac ganglia showed that netrin-1 promoted the axonogenesis of sympathetic neurons through nerve NEO1. In the Pdx1-Cre;LSL-KrasG12D/+ model, knockout of Ntn1, which encodes netrin-1, decreased sympathetic innervation and the development of pancreatic intraepithelial neoplasia. Treatment of pancreatic tumor organoids with recombinant netrin-1 enhanced cell growth, epithelial-mesenchymal transition (EMT), and cancer stemness with the upregulation of ZEB1 and SOX9 through NEO1-mediated activation of focal adhesion kinase (FAK). In Pdx1-Cre;LSL-KrasG12D/+;LSL-Trp53R172H/+ mice, Ntn1 knockout reduced innervation, FAK phosphorylation, and the features of EMT and stemness to extend mouse survival. In a liver metastasis model of pancreatic ductal adenocarcinoma (PDAC), treatment with a netrin-1-neutralizing antibody or tumoral knockout of Neo1 reduced ZEB1 and SOX9 and decreased tumor progression. In contrast, netrin-1 overexpression promoted innervation and the progression of PDAC liver metastasis. These data suggest that the netrin-1/NEO1 axis is a key regulator of PDAC progression, directly influencing cancer cell stemness and EMT, while indirectly promoting tumor growth through nerves. Inhibiting the netrin-1 pathway could represent a potential therapeutic approach for PDAC.

DOI: https://doi.org/10.1158/0008-5472.CAN-25-2243
Cancer Res. 2025 Dec 29.

Extracellular Vesicle-Mediated O-GlcNAcase Transfer Drives Neuronal Necroptosis to Facilitate Gallbladder Cancer Perineural Invasion.

Jing-Wei Zhao, Jia Yun Zhu, Ziyi Yang, Yang-Yang Zhai, Cheng Zhao, Zhichao Lu, Danyang Shen, Qiu-Yi Tang, Xiaoling Song, Lin Jiang, Wen-Ting Dai, Ya-Xuan Wang, Yidi Zhu, Liu-Qing Shi, Runfa Bao, Zhimin Geng, Ziheng Wang, Shi-Lei Liu, Wei Gong.

Peripheral nerve invasion (PNI) is an early and decisive step in gallbladder cancer (GBC) progression that strongly predicts poor post-surgical outcome. The tumor-neuron interactions that drive PNI could represent potential targets and biomarkers to improve treatment of GBC. Here, we demonstrated that GBC provoked necroptosis of neurons to enable PNI. GBC cells transferred extracellular vesicles (EVs) containing O-GlcNAcase (OGA) to neurons, which activated RIPK1-dependent necroptosis. Mechanistically, EV-derived OGA suppressed RIPK1 glycosylation while enhancing its phosphorylation, thereby activating the RIPK1/RIPK3/MLKL axis to trigger neuronal necroptosis. Subsequent neuronal release of HMGB1 engaged RAGE on GBC cells, establishing a loop that accelerated PNI. Moreover, the RAGE antagonist FPS-ZM1 synergized with gemcitabine to suppress tumor progression. Collectively, these findings uncover an EV-mediated crosstalk between GBC cells and neurons in which RIPK1-dependent necroptosis and its effector HMGB1 drive PNI, positioning the HMGB1-RAGE axis as a tractable therapeutic target.

DOI: https://doi.org/10.1158/0008-5472.CAN-25-2237
Crit Rev Oncol Hematol. 2025 Dec 25. pii: S1040-8428(25)00492-5. [Epub ahead of print]218 105104

Prognostic significance of perineural invasion in salivary duct carcinoma: A systematic review and meta-analysis.

Rezhat Abbas, Revathi Krishna, Jeyaseelan Augustine, Priya Kumar, Aadithya B Urs.

  Salivary duct carcinoma is a highly aggressive salivary gland malignancy characterized by rapid progression, early regional and distant metastasis, and poor clinical outcomes. Among the histopathological features associated with its aggressiveness, perineural invasion is of particular significance. Perineural invasion refers to the infiltration of tumor cells within or surrounding the perineural spaces and serves as an important route for tumor dissemination. In salivary duct carcinoma, the presence of perineural invasion has been identified as a negative prognostic indicator, correlating with increased risks of local recurrence, nodal involvement, and distant metastasis. Consequently, evaluation of perineural invasion is crucial in prognostication and treatment planning for patients with salivary duct carcinoma. A systematic review was conducted to evaluate the prevalence of perineural invasion in salivary duct carcinoma and to assess its impact on survival outcomes. Following PRISMA guidelines. PubMed, Scopus, Science direct and Embase were searched up to September, 2025 for studies on salivary duct carcinoma and its prognostic factors. Eligible studies were screened, data extracted, and quality assessed using the QUIPS Scale. Pooled estimates were calculated using a random-effects model. The pooled proportion of perineural invasion among salivary duct carcinoma cases was 0.54 (95 % CI: 0.45-0.63). Meta-analysis using a random-effects model demonstrated that the presence of PNI was significantly associated with poorer survival outcomes (HR = 1.64; 95 % CI: 1.01-2.68). For overall survival, PNI showed a trend towards adverse prognosis (HR = 1.67; 95 % CI: 0.80-3.48), while it emerged as a strong negative predictor for disease-free survival (HR = 3.32; 95 % CI: 1.77-6.23). Similarly, for disease-specific survival (HR = 1.48; 95 % CI: 0.23-9.48), progression-free survival (HR = 2.47), and distant recurrence (HR = 4.56), PNI was consistently associated with unfavorable outcomes, underscoring its role as a significant adverse prognostic factor in salivary duct carcinoma. Its presence is consistently associated with reduced survival and increased recurrence, emphasizing its prognostic importance in patient management.

Keywords:  Head & Neck; Perineural invasion; Prognosis; Salivary duct carcinoma; Survival

DOI:  https://doi.org/10.1016/j.critrevonc.2025.105104
Diagnostics (Basel). 2025 Dec 10. pii: 3146. [Epub ahead of print]15(24):

High-Resolution Nerve Ultrasound in Adults with NF1: An Accessible and Reproducible Imaging Tool for Plexiform Neurofibromas.

D Christine Noordhoek, Koen C van Tulder, Tessa A Ennik, Walter Taal, Judith Drenthen.

  Background/Objectives High-resolution nerve ultrasound (HRUS) is a promising imaging modality in patients with neurofibromatosis type 1 (NF1). The aim of this study was to evaluate the use of HRUS in adults with NF1 by assessing changes in HRUS findings over a two-year follow-up time and reporting interobserver variability. Methods Sixty adult patients with NF1 were invited for a study visit including a clinical examination, nerve conduction studies (NCSs) and HRUS, at baseline and after two-years follow-up. The nerve cross-sectional area (CSA) was measured at standard anatomical sites and at additional sites in cases of nerve enlargements. In 16 patients, the CSA measurements of the median nerve on one side were performed by two observers to assess interobserver variability. Results Fifty-two patients participated in the follow-up visit. During follow-up, 40% of nerve enlargements increased, 46% decreased and 14% remained stable. Especially larger CSA measurements at baseline showed substantial increases and decreases at follow-up. The presence or absence of plexiform neurofibromas remained the same. Interobserver agreement of median nerve CSA measurements with HRUS was 0.982 (95% CI: 0.969-0.99). Conclusions HRUS can be an important additional imaging tool in patients with NF1. It is helpful to distinguish between patients with and without plexiform neurofibromas, which is relevant for estimating the risk of developing malignant peripheral nerve sheath tumors (MPNSTs). The good interobserver agreement supports the use of HRUS in clinical practice. The majority of nerve enlargements decreased spontaneously in size within two years, which limits the reliability of tumor volume as sole marker for treatment response.

Keywords:  NF1; high-resolution nerve ultrasound; nerve conduction studies; neurofibromatosis type 1; plexiform neurofibromas

DOI:  https://doi.org/10.3390/diagnostics15243146
Prz Gastroenterol. 2025 ;20(4): 387-394

Pathological features of malignant colorectal polyps: a five-year descriptive retrospective study.

Tarathep Wongsuriyathai, Wiyada Dankai, Sarawut Kongkarnka, Chanakrit Boonplod, Komson Wannasai.

   Introduction: Malignant polyps are primarily adenocarcinomas arising from adenomatous polyps, with the potential to metastasize to regional lymph nodes and distant sites. In our institute, significant gaps in knowledge about the histopathological characteristics of malignant colorectal polyps continue to exist despite their recent increase in prominence.
Aim: This study aims to describe the demographic and pathological features of malignant polyps and investigate the correlation between the Haggitt level and various parameters.
Material and methods: This retrospective study included patients who underwent colonoscopy and polypectomy with the diagnosis of adenocarcinoma arising from an adenomatous polyp between January 2018 and December 2022.
Results: The correlation between the Haggitt level and variables was assessed using the χ2 test. The study included 53 patients with a 2 : 1 male-to-female ratio and a mean age of 66 years. Malignant polyps were primarily located in the sigmoid colon and rectum. The presence of lymphatic and perineural invasion was correlated with a deeper level of invasion.
Conclusions: The rectosigmoid colon is the predilection site for malignant polyps, and a deeper level increases the risk of lymphatic and perineural invasion.

Keywords:  Haggitt levels; adenocarcinomas; lymphatic invasion; malignant polyps; perineural invasion

DOI:  https://doi.org/10.5114/pg.2025.156787
BMC Med Imaging. 2025 Dec 29. 25(1): 511

Prediction of brain metastasis in patients with epidermal growth factor receptor-positive lung adenocarcinoma based on lung computed tomography-derived radiomics features.

Jinhua Zhang, Wei Guo, Lijuan Lin, Xiang Lin, Yang Song, Dairong Cao, Dehua Chen.

   PURPOSE: We investigated lung computed tomography (CT) radiomics features feasibility for brain metastasis (BM) prediction in patients with epidermal growth factor receptor-positive lung adenocarcinoma (LA-EGFRp).
METHODS: Lung CT images and clinical data of patients were retrospectively analyzed. Patients were classified into BM and non-BM groups, and randomly divided into training and test sets (8:2 ratio). Clinical and CT radiomics features were extracted and trained with various machine-learning classifiers to construct the clinical, radiomics, and hybrid models, respectively. Model performance was assessed using receiver operating characteristic curves.
RESULTS: Among 198 included patients, 72 developed BM. Areas under the curve (AUCs) for predicting BM in the training and test sets were 0.781 and 0.701, 0.989 and 0.865, and 0.957 and 0.929 for the clinical, radiomics, and hybrid models, respectively. The AUCs of the radiomics and hybrid models were significantly higher in the training set (P < 0.001) and that of the hybrid model in the test set was higher compared with the clinical model (P < 0.05).
CONCLUSIONS: Models based on clinical data, lung CT-derived radiomics features, and the two combined predicted BM in LA-EGFRp. Combining radiomics and clinical features significantly improved BM prediction, thereby providing an effective tool for clinical decision-making.

Keywords:  Brain metastasis; Epidermal growth factor receptor; Lung adenocarcinoma; Radiomics

DOI:  https://doi.org/10.1186/s12880-025-02059-4
Neurooncol Pract. 2025 Dec;12(6): 1112-1120

Risk of central nervous system metastasis and survival in HER2+ positive breast and non-breast cancers.

Omar Elghawy, John S Wang, Reema Patel, Jack C Shapiro, Shira L Wald, Adam Barsouk, Lauren Reed-Guy, Jessica Xu, Austin Yang, Jonathan H Sussman, Varinder Kaur.

   Background: Incidence, survival, and optimal choice of therapy for central nervous system (CNS) metastasis are well characterized in human epidermal growth factor receptor 2 positive (HER2+) breast cancer (BC), yet remain poorly defined in other HER2+ solid tumors (STs).
Methods: A retrospective cohort analysis was performed to characterize the incidence of CNS metastasis and clinical outcomes in patients with HER2+ breast cancer and ST treated at the University of Virginia Emily Couric Cancer Center between January 2010 and January 2022.
Results: In the cohort, 50 patients had HER2+ ST and 383 had HER2+ BC. Of the ST group, 48.0% received CNS imaging at diagnosis as compared to 2.9% of breast cancer patients (P < .001). Cumulative incidence of CNS metastasis at diagnosis was 4% in the ST vs 1% in the breast cancer cohort (P < .001). Cumulative incidence of CNS metastasis was 20% in ST vs 6.8% in breast cancer cohorts (P < .001). In ST patients with CNS metastasis, 50% received CNS surgery/radiotherapy plus HER2-targeted therapy and 30% received CNS surgery/radiotherapy alone. Overall survival (OS) was significantly poorer in ST (median 1.7 years) vs breast cancer (median 18.5 years) cohorts overall (P < .001), as well as among Stage IV patients (1 year for ST vs 6.3 years for breast cancer).
Conclusions: Patients with non-breast cancer HER2+ STs had higher risk of CNS metastasis and poorer OS compared to HER2+ breast cancer patients, with lower utilization of HER2-directed therapy.

Keywords:  CNS metastasis; HER2+ cancer; breast cancer; radiation oncology

DOI:  https://doi.org/10.1093/nop/npaf057