bims-netuvo 2025-03-16 papers

Cancers (Basel). 2025 Mar 01. pii: 852. [Epub ahead of print]17(5):

Spatial Transcriptomics Reveals Novel Mechanisms Involved in Perineural Invasion in Pancreatic Ductal Adenocarcinomas.

Vanessa Lakis, Noni L Chan, Ruth Lyons, Nicola Blackburn, Tam Hong Nguyen, Crystal Chang, Andrew Masel, Nicholas P West, Glen M Boyle, Ann-Marie Patch, Anthony J Gill, Katia Nones.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has a high incidence of perineural invasion (PNI), a pathological feature of the cancer invasion of nerves. PNI is associated with a poor prognosis, local recurrence and cancer pain. It has been suggested that interactions between nerves and the tumor microenvironment (TME) play a role in PDAC tumorigenesis.
METHODS: Here, we used Nanostring GeoMx Digital Spatial Profiler to analyze the whole transcriptome of both cancer and nerve cells in the microenvironment of PNI and non-PNI foci from 13 PDAC patients.
CONCLUSIONS: We identified previously reported pathways involved in PNI, including Axonal Guidance and ROBO-SLIT Signaling. Spatial transcriptomics highlighted the role of PNI foci in influencing the immune landscape of the TME and similarities between PNI and nerve injury response. This study revealed that endocannabinoid and polyamine metabolism may contribute to PNI, cancer growth and cancer pain. Key members of these pathways can be targeted, offering potential novel research avenues for exploring new cancer treatment and/or pain management options in PDAC.

Keywords: MGLL; SAT1; nerve; pain; perineural invasion; spatial transcriptomics

DOI: https://doi.org/10.3390/cancers17050852

Cancer Lett. 2025 Mar 11. pii: S0304-3835(25)00160-0. [Epub ahead of print] 217596

Tumor-derived exosomal LINC01812 induces M2 macrophage polarization to promote perineural invasion in cholangiocarcinoma.

Qinlei Wang, Zhaowei Sun, Jingyun Guo, Haoran Li, Jingru Zhang, Bingyuan Zhang, Bin Zhou, Yujie Feng.

M2 macrophages play a critical role in the tumor microenvironment of invasive solid tumors. They are closely associated with perineural invasion (PNI) and are often linked to poor prognosis. In this context, tumor-derived exosomes serve as important mediators of intercellular communication. However, the relationship between tumor cell-induced M2 macrophages and PNI in cholangiocarcinoma remains unexplored. In this study, we utilized multiplex immunofluorescence and transcriptomic sequencing to demonstrate the upregulation of LINC01812 in cholangiocarcinoma tissues and its positive correlation with M2 macrophage infiltration. Exosomal lncRNA sequencing, exosome uptake experiments, RNA pull-down assays, and mass spectrometry analysis demonstrated that macrophages can internalize exosomal LINC01812 and promote the M2 phenotype in cholangiocarcinoma cells. Additionally, Transwell and in vitro cocultures with the dorsal root ganglia confirmed that the tumor microenvironment significantly enhances the nerve infiltration of cholangiocarcinoma cells via M2 macrophages. The findings of this study indicate that exosomes containing LINC01812 derived from cholangiocarcinoma can induce M2 macrophage polarization and facilitate nerve infiltration, thereby providing new potential therapeutic targets for managing PNI in cholangiocarcinoma.

Keywords: Crosstalk; Cytokine; Nerve infiltration; Targeted therapies; Tumor metastasis

DOI: https://doi.org/10.1016/j.canlet.2025.217596

Int J Med Sci. 2025 ;22(6): 1269-1277

Genetic variants of IGF2BP2 as potential predictors for perineural invasion of prostate cancer in a Taiwanese population.

Wei-Chun Weng, Yung-Wei Lin, Chung-Howe Lai, Chia-Yen Lin, Yu-Ching Wen, Lun-Ching Chang, Shun-Fa Yang, Ming-Hsien Chien.

Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), which binds with high affinity to numerous RNA transcripts, is known to promote tumorigenesis and metastasis, including in prostate cancer (PCa). Several case-control studies investigated associations between IGF2BP2 polymorphisms and cancer progression. However, the effects of IGF2BP2 genetic variants on clinicopathological progression and biochemical recurrence (BCR) of PCa remain unclear. In this study, we recruited 698 Taiwanese PCa patients who underwent a radical prostatectomy to investigate associations of IGF2BP2 single-nucleotide polymorphisms (SNPs) with the risk of BCR and clinicopathological progression. Using a TaqMan allelic discrimination assay, we genotyped three IGF2BP2 SNPs located in the second intron: rs11705701 (G/A), rs4402960 (G/T), and rs1470579 (A/C). Our findings revealed that these IGF2BP2 SNPs had no significant effect on initial prostate-specific antigen (iPSA) levels or postoperative BCR. However, patients with the rs1470579 A/C genotype exhibited a higher risk of developing perineural invasion (PNI) compared to those with the homozygous A/A genotype. This association was particularly pronounced in patients with an elevated iPSA level (>10 ng/mL). Clinical observations from The Cancer Genome Atlas database showed that elevated IGF2BP2 levels in PCa tissues were significantly associated with higher Gleason scores and exhibited a trend toward correlating with tumor metastasis. In conclusion, our findings highlight that the IGF2BP2 rs1470579 A>C polymorphism may increase susceptibility for PNI among PCa patients in the Taiwanese population.

Keywords: Insulin-like growth factor 2 mRNA-binding protein 2; Perineural invasion; Prostate cancer; Single-nucleotide polymorphism

DOI: https://doi.org/10.7150/ijms.109770

World J Surg Oncol. 2025 Mar 08. 23(1): 79

Evaluation of the details and importance of lymphatic, microvascular, and perineural invasion in patients with non-functioning pancreatic neuroendocrine neoplasms based on tumor size and the 2022 World Health Organization classification: a 23-year retrospective analysis.

Wataru Izumo, Hiromichi Kawaida, Ryo Saito, Yuki Nakata, Hidetake Amemiya, Suguru Maruyama, Koichi Takiguchi, Katsutoshi Shoda, Kensuke Shiraishi, Shinji Furuya, Yoshihiko Kawaguchi, Kunio Mochizuki, Tetsuo Kondo, Daisuke Ichikawa.

BACKGROUND: Although, recently observation methods has been proposed as one of the treatment options for non-functioning pancreatic neuroendocrine neoplasms (NF-PanNENs), determining treatment strategies may be difficult for small and low-malignant NF-PanNENs; thus, clarifying the significance of lymphatic, microvascular, and perineural invasion in these patients is of great clinical importance. This study aimed to assess the incidence and role of lymphatic, microvascular, and perineural invasion in patients with NF-PanNENs based on tumor size and the 2022 World Health Organization classification.
METHODS: From 2000 to 2023, we retrospectively investigated the incidence of lymphatic, microvascular, and perineural invasion and their impact on recurrence in 80 patients who underwent curative resection and were diagnosed with NF-PanNENs.
RESULTS: Of the 80 patients, 14 (18%), 20 (25%), and six (9%) patients had lymphatic, microvascular, and perineural invasion. Patients with neuroendocrine tumor (NET) G1 had significantly fewer occurrences of lymphatic, microvascular, and perineural invasion than those with NET G2 (10%, 15%, and 7% vs. 40%, 55%, and 35%; all P < 0.05.). Patients with a tumor size < 20 mm had significantly lower rates of lymphatic and microvascular invasions than those with a tumor size ≥ 20 mm (12% and 17% vs 33% and 48%; P = 0.034 and 0.0073, respectively). In all patients, NET G2, tumor size ≥ 20 mm, local invasion T2-3, presence of lymph node metastasis, and presence of microvascular invasion were significant risk factors for shorter recurrence-free survival (RFS) (all P < 0.05). In patients with NET G1 and tumor size < 20 mm, five (10%), eight (16%), and four (8%) patients had lymphatic, microvascular, and perineural invasion. The presence of microvascular invasion was also an independent risk factor for RFS (P < 0.05).
CONCLUSIONS: Information on the frequency and role of lymphatic, microvascular, and perineural invasion based on tumor size and malignancy on recurrence may be useful when considering treatment strategies for small- and low-grade NF-PanNENs.

Keywords: Lymphatic invasion; Microvascular invasion; Non-functioning pancreatic neuroendocrine neoplasm; Perineural invasion; Recurrence

DOI: https://doi.org/10.1186/s12957-025-03734-0

Int J Mol Sci. 2025 Mar 05. pii: 2307. [Epub ahead of print]26(5):

Molecular Underpinnings of Brain Metastases.

Maria A Jacome, Qiong Wu, Jianan Chen, Zaynab Sidi Mohamed, Sepideh Mokhtari, Yolanda Piña, Arnold B Etame.

Brain metastases are the most commonly diagnosed type of central nervous system tumor, yet the mechanisms of their occurrence are still widely unknown. Lung cancer, breast cancer, and melanoma are the most common etiologies, but renal and colorectal cancers have also been described as metastasizing to the brain. Regardless of their origin, there are common mechanisms for progression to all types of brain metastases, such as the creation of a suitable tumor microenvironment in the brain, priming of tumor cells, adaptations to survive spreading in lymphatic and blood vessels, and development of mechanisms to penetrate the blood-brain barrier. However, there are complex genetic and molecular interactions that are specific to every type of primary tumor, making the understanding of the metastatic progression of tumors to the brain a challenging field of study. In this review, we aim to summarize current knowledge on the pathophysiology of brain metastases, from specific genetic characteristics of commonly metastatic tumors to the molecular and cellular mechanisms involved in progression to the central nervous system. We also briefly discuss current challenges in targeted therapies for brain metastases and how there is still a gap in knowledge that needs to be overcome to improve patient outcomes.

Keywords: brain metastases; breast cancer; central nervous system; genetic features; lung cancer; melanoma; molecular mechanisms

DOI: https://doi.org/10.3390/ijms26052307