bims-netuvo Biomed News
on Nerves in tumours of visceral organs
Issue of 2025–09–21
eight papers selected by
Maksym V. Kopanitsa, Charles River Laboratories
  1. Wired for growth: neuron-tumour signalling in the lung and brain increases growth of a hard-to-treat cancer.
  2. Perineural invasion affects the risk and pattern of recurrence in non-small cell lung cancer.
  3. MRI-fusion biopsy era: the role of perineural invasion in low-risk prostate cancer.
  4. RBMS1-mediates the biogenesis of circNFIB promotes perineural invasion of pancreatic ductal adenocarcinoma via the L1CAM/MAPK pathway.
  5. Pretreatment intravoxel incoherent motion histogram metrics and clinical characteristics for prediction of perineural invasion status and survival in patients with rectal cancer.
  6. Potential impact of omentin-1 genetic variants on perineural invasion in prostate cancer.
  7. Cancer pain experiences in adult patients with cancer: A qualitative meta-ethnography.
  8. Pharmacological interventions targeting β-adrenoceptors in colorectal cancer: an evolving paradigm.
  1. Nature. 2025 Sep 17.
    Wired for growth: neuron-tumour signalling in the lung and brain increases growth of a hard-to-treat cancer.
    Abbie S Ireland, Trudy G Oliver.
      
    Keywords:  Cancer; Medical research; Neuroscience
    DOI:  https://doi.org/10.1038/d41586-025-02705-5
  2. Eur J Cardiothorac Surg. 2025 Sep 19. pii: ezaf299. [Epub ahead of print]
    Perineural invasion affects the risk and pattern of recurrence in non-small cell lung cancer.
    Beatrice Chia-Hui Shih, Woohyun Jung, Jeong Hoon Lee, Sukki Cho, Jae Hyun Jeon, Jin-Haeng Chung, Kwhanmien Kim, Sanghoon Jheon.
       OBJECTIVES: We evaluated the impact of perineural invasion on recurrence risk and patterns in patients with non-small-cell lung cancer.
    METHODS: We retrospectively analyzed 5,545 patients who underwent curative resection for pathologic stage I-III non-small-cell lung cancer between 2009 and 2021. Perineural invasion was defined as the presence of tumour cells within nerve sheath layers or tumour foci involving ≥33% of the nerve's circumference. After stratifying patients by perineural invasion status, we compared recurrence-free survival and recurrence patterns.
    RESULTS: Perineural invasion was identified in 290 patients (5.3%), with prevalence increasing by stage (1.8%, 11.6%, and 18.7% in stage I, II, and III, respectively). The perineural invasion (+) group included higher proportions of males and smokers, had lower pulmonary function, higher SUVmax, more advanced pathological stage, and increased prevalence of squamous cell carcinoma and other pathologic invasiveness markers. The cumulative incidence of recurrence was significantly higher in the presence of perineural invasion (5-year cumulative incidence: 42.4% in the perineural invasion (+) group vs 16.5% in the perineural invasion (-) group; Gray's test, p < 0.001). Stage-stratified multivariable analysis demonstrated that perineural invasion increased recurrence risk in stages I-II (p < 0.001 and p = 0.021, respectively), but not in stage III (p = 0.245). This trend was consistent in the interaction analysis (p < 0.001). In the recurrence pattern analysis, extrathoracic recurrence was more frequent when perineural invasion was present (p = 0.002).
    CONCLUSIONS: Perineural invasion is associated with an increased risk of recurrence in NSCLC, particularly in early-stage disease. When perineural invasion is present, extrathoracic recurrence is observed more frequently.
    Keywords:  non-small cell lung cancer; perineural invasion; recurrence
    DOI:  https://doi.org/10.1093/ejcts/ezaf299
  3. Curr Probl Cancer. 2025 Sep 13. pii: S0147-0272(25)00078-9. [Epub ahead of print]59 101251
    MRI-fusion biopsy era: the role of perineural invasion in low-risk prostate cancer.
    Nethusan Sivanesan, Gabriela M Diaz, Sebastien Strachan, Keervani Kandala, Xiwen Zhao, Wei Shen Tan, Michael S Leapman, Preston C Sprenkle.
       OBJECTIVE: To evaluate whether perineural invasion independently predicts Gleason score upgrading during active surveillance in patients undergoing MRI-US fusion biopsy.
    PATIENTS AND METHODS: We retrospectively analyzed 325 patients initially diagnosed with Gleason Grade Group (GGG) 1 prostate cancer who underwent at least one subsequent biopsy. Demographics, imaging, and clinical variables were recorded. Univariate and multivariate logistic regression models assessed the association between perineural invasion and Gleason upgrading (GGG2+) on follow-up biopsy.
    RESULTS: Among 325 eligible patients diagnosed with GGG 1 prostate cancer on initial biopsy, 51 (15%) had perineural invasion, while 274 (84%) did not. Gleason upgrade occurred in 110 (34%) patients. Upgrading was observed in 24 of 51 patients (47%) with perineural invasion, compared to 86 of 274 patients (32%) without perineural invasion (p = 0.03). On univariate analysis, older age (OR 1.03; p=0.03), African American race (OR 2.22; p=0.04), number of positive cores (OR 1.13; p=0.007), and cancer detected on targeted biopsy (OR 2.26; p=0.01) were associated with upgrading. In multivariable analysis, perineural invasion (OR 1.84; p=0.1) was not independently associated with Gleason upgrading when adjusting for PI-RADS 4-5 (OR 1.98; p=0.01). However, cancer detected on targeted biopsy (OR 2.26; p = 0.01) and African American race (OR 3.2; p = 0.01) remained independently associated with upgrading.
    CONCLUSIONS: In this contemporary series of patients managed with active surveillance in the era of MRI-ultrasound fusion biopsy, perineural invasion is not associated with Gleason upgrade on subsequent biopsy when adjusting for MRI- US fusion biopsy characteristics. Our findings highlight that a PI-RADS 4 or 5 lesion, and cancer found within an MRI-visible lesion are more predictive of subsequent progression in patients with GGG1 PCa.
    Keywords:  Active surveillance; Gleason grading; Perineural invasion; Prostate cancer; Risk
    DOI:  https://doi.org/10.1016/j.currproblcancer.2025.101251
  4. Theranostics. 2025 ;15(17): 9261-9278
    RBMS1-mediates the biogenesis of circNFIB promotes perineural invasion of pancreatic ductal adenocarcinoma via the L1CAM/MAPK pathway.
    Zhuo Wu, Zhou Fang, Liangtang Zeng, Dingwen Zhang, Yu Zhou, Rufu Chen.
      Background: Circular RNAs (circRNAs) play a key regulatory role in various functional characteristics of pancreatic ductal adenocarcinoma (PDAC). However, the mechanisms underlying circRNA's involvement in the occurrence of perineural invasion (PNI) in PDAC remain unclear and require further investigation. Methods: Through circRNA sequencing, we identified the circNFIB (hsa_circ_0086376) that is highly associated with PNI in PDAC tissues. We then evaluated the promoting effect of circNFIB on PNI using various assays, including the Matrigel/dorsal root ganglia (DRG) model, DRG-matrix assay, transwell assay, orthotopic xenograft model, and in vivo model of neural infiltration. The interaction mechanism between circNFIB and IGF2BP3, which enhances L1CAM mRNA stability, was explored using RNA pulldown, mass spectrometry, RNA Immunoprecipitation (RIP), and actinomycin D assays. Additionally, the role of RBMS1 in promoting the biogenesis of circNFIB was investigated using RIP and Western blotting. Results: This study confirmed that circNFIB is significantly upregulated in PDAC samples and samples with high PNI. Both in vitro and in vivo experiments demonstrated its role in promoting PNI in PDAC. Mechanistically, circNFIB binds with IGF2BP3 in PDAC cells to enhance the stability of L1CAM mRNA, activating the ERK/MAPK signaling pathway, and facilitating PNI in PDAC. Additionally, we found that RBMS1 binds to the NFIB pre-mRNA and promotes the biogenesis of circNFIB. Finally, we verified circNFIB as a potential therapeutic target that can mitigate the anti-tumor effects of SCH772984 in vivo. Conclusion: RBMS1-mediated circNFIB interacts with IGF2BP3 to stabilize L1CAM mRNA, thereby activating the ERK/MAPK signaling pathway and promoting PNI in PDAC. This study provides a novel perspective on the molecular mechanisms underlying PNI in PDAC and lays the theoretical foundation for circNFIB as a potential therapeutic target for PDAC.
    Keywords:  L1CAM; RBMS1; circNFIB; pancreatic ductal adenocarcinoma; perineural invasion
    DOI:  https://doi.org/10.7150/thno.112753
  5. Insights Imaging. 2025 Sep 19. 16(1): 199
    Pretreatment intravoxel incoherent motion histogram metrics and clinical characteristics for prediction of perineural invasion status and survival in patients with rectal cancer.
    Ao Yang, Hao Xu, Xin Zhang, Ping Zheng, Li Bo Lin, Jie Ke Liu, Peng Zhou, Xiao Li Chen.
       OBJECTIVES: To explore intravoxel incoherent motion (IVIM) for evaluation of the perineural invasion (PNI) status and survival in patients with rectal cancer.
    MATERIALS AND METHODS: The true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and microvascular volume fraction (f) were recorded together with histogram metrics. Differences in IVIM histogram metrics between the PNI-positive group and the PNI-negative group were analyzed. Univariable and multivariable logistic regression analysis were used for model construction. The area under the receiver operating characteristic curve (AUC) was used to assess the diagnostic performance of the models. Histopathology was used as the PNI endpoint. Kaplan-Meier curve analysis was employed to estimate the disease-free survival (DFS) and overall survival (OS) of patients.
    RESULTS: A total of 175 patients were retrospectively enrolled in this study. Multivariable logistic regression analysis showed that higher D_median (odds ratio (OR) = 2.036, p = 0.003) and D_min (OR = 1.479, p = 0.002) and lower f_SD (OR = 0.697, p < 0.001) and f_kurtosis (OR = 0.485, p < 0.001) were independently associated with PNI-positive. The combined model showed the best performance in predicting the PNI status with AUCs, sensitivity, specificity, and accuracy of 0.885, 81.67%, 82.61%, and 82.29%, respectively. Kaplan-Meier curves analysis revealed that the patients with higher scores (> -1.12) of the combined model showed relatively lower 2-year DFS (81.6% vs 93.2%, p = 0.014) compared to the patients with lower scores (≤ -1.12).
    CONCLUSION: IVIM histogram metrics could predict the PNI status and serve as a preoperative risk stratification tool.
    CRITICAL RELEVANCE STATEMENT: The combination of IVIM histogram metrics and clinical characteristics could discriminate the PNI status and serve as a surrogate for PNI.
    KEY POINTS: The PNI is an important prognostic factor in rectal cancer. The IVIM histogram metrics were associated with the PNI status. The combination of IVIM and clinical factors could serve as a surrogate for PNI.
    Keywords:  Intravoxel incoherent motion; Perineural invasion; Rectal cancer; Survival analysis
    DOI:  https://doi.org/10.1186/s13244-025-02075-6
  6. J Cancer. 2025 ;16(12): 3767-3774
    Potential impact of omentin-1 genetic variants on perineural invasion in prostate cancer.
    Wei-Chun Weng, Tien-Huang Lin, Xiu-Yuan He, Chia-Yen Lin, Hsi-Chin Wu, Yuan-Li Huang, Chao-Yang Lai, Chun-Hao Tsai, Yi-Chin Fong, Shun-Fa Yang, Chih-Hsin Tang.
      One of the most prevalent cancers and a major global cause of mortality in men is prostate cancer (PCa). Omentin-1, an adipokine, has been shown to play a protective role by reducing proinflammatory cytokine secretion. The relationships among carcinogenic lifestyle factors, biochemical recurrence (BCR), OMNT1 polymorphisms, and PCa remain unclear. We investigated the impact of clinicopathological features and four OMNT1 gene variants on PCa risk in 701 Taiwanese male patients with and without BCR. Compared with the TT genotype, the TA+AA genotypes of SNP rs2274907 were associated with a lower risk of perineural invasion. Similarly, the AG+GG genotypes of rs4656959 were associated with a lower risk of perineural invasion compared to the AA genotype. Importantly, PCa patients without BCR exhibited the same effects. Interestingly, the wild-type TT homozygous genotype was associated with significantly lower OMNT1 expression levels compared to the AA genotype of the rs2274907 variant. Additionally, OMNT1 mRNA levels were lower in PCa tissues compared to normal tissues, indicating that omentin-1 acts as a protective factor in PCa.
    Keywords:  genetic polymorphisms; omentin-1; prostate cancer
    DOI:  https://doi.org/10.7150/jca.119089
  7. Eur J Oncol Nurs. 2025 Sep 08. pii: S1462-3889(25)00202-9. [Epub ahead of print]78 102978
    Cancer pain experiences in adult patients with cancer: A qualitative meta-ethnography.
    Younhee Jeong, YeoJin Im, Hyungran Lee, YoungAh Park.
       PURPOSE: Cancer pain is a major symptom that significantly affects patients' quality of life and overall well-being. An integrated understanding of the multidimensional aspects of cancer pain based on patients' lived experiences is necessary prior to pain management. The purpose of this meta-synthesis is to systematically compile and interpret qualitative research on cancer pain, thereby providing a synthesized understanding of the challenges and nuances of pain as experienced by adult patients with cancer.
    METHOD: A qualitative meta-synthesis was conducted using seven phases of meta-ethnography. A comprehensive search across seven databases, culminating in December 2023. Quality appraisal of 22 studies was conducted using the CASP checklist, with data extraction emphasizing participant quotes and primary data for generating new insights through meta-ethnography.
    RESULTS: 122 first codes were identified and classified from the included studies. These findings were aggregated into 40 s codes and subsequently condensed into 13 sub-themes. From these 13 sub-themes, five synthesized themes were developed: 'Intricate Nature with Wide Spectrum of Expressions,' 'Harsh Realities,' 'Destroyer of Myself and My Life,' 'Searching for Freedom from Pain with a Journey of Resilience,' and 'Vitality of Spirituality and Reflection' on the cancer pain experience.
    CONCLUSIONS: This research supports various features of cancer pain experiences encompassing from deteriorating impact on life and positive coping with spirituality and resilience. Changes improve access to comprehensive care services, ensuring that psychosocial and spiritual support, are integral to manage cancer pain. These promise to enhance patient care and foster a more empathetic healthcare environment.
    Keywords:  Cancer pain; Meta-synthesis; Patient experience; Qualitative research
    DOI:  https://doi.org/10.1016/j.ejon.2025.102978
  8. Inflammopharmacology. 2025 Sep 15.
    Pharmacological interventions targeting β-adrenoceptors in colorectal cancer: an evolving paradigm.
    Aya Ghosn, Khalil Bassam, Mohammad Al Zein, Suzanne A Nasser, Gianfranco Pintus, Ali H Eid.
      Colorectal cancer (CRC) is a significant global health challenge, ranking as the third most common cancer and the second leading cause of cancer-related deaths worldwide. Its development is influenced by several risk factors, including smoking, diets rich in red meat, and the effects of stress-related hormones such as epinephrine and norepinephrine. These hormones act through β-adrenergic receptors (β-ARs), which are present on CRC cells and are associated with cancer-promoting processes such as increased cell growth, invasion, blood vessel formation, and accelerated disease progression. Notably, β-ARs blockers have shown potential in slowing CRC progression, pointing to a promising therapeutic strategy. This review explores the main signaling pathways through which β-ARs contribute to cancer development and how various risk factors may influence these mechanisms. We also provide an overview of current preclinical and clinical studies on β-AR blockers in CRC, identify existing gaps in knowledge, and propose directions for future research to optimize therapeutic outcomes.
    Keywords:  COX-2; Chemotherapy; Cyclin; Malignancy; VEGF; microRNA, Adrenergic
    DOI:  https://doi.org/10.1007/s10787-025-01925-5
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