bims-netuvo 2025-11-23 papers

bims-netuvo

Biomed News

on Nerves in tumours of visceral organs

Issue of 2025–11–23
seven papers selected by
Maksym V. Kopanitsa, Charles River Laboratories

GRPR-induced FAM135A expression promote perineural invasion in prostate cancer.
Preoperative Diagnostic Value of Spectral CT for Predicting Perineural Invasion in Esophageal Cancer.
Oncological Outcome for 83 Consecutive Patients With Malignant Peripheral Nerve Sheath Tumors Treated at a Tertiary Referral Centre.
Association of LAMA3 expression with perineural invasion and chemoresistance in pancreatic ductal adenocarcinoma.
Characteristic changes in the fusion brain network are associated with bone metastasis pain in patients with lung cancer.
Prognostic Factors and Survival Analysis in Undifferentiated Gastric Carcinoma.
Central Nervous System Progression in Patients Receiving ALK-Targeted Central Nervous System-Penetrable Tyrosine Kinase Inhibitors: Treatment Patterns and Outcomes.

Mol Cancer. 2025 Nov 17. 24(1): 293

GRPR-induced FAM135A expression promote perineural invasion in prostate cancer.

Ning Zhang, Xiaohao Ruan, Siteng Chen, Ruofan Shi, Xiaoqun Yang, Yongle Zhan, Stacia Chun, Chi Yao, Salida Ali, Brian Sze-Ho Ho, Ada Tsui-Lin Ng, Richard Ky Lo, Rong Na.

  Perineural invasion (PNI) is an independent adverse prognostic marker for prostate cancer (PCa) metastasis. Gastrin releasing peptide receptor (GRPR) targeted imaging and therapeutics have entered clinical trials, while its role in PCa perineural invasion remains unclear. Here, we uncovered Family With Sequence Similarity 135 Member A ༈FAM135A༉a dominant PNI driver activated by GRPR in PCa. First, PNI-PCa tissue showed higher neuroactive ligand-receptor interaction activity, and with FAM135A being the most notable marker in PNI group. Then in-vitro experiments using a co-culture system of PCa cells (including AR-positive LNCaP and AR-negative DU145/PC3) showed that FAM135A silencing abrogated tumor malignancy and neural invasion. Moreover, in vivo PCa-Sciatic nerve invasion mouse model demonstrated FAM135A inhibition controls tumor growth and improves motor function. Interestingly, FAM135A is nucleus enriched and its nuclear translocation is mediated by protein cytoplasmic-nuclear transporter RAN. Mechanistically, RNA-Seq and ChIP-Seq analyses identified Teneurin Transmembrane Protein 3 (TENM3) as a transcriptional target of nFAM135A, and TENM3 plays an essential role in nFAM135A-induced cancer-nerve invasion. Notably, FAM135A is ultimately activated by Gastrin Releasing Peptide GRP and its receptor GRPR. Moreover, pharmacological GRPR inhibitor represses FAM135A expression via MED15 activation. Together, we unveil FAM135A as an oncodriver and biomarker of PCa perineural invasion, and provide a novel strategy for PCa innervation therapeutics.

Keywords:  FAM135A; GRPR; Perineural invasion; Prostate cancer; RAN

DOI:  https://doi.org/10.1186/s12943-025-02508-2
Cancer Med. 2025 Nov;14(22): e71403

Preoperative Diagnostic Value of Spectral CT for Predicting Perineural Invasion in Esophageal Cancer.

Zongbo Li, Wenzheng Lu, Yiheng Zhou, Xiaofei Wu, Yuxi Ge, Wei Shao, Shudong Hu.

   PURPOSE: To assess the diagnostic value of preoperative spectral CT quantitative parameters in predicting perineural invasion (PNI) in esophageal squamous cell carcinoma (ESCC), which is a critical prognostic factor associated with increased recurrence and poor survival. Preoperative identification of PNI can guide individualized treatment strategies.
METHODS: A retrospective analysis was conducted on 78 patients with EC who underwent preoperative spectral CT. Patients were classified into PNI-positive and -negative groups on the basis of histopathological findings. Spectral CT parameters, including conventional single-energy CT value (Sect), virtual monochromatic images, effective atomic number (Zeff), and iodine concentration (IC), were compared between groups. Statistical analyses were performed through t, rank sum, and chi-squared tests. A diagnostic nomogram was constructed by employing independent predictors and validated via receiver operating characteristic curve analysis with DeLong's test for the pairwise comparison of the area under the curve (AUC), ensuring the robust evaluation of discriminative performance.
RESULTS: Significant differences in spectral CT parameters were observed between the PNI-positive and PNI-negative groups. Specifically, the PNI-positive group exhibited higher values of 40-70 keV, Zeff, and IC (all p < 0.05) than the PNI-negative group. Among parameters, 40 keV demonstrated the highest predictive accuracy for PNI, with an AUC of 0.943. Binary logistic regression identified CYF, Sect, and 40 keV as independent predictors of PNI status. A nomogram incorporating these variables achieved the optimal diagnostic performance with an AUC of 0.971.
CONCLUSION: Preoperative spectral CT quantitative parameters, particularly 40 keV, Zeff, and IC, provide valuable insights for assessing PNI in ESCC. The integration of spectral CT parameters with clinical features can significantly improve the accuracy of PNI diagnosis.

Keywords:  esophageal cancer; nomogram; perineural invasion; spectral CT

DOI:  https://doi.org/10.1002/cam4.71403
Cancer Rep (Hoboken). 2025 Nov;8(11): e70406

Oncological Outcome for 83 Consecutive Patients With Malignant Peripheral Nerve Sheath Tumors Treated at a Tertiary Referral Centre.

Hannah V M Yeomans, Kira C Lloyd, Felix Haglund de Flon, Sharmineh Mansoori, Panagiotis Tsagkozis, Christina M Linder Stragliotto.

   BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) are rare soft tissue sarcomas with a high risk of recurrence and a poor prognosis, and there is a lack of knowledge regarding long-term follow-up and response to oncological treatment.
AIMS: The aim of this study was to investigate what treatment the patients received and to examine the outcome for patients with MPNST.
METHODS AND RESULTS: This is a retrospective study of patients treated for MPNST at Karolinska University Hospital between 2003 and 2022. Data regarding surgical and oncological treatment and follow-up were collected. Eighty-three patients were identified and included in the study. Tumor grade is available for 72 patients, of which 64 had high-grade tumors. Seventy-nine patients were primarily operated on. Twelve patients presented with distant metastases at diagnosis. Another 37 patients developed local recurrence or distant metastases during follow-up; the median time from surgery to recurrence was 10.5 months (1-95 months, n = 36). The overall mortality rate during the study period was 44% (n = 82). Twenty-seven patients received palliative systemic treatment. The most used therapy for first-line palliative systemic treatment was doxorubicin and ifosfamide. The disease control rate for first-line treatment was 33% (n = 21). The mean overall survival for the cohort was 132 months (95% CI 107-157 months).
CONCLUSION: Forty-five percent of the patients in this material were diagnosed with recurrent disease and most patients treated with palliative systemic therapy experienced brief disease control following treatment. Among patients with MPNST treated with first-line palliative oncological treatment, doxorubicin and ifosfamide have the highest disease control rates. The study also identified a few patients with long-term treatment responses, with four patients alive more than 2 years after starting palliative oncological treatment.

Keywords:  MPNST; neurofibromatosis type 1; oncological treatment; soft tissue sarcoma

DOI:  https://doi.org/10.1002/cnr2.70406
Discov Oncol. 2025 Nov 20.

Association of LAMA3 expression with perineural invasion and chemoresistance in pancreatic ductal adenocarcinoma.

Yang Yang, Yongqiang Chen, Xiaohong Wang, Qikai Sun, Yeben Qian.

   BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a common type of malignant tumor of the pancreas with high aggressiveness and low prognosis. Due to the insidious early symptoms of pancreatic adenocarcinoma, patients are mostly diagnosed at advanced stages with a high incidence of nerve invasion. With the rapid development of precision medicine, studying the molecular mechanisms behind PDAC can help its diagnosis and treatment, which is conducive to improving the prognosis of PDAC patients.
OBJECTIVE: To explore the correlation between LAMA3 expression and nerve invasion in pancreatic ductal adenocarcinoma tissues.
METHODS: Ninety-four patients with pathologically confirmed diagnosis of PDAC in the Department of Hepatobiliary and Pancreatic Surgery of the First Affiliated Hospital of Anhui Medical University were retrospectively collected from January 2023 to December 2023, and the patients' clinicopathological data were collected and followed up for 5 months. Immunohistochemical staining was applied to detect the expression level of LAMA3 in cancer tissues, and paraneoplastic tissues were used as controls to compare the differences in the expression level of LAMA3. The Kaplan-Meier method was used to draw the survival curves, and the Cox proportional risk regression model was set up to analyze the correlation between the expression of LAMA3 and the nerve invasion.
RESULTS: Immunohistochemical staining results showed that LAMA3 was mainly expressed in the cytoplasm and appeared as yellow to brown granules.The positive expression rate of LAMA3 in PDAC cancer tissues was 63.83% (60/94), which was significantly higher than that in paracancerous tissues (12.77%, 12/84), and the difference between the two groups was statistically significant (x2 = 51.862, P < 0.001). Patients were categorized into nerve invasion negative (n = 30) and nerve invasion positive (n = 64) according to the presence or absence of nerve invasion.Cox proportional analysis regression results showed that the LAMA3 expression level was an independent risk factor affecting the occurrence of nerve invasion in PDAC patients. Survival analysis showed that median OS was significantly lower in patients with high LAMA3 expression and development of vascular invasion than in patients with low LAMA3 expression and no vascular invasion (P < 0.001); in TNM staging, median OS was significantly lower in patients with stage II than in patients with stage I (P < 0.001).
CONCLUSION: LAMA3 expression level is an independent risk factor for the occurrence of neuroinvasion in PDAC patients; LAMA3 expression level, TNM staging and prognosis of PDAC patients are correlated; LAMA3 expression level may serve as a valuable biomarker for the occurrence, development, and prediction of prognosis of patients with PDAC, and also as a potential therapeutic target for PDAC patients.

Keywords:  LAMA3; Nerve invasion; Pancreatic ductal adenocarcinoma

DOI:  https://doi.org/10.1007/s12672-025-03971-5
Brain Res Bull. 2025 Nov 14. pii: S0361-9230(25)00451-4. [Epub ahead of print]233 111639

Characteristic changes in the fusion brain network are associated with bone metastasis pain in patients with lung cancer.

Jiahui Zheng, Lin Tang, Xiaoyu Zhou, Yu Tang, Yong Tan, Hong Yu, Jiuquan Zhang, Daihong Liu.

   BACKGROUND: Network neuroscience has revealed characteristic alterations associated with cancer pain in structural and functional brain networks. However, the mechanisms by which structural and functional networks interact and whether the interaction is related to cancer pain remain unclear.
METHODS: First, fusion brain networks were constructed based on structural and functional networks using an optimized self-attention mechanism algorithm. Next, the connectivity strength was analyzed at both regional and modular levels using network-based statistic (NBS) analysis and network connectivity analysis, respectively. Finally, relationships between connectivity strength and neuropsychological scales scores were evaluated.
RESULTS: NBS analysis demonstrated increased connectivities in both BMP+ and BMP- patients, spanning a wide range of brain regions. Additionally, four decreased connectivities were observed in BMP+ patients, involving the default mode network, limbic system, executive control network, and salience network. Network connectivity analysis demonstrated increased connectivity strengths in the feeder network in BMP- patients. Moreover, significant positive correlations were found between altered connectivity strength and neuropsychological scales scores.
CONCLUSIONS: Characteristic changes in the fusion brain network were observed at both regional and modular levels in BMP+ patients, particularly in brain regions related to the descending modulation of cancer pain. Thus, abnormal brain fusion may contribute to cancer pain progression.

Keywords:  Bone metastasis pain; Diffusion spectrum imaging; Fusion brain networks; Lung cancer; Resting-state functional magnetic resonance imaging

DOI:  https://doi.org/10.1016/j.brainresbull.2025.111639
J Clin Pract Res. 2024 Nov;46(6): 537-541

Prognostic Factors and Survival Analysis in Undifferentiated Gastric Carcinoma.

Sedat Carkit, Mustafa Karaagac.

   Objective: Gastric cancer, with notable regional variations in incidence rates, ranks as the third most prevalent cause of cancer-related deaths globally and the fifth most common cancer overall. The objective of this study is to examine the pathological, clinical, and demographic characteristics of patients diagnosed with undifferentiated gastric cancer (UGC) and to determine the major prognostic markers that impact survival and recurrence.
Materials and Methods: This retrospective analysis included patients who underwent surgery for gastric cancer at our center between March 2010 and February 2019. The inclusion criteria required a confirmed diagnosis of UGC and availability of pathological data. Data collected included demographic information, clinical parameters, pathological findings, surgical details, and survival outcomes. The primary outcomes were overall survival and local recurrence.
Results: Twenty-four patients were included, 66.7% of whom were male, with a mean age of 58.5 years. Local recurrence occurred in 50% of patients and was significantly associated with perineural and vascular invasion. Receiver operating characteristic (ROC) analysis identified a metastatic lymph node cutoff of 8.5, with an area under the curve (AUC) of 0.826, specificity of 100%, and sensitivity of 63.2%. Patients with fewer than 8.5 metastatic lymph nodes had a median survival of 16.0 months, compared to 7.0 months for those with more than 8.5 nodes (p=0.003).
Conclusion: Perineural and vascular invasion significantly affect local recurrence in UGC patients. A metastatic lymph node cutoff of 8.5 is a critical predictor of mortality. These findings underscore the importance of thorough pathological assessments and lymph node evaluations in guiding treatment decisions and improving outcomes. Further research is necessary to validate these results and explore additional prognostic markers.

Keywords:  Gastric carcinoma; mortality; prognostic factors; survey; undifferentiated carcinoma

DOI:  https://doi.org/10.14744/cpr.2024.85667
JTO Clin Res Rep. 2025 Dec;6(12): 100914

Central Nervous System Progression in Patients Receiving ALK-Targeted Central Nervous System-Penetrable Tyrosine Kinase Inhibitors: Treatment Patterns and Outcomes.

Surbhi Singhal, Caressa Hui, Joel W Neal, Seema Nagpal, Mohana Roy, Millie Das, Kavitha Ramchandran, Erqi Pollom, Giovanni Selvaggi, Heather A Wakelee, Nathaniel J Myall.

   Introduction: Central nervous system (CNS) metastases are common in ALK-rearranged NSCLC. The optimal treatment strategy for patients who develop CNS progression during treatment with CNS-penetrable ALK tyrosine kinase inhibitors (TKIs) is unknown. Here, we characterized practice patterns and outcomes for patients who developed CNS progression during treatment with CNS-penetrable TKI.
Methods: This retrospective study included patients who developed CNS progression (time 0, [T0]) on alectinib, lorlatinib, brigatinib, or ensartinib. Patients were characterized according to TKI management (i.e., TKI unaltered, TKI-altered [switched TKI or increased TKI dose], TKI discontinued) at T0. Intracranial progression-free survival was evaluated using Kaplan-Meier and compared using the log-rank test.
Results: Among 98 patients treated with a CNS-penetrable TKI, 36 (37%) experienced CNS progression. Overall, 33 (92%) developed parenchymal and seven (19%) developed leptomeningeal progression, respectively. At T0, 16 (44%) had TKI unaltered, 14 (39%) had TKI altered (eight switched TKI, six increased TKI dose), and six (17%) discontinued TKI. Patients with TKI-altered tended to have more frequent leptomeningeal disease or concurrent systemic progression at T0. Intracranial radiation was given at T0 in 14 (88%) of TKI-unaltered and three (21%) of TKI-altered patients. The median intracranial progression-free survival from T0 was not significantly different between the TKI-altered versus unaltered groups (p = 0.21).
Conclusions: For patients with ALK-rearranged NSCLC with leptomeningeal progression or concurrent systemic progression, TKI change or dose increase was a feasible salvage strategy for CNS progression during treatment with CNS-penetrable TKI.

Keywords:  ALK-rearranged NSCLC; Central nervous system progression; Intracranial metastases; Leptomeningeal disease; Targeted therapy

DOI:  https://doi.org/10.1016/j.jtocrr.2025.100914