bims-netuvo Biomed News
on Nerves in tumours of visceral organs
Issue of 2023–10–15
nine papers selected by
Maksym V. Kopanitsa, The Francis Crick Institute



  1. Int J Mol Sci. 2023 Oct 08. pii: 14989. [Epub ahead of print]24(19):
      Pancreatic ductal adenocarcinoma (PDAC) represents one of the most aggressive solid tumors with a dismal prognosis and an increasing incidence. At the time of diagnosis, more than 85% of patients are in an unresectable stage. For these patients, chemotherapy can prolong survival by only a few months. Unfortunately, in recent decades, no groundbreaking therapies have emerged for PDAC, thus raising the question of how to identify novel therapeutic druggable targets to improve prognosis. Recently, the tumor microenvironment and especially its neural component has gained increasing interest in the pancreatic cancer field. A histological hallmark of PDAC is perineural invasion (PNI), whereby cancer cells invade surrounding nerves, providing an alternative route for metastatic spread. The extent of PNI has been positively correlated with early tumor recurrence and reduced overall survival. Multiple studies have shown that mechanisms involved in PNI are also involved in tumor spread and pain generation. Targeting these pathways has shown promising results in alleviating pain and reducing PNI in preclinical models. In this review, we will describe the mechanisms and future treatment strategies to target this mutually trophic interaction between cancer cells to open novel avenues for the treatment of patients diagnosed with PDAC.
    Keywords:  crosstalk; microenvironment; neuron; pancreatic ductal adenocarcinoma
    DOI:  https://doi.org/10.3390/ijms241914989
  2. J Cell Mol Med. 2023 Oct 13.
      Perineural invasion (PNI) has emerged as a key pathological feature and be considered as a poor prognostic factor in cervical cancer. However, the underlying molecular mechanisms are largely unknown. Here, PNI status of 269 cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) samples were quantified by using whole-slide diagnostic images obtained from The Cancer Genome Atlas. Integrated analyses revealed that PNI was an indicative marker of poorer disease-free survival for CESC patients. Among the differentially expressed genes, ADCYAP1 were identified. Clinical specimens supported that high expression of PACAP (encoded by ADCYAP1) contributed to PNI in CESC. Mechanistically, PACAP, secreted from cervical cancer cells, reversed myelin differentiation of Schwann cells (SCs). Then, dedifferentiated SCs promoted PNI by producing chemokine FGF17 and by degrading extracellular matrix through secretion of Cathepsin S and MMP-12. In conclusion, this study identified PACAP was associated with PNI in cervical cancer and suggested that tumour-derived PACAP reversed myelin differentiation of SCs to aid PNI.
    Keywords:  Schwann cells; cervical cancer; dedifferentiated; perineural invasion; pituitary adenylate cyclase-activating polypeptide
    DOI:  https://doi.org/10.1111/jcmm.17897
  3. Int J Gen Med. 2023 ;16 4549-4563
       Background: Colon cancer is a prevalent gastrointestinal malignancy that often exhibits distant metastasis, hindering the effectiveness of surgical interventions. In addition to well-known hematogenous and lymphatic metastasis, perineural invasion (PNI) has emerged as a significant mode of distant metastasis in colon tumors. PNI is closely associated with oncologic pain in advanced cancer patients, but the underlying mechanisms and associated biomarkers, which might be the novel therapeutic targets, remain poorly understood.
    Methods: In this study, we employed large databases and bioinformatics methods to identify genes strongly linked to PNI in colon cancer and investigated their involvement in tumor nerve invasion, progression mechanisms, and chemotherapy resistance. Immunohistochemical techniques were utilized to validate the expression of target genes in 384 colon cancer tissues, and their expression was correlated with clinicopathological characteristics and patient survival data in our hospital. Furthermore, we conducted a comprehensive literature review to explore the potential functions of the target genes and their associated genes.
    Results: Our screening revealed a significant correlation between neural proliferation differentiation and control-1 (NPDC1) expression and patient prognosis, suggesting a potential association with neural infiltration in colon cancer. Additionally, NPDC1 may promote tumorigenesis, progression, and chemoresistance through various related pathways.
    Conclusion: Our study provides novel insights into the utility of NPDC1 as a predictive marker for PNI status, disease-free survival, and overall survival in patients with colon cancer, highlighting the prevalence of NPDC1 overexpression in patients with PNI in colon cancer.
    Keywords:  NPDC1; PNI; clinicopathological features; colon cancer; neural proliferation differentiation and control-1; perineural invasion
    DOI:  https://doi.org/10.2147/IJGM.S428590
  4. Clin Radiol. 2023 Sep 28. pii: S0009-9260(23)00428-2. [Epub ahead of print]
       AIM: To investigate the potential of intravoxel incoherent motion (IVIM) diffusion-weighted imaging to predict perineural invasion (PNI) preoperatively in resectable gastric cancer (GC).
    MATERIALS AND METHODS: This study prospectively recruited 85 surgically resected GC patients (58 men, 27 women) aged 60.87 ± 10.17 (39-81) years, who underwent IVIM sequence within 1 week before surgery. According to histopathological PNI diagnoses, patients were divided into PNI positive and negative groups. Conventional apparent diffusion coefficient (ADC) and the IVIM parameters, including true diffusion coefficient (D), pseudodiffusion coefficient (D∗), and pseudodiffusion fraction (f), were compared between the two groups. Morphological MRI features were also analysed. Multivariate logistic regression was used to screen independent predictors of PNI. Receiver-operating characteristic curve analyses were preformed to evaluate the efficacy. Spearman's correlation test was performed to analyse the relationship between MRI parameters and PNI.
    RESULTS: Tumour thickness and f in PNI-positive group were higher, whereas the ADC, D were lower than those in PNI-negative group (p<0.05). These four parameters correlated with PNI (p<0.05). The D, f, and tumour thickness were independent predictors of PNI. The area under the curve of ADC, D, f, thickness, and the combined parameter (D + f + thickness) were 0.648, 0.745, 0.698, 0.725, and 0.869, respectively. The combined parameter demonstrated higher efficacy than any other parameters (p<0.05).
    CONCLUSION: The ADC, D, and f can effectively distinguish PNI status in GC. The D, f, and thickness were independent predictors of PNI.
    DOI:  https://doi.org/10.1016/j.crad.2023.09.014
  5. Ann Med Surg (Lond). 2023 Oct;85(10): 5239-5241
       Introduction: Schwannomas are benign tumors of the peripheral nerve sheath, and the median nerve is the most commonly involved nerve. These benign tumors of the peripheral nerve sheath are very rare; they are clinically and radiologically similar to most other benign swellings of the hand; thus, they are often misdiagnosed.
    Case Presentation: A 41-year-old lady presented with an 8-year-long history of swelling over the distal forearm. The tumor measured 3.5×3.5×3.5 mm and was located over the flexor aspect of the distal part of her right forearm. Schwannoma was suspected from the clinical presentation and imaging, but the final diagnosis was established only after the surgery and histopathological analysis. At the follow-up after 1 year, the patient is doing well and her symptoms have not recurred.
    Conclusion: Imaging characteristics of schwannoma can be misinterpreted as some other condition, making the preoperative diagnosis very difficult and important. Thus, clinicians should be aware of such swellings, especially those that have been unnoticed or misdiagnosed, and provide optimal diagnoses to confer good outcomes.
    Keywords:  case report; excision; median nerve; nerve sheath; schwannoma; tumor
    DOI:  https://doi.org/10.1097/MS9.0000000000001236
  6. Diagn Pathol. 2023 Oct 13. 18(1): 112
      Schwannomas are benign, generally indolent tumors of neural crest origin and comprise the most common histologic tumor of peripheral nerves. Schwannomas are a rare histology for retroperitoneal tumors and very rare histologic findings for tumors of the adrenal gland with fewer than 50 cases in the reported literature. Here we present a case report of a non-hormonally functional but metabolically active adrenal tumor with indeterminate imaging characteristics with final pathology showing a 6.1 cm adrenal schwannoma as well as historical institutional pathology review revealing two additional cases.
    Keywords:  Adrenal Tumor; Adrenal gland; Adrenal nodule; Adrenal schwannoma; Adrenalectomy
    DOI:  https://doi.org/10.1186/s13000-023-01399-5
  7. Curr Opin Oncol. 2023 Nov 01. 35(6): 558-563
       PURPOSE OF REVIEW: In recent years emerging evidence suggests that some tumor types, extremely rare in general population and understudied, can be observed in NF1 and neoplasms related with this condition harbor peculiar genetic and epigenetic features. The aim of this review is to summarize recent advances that, delving into the tumor complexity, have identified new diagnostic tools and potential tumor subtype that may have been associated with clinical implications.
    RECENT FINDINGS: The available data confirmed the presence of peculiar molecular signatures in those tumors, different from those observed in sporadic neoplasms and suggest that a specific reference to NF1 associated neoplasms would deserve to be mentioned in tumor WHO classification. Comprehensive multiomic analysis shows that the histologic assessment does not always match the methylation group assignment and facilitates tumor subclassification into categories predictive of clinical behavior. The non-invasive assessment of tumor genetic profiles by the analysis of plasma ctDNA is representative of tumor features, may help differential diagnosis and may identify malignant transformation, sparing the patient from repeated biopsies.
    SUMMARY: A better knowledge of NF1 associated tumors at the molecular level may suggest changes in the clinical management of the disease and open new frontiers of personalized treatment.
    DOI:  https://doi.org/10.1097/CCO.0000000000000998
  8. Cancer Discov. 2023 Oct 13. OF1
      Small cell lung cancer (SCLC) cell-astrocyte cross-talk drives a brain development program and SCLC growth.
    DOI:  https://doi.org/10.1158/2159-8290.CD-RW2023-162
  9. Asian J Surg. 2023 Oct 11. pii: S1015-9584(23)01527-0. [Epub ahead of print]
      
    Keywords:  Lumbar disc protrusion; Preoperative diagnosis; Schwannoma; Surgical treatment
    DOI:  https://doi.org/10.1016/j.asjsur.2023.09.112