bims-netuvo Biomed News
on Nerves in tumours of visceral organs
Issue of 2023–08–06
eight papers selected by
Maksym V. Kopanitsa, The Francis Crick Institute
  1. How can cancer research be illuminated by brain research (and vice versa)?
  2. Schwann cells regulate tumor cells and cancer-associated fibroblasts in the pancreatic ductal adenocarcinoma microenvironment.
  3. Promoter hypermethylation of neural-related genes is compatible with stemness in solid cancers.
  4. Comprehensive analysis of predictive factors for upstaging in intraprostatic cancer after radical prostatectomy: Different patterns of spread exist in lesions at different locations.
  5. Adrenal and periadrenal schwannoma: histological, molecular and clinical characterization of an institutional case series.
  6. Risk factors for distant metastasis in extrahepatic bile duct cancer after curative resection (KROG 1814).
  7. Pancreatic schwannoma: a rare tumor of the pancreas.
  8. The relationship between antidepressants and breast cancer: evidence from Mendelian randomization.
  1. Int J Cancer. 2023 Aug 03.
    How can cancer research be illuminated by brain research (and vice versa)?
    Alexios-Fotios A Mentis, Kostas A Papavassiliou, Christina Piperi, Athanasios G Papavassiliou.
      Cancer and brain research have historically followed concrete pathways and converged mostly to studying brain cancer. Nowadays, the fields of neuro-oncology and neuroendocrine regulation of tumorigenesis are both emerging fields of intense research and promising applications. An increasing body of evidence suggests that somatic mutations in cancer-related genes are prevalent in several noncancerous brain disorders. These findings highlighting that certain aspects of cancer development/progression and pathologies of the nervous system share molecular alterations, could assist in elucidating the unique hallmarks of cancer and in cancer drugs repurposing for brain disorders. In so doing, identifying the commonalities in these conditions could be crucial not only for better understanding the basis of these pathologies but also for considering the previously underappreciated and/or neglected possibility of using drugs known to be effective in one type of pathology for the other type.
    Keywords:  Alzheimer disease; brain; cancer; next-generation sequencing
    DOI:  https://doi.org/10.1002/ijc.34682
  2. Nat Commun. 2023 07 31. 14(1): 4600
    Schwann cells regulate tumor cells and cancer-associated fibroblasts in the pancreatic ductal adenocarcinoma microenvironment.
    Meilin Xue, Youwei Zhu, Yongsheng Jiang, Lijie Han, Minmin Shi, Rui Su, Liwen Wang, Cheng Xiong, Chaofu Wang, Ting Wang, Shijie Deng, Dong Wu, Yizhi Cao, Lei Dong, Fan Bai, Shulin Zhao, Xiaxing Deng, Chenghong Peng, Hongwei Li, Jianjun Chen, Baiyong Shen, Lingxi Jiang, Hao Chen.
      Neuropathy is a feature more frequently observed in pancreatic ductal adenocarcinoma (PDAC) than other tumors. Schwann cells, the most prevalent cell type in peripheral nerves, migrate toward tumor cells and associate with poor prognosis in PDAC. To unveil the effects of Schwann cells on the neuro-stroma niche, here we perform single-cell RNA-sequencing and microarray-based spatial transcriptome analysis of PDAC tissues. Results suggest that Schwann cells may drive tumor cells and cancer-associated fibroblasts (CAFs) to more malignant subtypes: basal-like and inflammatory CAFs (iCAFs), respectively. Moreover, in vitro and in vivo assays demonstrate that Schwann cells enhance the proliferation and migration of PDAC cells via Midkine signaling and promote the switch of CAFs to iCAFs via interleukin-1α. Culture of tumor cells and CAFs with Schwann cells conditioned medium accelerates PDAC progression. Thus, we reveal that Schwann cells induce malignant subtypes of tumor cells and CAFs in the PDAC milieu.
    DOI:  https://doi.org/10.1038/s41467-023-40314-w
  3. Epigenetics Chromatin. 2023 Aug 03. 16(1): 31
    Promoter hypermethylation of neural-related genes is compatible with stemness in solid cancers.
    Musa Idris, Louis Coussement, Maria M Alves, Tim De Meyer, Veerle Melotte.
       BACKGROUND: DNA hypermethylation is an epigenetic feature that modulates gene expression, and its deregulation is observed in cancer. Previously, we identified a neural-related DNA hypermethylation fingerprint in colon cancer, where most of the top hypermethylated and downregulated genes have known functions in the nervous system. To evaluate the presence of this signature and its relevance to carcinogenesis in general, we considered 16 solid cancer types available in The Cancer Genome Atlas (TCGA).
    RESULTS: All tested cancers showed significant enrichment for neural-related genes amongst hypermethylated genes. This signature was already present in two premalignant tissue types and could not be explained by potential confounders such as bivalency status or tumor purity. Further characterization of the neural-related DNA hypermethylation signature in colon cancer showed particular enrichment for genes that are overexpressed during neural differentiation. Lastly, an analysis of upstream regulators identified RE1-Silencing Transcription factor (REST) as a potential mediator of this DNA methylation signature.
    CONCLUSION: Our study confirms the presence of a neural-related DNA hypermethylation fingerprint in various cancers, of genes linked to neural differentiation, and points to REST as a possible regulator of this mechanism. We propose that this fingerprint indicates an involvement of DNA hypermethylation in the preservation of neural stemness in cancer cells.
    Keywords:  DNA hypermethylation; Neural differentiation; Pan cancer; REST
    DOI:  https://doi.org/10.1186/s13072-023-00505-7
  4. Cancer Med. 2023 Aug 03.
    Comprehensive analysis of predictive factors for upstaging in intraprostatic cancer after radical prostatectomy: Different patterns of spread exist in lesions at different locations.
    Shangrong Wu, Yuchen Jiang, Zhengxin Liang, Shuaiqi Chen, Guangyu Sun, Shenfei Ma, Kaifei Chen, Ranlu Liu.
       BACKGROUND: Accurate assessment of the clinical staging is crucial for determining the need for radical prostatectomy (RP) in prostate cancer (PCa). However, the current methods for PCa staging may yield incorrect results. This study aimed to comprehensively analyze independent predictors of postoperative upstaging of intraprostatic cancer.
    METHODS: We conducted a retrospective analysis of data from intraprostatic cancer patients who underwent radical surgery between March 2019 and December 2022. Intraprostatic cancer was defined as a lesion confined to the prostate, excluding cases where multiparameter magnetic resonance imaging (mpMRI) showed the lesion in contact with the prostatic capsule. We assessed independent predictors of extraprostatic extension (EPE) and analyzed their association with positive surgical margin (PSM) status. In addition, based on the distance of the lesion from the capsule on mpMRI, we divided the patients into non-transition zone and transition zone groups for further analysis.
    RESULTS: A total of 500 patients were included in our study. Logistic regression analysis revealed that biopsy Gleason grade group (GG) (odds ratio, OR: 1.370, 95% confidence interval, CI: 1.093-1.718) and perineural invasion (PNI) (OR: 2.746, 95% CI: 1.420-5.309) were predictive factors for postoperative EPE. Both biopsy GG and PNI were associated with lateral (GG: OR: 1.270, 95% CI: 1.074-1.501; PNI: OR: 2.733, 95% CI: 1.521-4.911) and basal (GG: OR: 1.491, 95% CI: 1.194-1.862; PNI: OR: 3.730, 95% CI: 1.929-7.214) PSM but not with apex PSM (GG: OR: 1.176, 95% CI: 0.989-1.399; PNI: OR: 1.204, 95% CI: 0.609-2.381) after RP. Finally, PNI was an independent predictor of EPE in the transition zone (OR: 11.235, 95% CI: 2.779-45.428) but not in the non-transition zone (OR: 1.942, 95% CI: 0.920-4.098).
    CONCLUSION: PNI and higher GG may indicate upstaging of tumors in patients with intraprostatic carcinoma. These two factors are associated with PSM in locations other than the apex of the prostate. Importantly, cancer in the transition zone of the prostate is more likely to spread externally through nerve invasion than cancer in the non-transition zone.
    Keywords:  extraprostatic extension; multiparameter magnetic resonance imaging; perineural invasion; prostate cancer; radical prostatectomy
    DOI:  https://doi.org/10.1002/cam4.6401
  5. Endocrine. 2023 Aug 03.
    Adrenal and periadrenal schwannoma: histological, molecular and clinical characterization of an institutional case series.
    Adam Stenman, Henrik Falhammar, Jan Zedenius, C Christofer Juhlin.
       PURPOSE: Adrenal schwannoma (AS) and periadrenal schwannoma (PAS) are exceedingly rare Schwann cell tumors that develop from the adrenal medulla and periadrenal peripheral nerves respectively. The underlying genetic events are elusive.
    METHODS: We searched our institutional database for AS/PAS cases and reviewed the histology and clinical outcome. Comprehensive molecular work-up was performed.
    RESULTS: We found reports of 4 AS/PAS cases diagnosed between 1992 and 2022 among the 1248 adrenal lesions submitted for histopathology during the same time period (0.32%). Two patients were male, two were female, and the age span was 59-80 years. Median size was 70 mm (range 50-100 mm), and from a radiology perspective, the lesions were initially suspected of malignant lesions originating from either adrenals or kidneys. Hormonal analyses were normal in all cases. Histologically, three cases were annotated as cellular AS or PAS, and one case was annotated as microcystic AS. Molecular characterization using focused next-generation sequencing did not identify SMARCB1 or NF2 mutations, alterations previously associated to schwannoma at other anatomical sites. The postoperative period was without complications for all patients, and follow-up did not show any signs of relapse or metastatic disease.
    CONCLUSION: AS/PAS are rare neoplasms that are most often benign, and the molecular etiology is most likely not related to mutations in established schwannoma-related genes. Since these tumors may be misinterpreted as malignant, knowledge of this entity is essential for radiologists, endocrinologists, surgeons and pathologists.
    Keywords:  Adrenal; Molecular; Outcome; Pathology; Radiology; Schwannoma
    DOI:  https://doi.org/10.1007/s12020-023-03463-y
  6. Cancer Res Treat. 2023 Jul 31.
    Risk factors for distant metastasis in extrahepatic bile duct cancer after curative resection (KROG 1814).
    Younghee Park, Tae Hyun Kim, Kyubo Kim, Jeong Il Yu, Wonguen Jung, Jinsil Seong, Woo Chul Kim, Jin Hwa Choi, Ah Ram Chang, Bae Kwon Jeong, Byoung Hyuck Kim, Tae Gyu Kim, Jin Hee Kim, Hae Jin Park, Hyun Soo Shin, Jung Ho Im, Eui Kyu Chie.
       Purpose: Risk factors predicting distant metastasis (DM) in extrahepatic bile duct cancer (EHBDC) patients treated with curative resection were investigated.
    Materials and Methods: Medical records of 1418 EHBDC patients undergoing curative resection between Jan 2000 and Dec 2015 from 14 institutions were reviewed. After resection, 924 patients (67.6%) were surveilled without adjuvant therapy, 297 (21.7%) were treated with concurrent chemoradiotherapy (CCRT) and 148 (10.8%) with CCRT followed by chemotherapy. To exclude the treatment effect from innate confounders, patients not treated with adjuvant therapy were evaluated.
    Results: After a median follow-up of 36.7 months (range, 2.7 - 213.2), the 5-year distant metastasis-free survival (DMFS) rates was 57.7%. On multivariate analysis, perihilar or diffuse tumor (HR 1.391, p=0.004), poorly differentiated histology (HR 2.014, p=0.000), presence of perineural invasion (HR 1.768, p=0.000), positive nodal metastasis (HR 2.670, p=0.000) and preoperative CA 19-9≥37 U/ml (HR 1.353 p=0.000) were significantly associated with inferior DMFS. The DMFS rates significantly differed according to the number of these risk factors. For validation, patients who underwent adjuvant therapy were evaluated. In patients with ≥3 factors, additional chemotherapy after CCRT resulted in a superior DMFS compared with CCRT alone (5-year rate, 47.6% vs 27.7%, p=0.001), but the benefit of additional chemotherapy was not observed in patients with 0-2 risk factors.
    Conclusion: Tumor location, histologic differentiation, perineural invasion, lymph node metastasis, and preoperative CA 19-9 level predicted DM risk in resected EHBDC. These risk factors might help identifying a subset of patients who could benefit from additional chemotherapy after resection.
    Keywords:  Distant metastasis; Extrahepatic bile duct cancer; Risk factors
    DOI:  https://doi.org/10.4143/crt.2023.616
  7. Rev Esp Enferm Dig. 2023 Aug 04.
    Pancreatic schwannoma: a rare tumor of the pancreas.
    Jiasuo Jiang, Ting Pan, Jun Xu.
      Schwannomas are rarely detected in the pancreas. Preoperative diagnosis of this entity is still challenging so far, causing unnecessary radical resection, endoscopic ultrasonography or percutaneous biopsies. Presented here is a case of schwannoma occurring in the pancreatic head, confirmed by histopathology after pancreaticoduodenectomy.
    DOI:  https://doi.org/10.17235/reed.2023.9840/2023
  8. Cancer Causes Control. 2023 Aug 04.
    The relationship between antidepressants and breast cancer: evidence from Mendelian randomization.
    Dong Niu, Chenchen Li, Xiaoyu Yan, Haoran Qu, Yuling Zheng.
       BACKGROUND: The use of antidepressants has increased over the years, but the relationship between antidepressant use and the risk of breast cancer is not uniform because of confounding factors. We aimed to assess the effect of antidepressants on breast cancer risk using a two-sample Mendelian randomization (MR) approach.stet METHODS: Secondary data analysis was performed on pooled data from genome-wide association studies based on single-nucleotide polymorphisms that were highly correlated with antidepressants, SSRI drugs, and serotonin and prolactin levels were selected as instrumental variables to evaluate the association between antidepressants and SSRI drugs and prolactin levels with breast cancer and ER+/ER- breast cancer. We then performed a test of the hypothesis that SSRI drugs elevate prolactin concentrations. We performed two-sample Mendelian randomization analyses using inverse variance weighting, MR-Egger regression, and weighted median methods, respectively.
    RESULTS: There was no significant risk association between antidepressant and SSRI use and the development of breast cancer, ER-positive or ER-negative breast cancer (P > 0.05), and serotonin concentration was not associated with breast cancer risk (P > 0.05). There was a positive causal relationship between prolactin levels and breast cancer (IVW, P = 0.02, OR = 1.058) and ER-positive breast cancer (Weighted median, P = 0.043, OR = 1.141; IVW, P = 0.009, OR = 1.125). Results in SSRI medication and prolactin levels showed no association between SSRI analogs and prolactin levels (P > 0.05).
    CONCLUSION: Large MR analysis showed that antidepressants as well as SSRI drugs were not associated with breast cancer risk and the SSRI-prolactin-breast cancer hypothesis did not hold in our analysis.
    Keywords:  Antidepressants; Breast cancer; Cancer risk; Mendelian randomization
    DOI:  https://doi.org/10.1007/s10552-023-01766-z
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