Unveiling the pathogenesis of perineural invasion from the perspective of neuroactive molecules

Rosa, Michelle Melgarejo da; Sampaio, Maria Clara Pinheiro Duarte; Santos, Renata Virgínia Calvancanti; Sharjeel, Muhammad; Araújo, C.F.C.; Pitta, Maíra Galdino da Rocha; Pereira, Michelly Cristiny; Rego, Moacyr Jesus Barreto de Mello

doi:10.1016/j.bcp.2021.114547

Cited by 10 publications

(4 citation statements)

References 165 publications

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“…Seven were finally included in the final prediction nomogram. Based on the consensus, FLI and DSI indicate more locally invasive cancer ( 30 ). During this study, FLI and DSI were important predictors of PNI.…”

Section: Discussionmentioning

confidence: 99%

Preoperative Evaluation of Perineural Invasion in Cervical Cancer: Development and Independent Validation of a Novel Predictive Nomogram

et al. 2021

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BackgroundPerineural invasion (PNI) is associated with a poor prognosis for cervical cancer and influences surgical strategies. However, a preoperative evaluation that can determine PNI in cervical cancer patients is lacking.MethodsAfter 1:1 propensity score matching, 162 cervical cancer patients with PNI and 162 cervical cancer patients without PNI were included in the training set. Forty-nine eligible patients were enrolled in the validation set. The PNI-positive and PNI-negative groups were compared. Multivariate logistic regression was performed to build the PNI prediction nomogram.ResultsAge [odds ratio (OR), 1.028; 95% confidence interval (CI), 0.999–1.058], adenocarcinoma (OR, 1.169; 95% CI, 0.675–2.028), tumor size (OR, 1.216; 95% CI, 0.927–1.607), neoadjuvant chemotherapy (OR, 0.544; 95% CI, 0.269–1.083), lymph node enlargement (OR, 1.953; 95% CI, 1.086–3.550), deep stromal invasion (OR, 1.639; 95% CI, 0.977–2.742), and full-layer invasion (OR, 5.119; 95% CI, 2.788–9.799) were integrated in the PNI prediction nomogram based on multivariate logistic regression. The PNI prediction nomogram exhibited satisfactory performance, with areas under the curve of 0.763 (95% CI, 0.712–0.815) for the training set and 0.860 (95% CI, 0.758–0.961) for the validation set. Moreover, after reviewing the pathological slides of patients in the validation set, four patients initially diagnosed as PNI-negative were recognized as PNI-positive. All these four patients with false-negative PNI were correctly predicted to be PNI-positive (predicted p > 0.5) by the nomogram, which improved the PNI detection rate.ConclusionThe nomogram has potential to assist clinicians when evaluating the PNI status, reduce misdiagnosis, and optimize surgical strategies for patients with cervical cancer.

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Section: Discussionmentioning

confidence: 99%

Preoperative Evaluation of Perineural Invasion in Cervical Cancer: Development and Independent Validation of a Novel Predictive Nomogram

et al. 2021

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“…The tumor microenvironment (TME) is composed of complicated elements including immune cells, nerves, stroma, and so on, where cancers depend on tumorinvasion and metastasis. [4][5][6] For metastatic routes, malignant cells often spread by invading venous vessels, lymphatics channels, and nerve structures. A variety of invasive front markers can reflect tumor invasiveness and further metastatic behaviors, of which the tumor growth pattern (TGP) and perineural invasion (PNI) are closely related to tumor-invasion and metastatic routes.…”

Section: Introductionmentioning

confidence: 99%

“…10,11 PNI is characterized by neoplastic invasion and spread within the nerve structure, 12 closely associated with the interaction between tumor cells, stroma, and nerves in TME. 6 For CRC, PNI generally refers to tumor-invasion and an alternative route of metastasis via nerves, and thus serves as an independent prognostic factor of survival. 13,14 Moreover, the association between TGP and PNI has been elucidated in previous studies.…”

Section: Introductionmentioning

confidence: 99%

Development and validation of a scoring system incorporating tumor growth pattern and perineural invasion for risk stratification in colorectal cancer

Liu

Wang

Yao

et al. 2023

Journal of Investigative Medicine

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Tumor growth pattern (TGP) and perineural invasion (PNI) at the invasive margin have been recognized as indicators of tumor invasiveness and prognostic events in colorectal cancer (CRC). This study aims to develop a scoring system incorporating TGP and PNI, and further investigate its prognostic significance for CRC risk stratification. A scoring system, termed tumor-invasion score, was established by summing TGP and PNI scores. The discovery cohort (N = 444) and the validation cohort (N = 339) were used to explore the prognostic significance of the tumor-invasion score. The endpoints of the event were disease-free survival (DFS) and overall survival (OS) which were analyzed by the Cox proportional hazard model. In the discovery cohort, Cox regression analysis showed that DFS and OS were inferior for score 4 group compared with score 1 group (DFS, hazard ratio (HR) 4.44, 95% confidence interval (CI) 2.49–7.92, p < 0.001; OS, 4.41, 2.37–8.19,p < 0.001). The validation cohort showed similar results (DFS, 4.73, 2.39–9.37, p < 0.001; OS, 5.52, 2.55–12.0, p < 0.001). The model combining tumor-invasion score and clinicopathologic information showed good discrimination performance than single predictors. TGP and PNI were associated with tumor invasiveness and survival in CRC. The tumor-invasion score generated by TGP and PNI scores served as an independent prognostic parameter of DFS and OS for CRC patients.

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“…Perineural invasion is a complex process mediated by multiple pathways 5 , 6 and has been shown to be associated with maladjusted genes 7 , 8 that regulate the release of tumor chemokines, 9 , 10 neurotropic factors, 11 and adhesion molecules 12 in nerve‐tumor microenvironment. Our preliminary research found the neurotrophic factors BDNF 13 and NGF participated in the PNI process of SACC.…”

Section: Introductionmentioning

confidence: 99%

The GAL/GALR2 axis promotes the perineural invasion of salivary adenoid cystic carcinoma via epithelial‐to‐mesenchymal transition

et al. 2022

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Background: Perineural invasion (PNI) is a typical pathological characteristic of salivary adenoid cystic carcinoma (SACC) and other neurotrophic cancers. The mechanism of the neural microenvironment controlling tumor progression during the PNI process is unclear. In the present study, we investigated the role and molecular mechanisms of nerve-derived neuropeptide galanin (GAL) and its receptor (GALR2) in the regulation of PNI in SACC. Methods: Immunohistochemistry staining and clinical association studies were performed to analyze the expression of GAL and GALR2 in SACC tissues and their clinical value. Dorsal root ganglion or SH-SY5Y cells were co-cultured with SACC cells in vitro to simulate the interactions between the neural microenvironment and tumor cells, and a series of assays including transcriptome sequencing, Western blot, and Transwell were performed to investigate the role and molecular mechanism of GAL and GALR2 in the regulation of SACC cells. Moreover, both the in vitro and in vivo PNI models were established to assess the potential PNI-specific therapeutic effects by blocking the GAL/GALR2 axis. Results: GAL and GALR2 were highly expressed in SACC tissues, and were associated with PNI and poor prognosis in SACC patients (p < 0.05). Nerve-derived GAL activated GALR2 expression in SACC cells and induced epithelial-tomesenchymal transition (EMT) in SACC cells. Adding human recombinant GAL to the co-culture system promoted the proliferation, migration, and invasion of SACC cells significantly, but inhibited the apoptosis of SACC cells. Adding M871, a specific antagonist of GALR2, significantly blocked the above effects (p < 0.05) and inhibited the PNI of SACC cells in vitro and in vivo (p < 0.05). Conclusions: This study demonstrated that nerve-derived GAL activated GALR2 expression, and promoted EMT in SACC cells, thereby enhancing the | 4497 WANG et al. How to cite this article: Wang J, Yang Z, Liu Y, et al. The GAL/GALR2 axis promotes the perineural invasion of salivary adenoid cystic carcinoma via epithelial-to-mesenchymal transition.

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Unveiling the pathogenesis of perineural invasion from the perspective of neuroactive molecules

Cited by 10 publications

References 165 publications

Preoperative Evaluation of Perineural Invasion in Cervical Cancer: Development and Independent Validation of a Novel Predictive Nomogram

Preoperative Evaluation of Perineural Invasion in Cervical Cancer: Development and Independent Validation of a Novel Predictive Nomogram

Development and validation of a scoring system incorporating tumor growth pattern and perineural invasion for risk stratification in colorectal cancer

The GAL/GALR2 axis promotes the perineural invasion of salivary adenoid cystic carcinoma via epithelial‐to‐mesenchymal transition

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