Review
Oncology
Yuequn Niu, Sarah Foerster, Michael Muders
Summary: Perineural invasion (PNI) is a common indicator of tumor metastasis in various malignancies, including prostate cancer. PNI involves the interaction between tumor cells and nerve components in the tumor microenvironment, creating a perineural niche that supports tumor cell survival and invasion, benefiting nerve cells. The molecular mechanisms of PNI are still limitedly understood. Clinically, PNI is associated with adverse clinicopathological parameters and poor outcomes for prostate cancer patients. However, there is controversy over whether PNI can act as an independent prognostic predictor due to inconsistent research aims, sample types, statistical methods, and the definition and inclusion criteria. This review summarizes and compares the prognostic significance of PNI in prostate cancer based on existing literature and suggests that a more standardized description of PNI would enhance the understanding of its clinical relevance.
Article
Health Care Sciences & Services
Yi-Fu Chen, Shan-Yu Wang, Puo-Hsien Le, Tsung-Hsing Chen, Chia-Jung Kuo, Chun-Jung Lin, Wen-Chi Chou, Ta-Sen Yeh, Jun-Te Hsu
Summary: The prognostic significance of perineural invasion in patients with stage II/III gastric cancer undergoing radical surgery is still under debate. This study aimed to determine the prognostic value of perineural invasion in these patients and found that perineural invasion is independently associated with aggressive tumor behaviors and higher recurrence rates, making it an unfavorable prognostic factor.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Review
Oncology
Jialun Wang, Yu Chen, Xihan Li, Xiaoping Zou
Summary: Perineural invasion is a complex process that occurs in many malignant tumors, including gastric carcinoma, biliary tract tumor, and pancreatic cancer. It is associated with poor survival and decreased quality of life in pancreatic cancer patients. Studies have revealed subtle molecule regulatory mechanisms during perineural invasion and its potential causal link with pancreatic cancer-associated pain.
Review
Pharmacology & Pharmacy
Rong-jia Shi, Bo-wen Ke, Ya-ling Tang, Xin-hua Liang
Summary: Perineural invasion (PNI) is the process of tumor invasion and interaction with nerves, causing dynamic changes and disturbing symptoms. PNI-related cancer pain in neuro-rich tumors is closely related to nerve invasion in the tumor microenvironment, and can indicate the occurrence of PNI, guide treatment strategies, and predict tumor resectability and the need for palliative care.
BIOCHEMICAL PHARMACOLOGY
(2023)
Review
Oncology
Federico Selvaggi, Eugenia Melchiorre, Ilaria Casari, Sebastiano Cinalli, Massimiliano Cinalli, Gitana Maria Aceto, Roberto Cotellese, Ingrid Garajova, Marco Falasca
Summary: Pancreatic ductal adenocarcinoma is highly threatening and characterized by perineural invasion (PNI), which is associated with recurrence, poor prognosis, and pain. Researchers are currently seeking more effective therapies to inhibit the nerve invasion promoted by pancreatic ductal adenocarcinoma.
Review
Oncology
Jingbo Li, Rui Kang, Daolin Tang
Summary: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignant disease characterized by a unique tumor microenvironment surrounded by an interlaced network of cancer and noncancerous cells. Recent studies have shown that the dynamic interaction between cancer cells and neuronal cells leads to perineural invasion (PNI), which is closely related to tumor development, growth, invasion, metastasis, and poor disease prognosis. The formation and function of PNI are regulated by various mechanisms involving molecular, metabolic, and cellular factors, providing opportunities for further exploration to benefit PDAC patients.
CANCER COMMUNICATIONS
(2021)
Review
Oncology
Hao Wang, Ruixue Huo, Kexin He, Li Cheng, Shan Zhang, Minhao Yu, Wei Zhao, Hui Li, Junli Xue
Summary: In recent years, the importance of the nervous system in the tumor microenvironment has been recognized. The bidirectional communication between nerves and cancer cells is crucial for tumor initiation and progression. Perineural invasion (PNI) is a common feature in various malignancies and is associated with tumor invasion, metastasis, cancer-related pain, and unfavorable clinical outcomes. It is essential to investigate the role of nerves in colorectal cancer (CRC) and understand the mechanisms of PNI in order to impede tumor progression and improve patient survival.
Article
Multidisciplinary Sciences
Andrea R. Marcadis, Elizabeth Kao, Qi Wang, Chun-Hao Chen, Laxmi Gusain, Ann Powers, Richard L. Bakst, Sylvie Deborde, Richard J. Wong
Summary: The invasion of nerves by cancer cells, or perineural invasion (PNI), is influenced by the nerve microenvironment and is associated with negative clinical outcomes. However, the specific characteristics of cancer cells that enable PNI have not been well defined. Through serial passaging of pancreatic cancer cells in a murine sciatic nerve model of PNI, we generated cell lines enriched for a rapid neuroinvasive phenotype. These leading neuroinvasive cells exhibited upregulation of proteins involving the plasma membrane, cell leading edge, and cell movement. They also underwent phenotypic changes from a mesenchymal to an amoeboid phenotype, and acquired increased migration ability and affinity for dorsal root ganglia. Inhibition of ROCK reversed these changes and reduced PNI in a murine sciatic nerve model. This study highlights the plasticity of cancer migration mode in facilitating rapid nerve invasion.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Priyanka Narayan, Jessica Flynn, Zhigang Zhang, Erin F. Gillespie, Boris Mueller, Amy J. Xu, John Cuaron, Beryl McCormick, Atif J. Khan, Oren Cahlon, Simon N. Powell, Hannah Wen, Lior Z. Braunstein
Summary: This study explored the association between perineural invasion (PNI) and locoregional recurrence (LRR) in breast cancer patients, finding that PNI significantly increases the risk of LRR. Multivariable Fine-Gray regression modeling confirmed the potentiated association between PNI and LRR. Propensity score matching analysis further supported the significant link between PNI and LRR.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Wunai Zhang, Rui He, Wenbin Yang, Yan Zhang, Qinggong Yuan, Jixin Wang, Yang Liu, Shuo Chen, Simei Zhang, Weifan Zhang, Zeen Zhu, Jing Zhang, Zheng Wang, Junhui Li
Summary: Autophagy and perineural invasion (PNI) in pancreatic cancer have negative effects on prognosis. Schwann cells (SCs) in PNI are activated through NGF-mediated autophagy, promoting PNI by enhancing migration and axon guidance towards cancer cells and increasing chemoattraction. Targeting NGF and autophagy for PNI treatment can block nerve infiltration.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Tao Qin, Jie Li, Ying Xiao, Xueni Wang, Mengyuan Gong, Qiqi Wang, Zeen Zhu, Simei Zhang, Wunai Zhang, Fang Cao, Liang Han, Zheng Wang, Qingyong Ma, Huanchen Sha
Summary: The study showed that HNK can inhibit the invasion and migration of pancreatic cancer cells, as well as the PNI of pancreatic cancer, partially through inhibition of SMAD2/3 phosphorylation. In vivo, HNK was found to suppress EMT in pancreatic cancer, inhibit cancer cell migration along the nerve, reduce damage to the sciatic nerve caused by tumor cells, and protect the function of the sciatic nerve.
FRONTIERS IN ONCOLOGY
(2021)
Article
Cell Biology
Zhen Zheng, Xiao Li, Guoqiang Chen, Jing Chen, Xiaolu Zhu, Yincheng Teng
Summary: Perineural invasion (PNI) is found to be a significant independent prognostic factor in ovarian cancer (OC) patients, with shorter overall survival (OS) time. PNI positivity is negatively correlated with immune killer cell infiltration in OC tumor tissues. TAS2R proteins are upregulated in PNI-positive OC tissues and predict poor prognoses.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Oncology
Dawid Sigorski, Jacek Gulczynski, Aleksandra Sejda, Wojciech Rogowski, Ewa Izycka-Swieszewska
Summary: The study revealed differences in neural parameters between prostate cancer and benign prostate, with a heterogeneous neural network in PCa. Higher neural density was observed in the surrounding and invasive front of the tumor. NPY expression, neuroendocrine differentiation, and ERG status were found to be related to ND and PNI. The findings provide evidence for autocrine and paracrine interactions in the neural microenvironment of prostate cancer.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Dominika Czaplinska, Renata Ialchina, Henriette Berg Andersen, Jiayi Yao, Arnaud Stigliani, Johs Dannesboe, Mette Flinck, Xiaoming Chen, Jakub Mitrega, Sebastian Peter Gnosa, Oksana Dmytriyeva, Frauke Alves, Joanna Napp, Albin Sandelin, Stine Falsig Pedersen
Summary: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with limited treatment options and increasing prevalence worldwide. This study reveals a complex interplay between tumor acidosis, extracellular matrix composition, and genotype in PDAC development. The findings may provide guidance for future acidosis-targeted therapies.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Review
Biochemistry & Molecular Biology
Mei Zhang, Hong-chun Xian, Li Dai, Ya-ling Tang, Xin-hua Liang
Summary: Perineural invasion (PNI) is a common clinical feature in malignant tumors that can lead to postoperative recurrence and metastasis. Recent studies have shown that miRNA plays a crucial role in regulating PNI, offering potential new biomarkers and therapeutic targets for cancer treatment.
CELL AND BIOSCIENCE
(2021)
Article
Biochemical Research Methods
Rong Tang, Zijian Wu, Zeyin Rong, Jin Xu, Wei Wang, Bo Zhang, Xianjun Yu, Si Shi
Summary: This study developed an accurate prognostic model based on the expression patterns of ferroptosis-associated lncRNAs, which can contribute greatly to the evaluation of patient prognosis, molecular characteristics, and treatment modalities in PDAC. The study identified novel ferroptosis-related lncRNAs and validated their role in ferroptosis resistance. There were significant differences between patients with different risk scores and potential drugs for the treatment of low-risk patients were identified.
BRIEFINGS IN BIOINFORMATICS
(2022)
Article
Biochemistry & Molecular Biology
Zhen Tan, Si Shi, Jin Xu, Xiaomeng Liu, Yubin Lei, Bo Zhang, Jie Hua, Qingcai Meng, Wei Wang, Xianjun Yu, Chen Liang
Summary: This study reveals that downregulation of FTO leads to increased m(6)A modifications in the 3'UTR of PDGFC, and then modulates its transcriptional level in an m(6)A-YTHDF2-dependent manner. PDGFC upregulation promotes cell growth, highlighting a potential therapeutic target for PDAC treatment and prognostic prediction.
Review
Oncology
Xuhui Tong, Rong Tang, Mingming Xiao, Jin Xu, Wei Wang, Bo Zhang, Jiang Liu, Xianjun Yu, Si Shi
Summary: This article discusses the molecular processes and effects of necroptosis, pyroptosis, ferroptosis, and cuproptosis on tumor cell proliferation and cancer metastasis, as well as the complex effects of these novel types of tumor cell death on the tumor microenvironment and regulated death of other cells in the microenvironment.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2022)
Article
Oncology
Xiaomeng Liu, Jiang Liu, Jin Xu, Bo Zhang, Miaoyan Wei, Jialin Li, Hang Xu, Xianjun Yu, Wei Wang, Si Shi
Summary: This study discovered the important role of adipocytes in pancreatic ductal adenocarcinoma (PDAC), as high levels of adipocyte infiltration were associated with enhanced immune response and lower tumor mutational burden. Through mouse experiments and analysis of PDAC samples, the study provides a new perspective on the activation of the immune microenvironment in PDAC.
TRANSLATIONAL ONCOLOGY
(2023)
Review
Oncology
Zengli Fang, Qingcai Meng, Jin Xu, Wei Wang, Bo Zhang, Jiang Liu, Chen Liang, Jie Hua, Yingjun Zhao, Xianjun Yu, Si Shi
Summary: Cancer-associated fibroblasts (CAFs) play important roles in tumor initiation and progression, and their characteristics and malignant phenotype are regulated by signaling pathways and transcription factors in the tumor microenvironment. Targeting signaling pathways in CAFs shows promise in cancer therapy, but there are also challenges and failures. Understanding the signaling cascades in CAFs helps us better understand their roles in cancer progression and may lead to the development of more effective and safer therapies.
CANCER COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Chen Liang, Zeyin Rong, Abudureyimu Tuerhong, Qingcai Meng, Jie Hua, Jiang Liu, Bo Zhang, Wei Wang, Xianjun Yu, Si Shi, Jin Xu
Summary: Pancreatic cancer is a highly deadly malignancy with desmoplastic stroma and metabolic reprogramming as its key features. The underlying mechanism of the stroma's role in maintaining redox balance in pancreatic ductal adenocarcinoma (PDAC) remains unclear. This study demonstrates that the physical properties of the stroma can regulate the expression of PIN1 in PDAC cells. PIN1, through its synergistic activation of NRF2 transcription, promotes the expression of intracellular antioxidant response element (ARE)-driven genes, leading to increased antioxidant stress ability and decreased intracellular level of reactive oxygen species (ROS) in PDAC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Zhilong Ma, Wangcheng Xie, Tingyi Luo, Zhengyu Hu, Jie Hua, Jia Zhou, Tingsong Yang, Wei Wang, Zhenshun Song, Xianjun Yu, Jin Xu, Si Shi
Summary: Severe acute pancreatitis is a common critical digestive system disease with high mortality and a lack of effective prevention and treatment measures. This study revealed the therapeutic role of exosomes from TNF-α-preconditioned human umbilical cord mesenchymal stromal cells in attenuating SAP, and showed that it is partly dependent on exosomal metabolites.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Gastroenterology & Hepatology
Xiaomeng Liu, Rong Tang, Jin Xu, Zhen Tan, Chen Liang, Qingcai Meng, Yubin Lei, Jie Hua, Yiyin Zhang, Jiang Liu, Bo Zhang, Wei Wang, Xianjun Yu, Si Shi
Summary: This study reveals that CRIP1 plays a critical role in immune evasion and tumour immune microenvironment (TIME) formation in PDAC. CRIP1 binds to NF-κB/p65 and facilitates its nuclear translocation, leading to the transcriptional activation of CXCL1/5. PDAC-derived CXCL1/5 promotes the chemotactic migration of MDSCs, resulting in immunosuppression. Inhibition of CXCR1/2 and combination therapy with anti-PD-L1 enhances CD8+T cell infiltration and exhibits potent antitumor activity in PDAC.
Article
Oncology
Mingwei Dong, Rong Tang, Wei Wang, Jin Xu, Jiang Liu, Chen Liang, Jie Hua, Qingcai Meng, Xianjun Yu, Bo Zhang, Si Shi
Summary: By analyzing single-nucleus RNA sequencing, it was found that pancreatic ductal adenocarcinoma (PDAC) is highly heterogeneous and lacks comprehensive understanding of its classification and tumor microenvironment. Hypoxia is an important feature of PDAC and plays a potential regulatory role in tumor progression and aggressive phenotype. PDAC with high hypoxia tends to present basal/squamous-like phenotype and has increased outgoing signaling, promoting tumor cell stemness, metastasis, angiogenesis, and fibroblast differentiation. Hypoxia is also associated with an extracellular matrix enriched microenvironment and increased possibility of TP53 mutation in PDAC.
TRANSLATIONAL ONCOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Jing Yang, Jin Xu, Wei Wang, Bo Zhang, Xianjun Yu, Si Shi
Summary: Researchers have focused on the epigenetic control of DNA-templated processes for many years. Epigenetic modifications like histone modification, DNA methylation, chromatin remodeling, RNA modification, and noncoding RNAs play a crucial role in the development of cancers. Dysregulation of the epigenome leads to abnormal transcriptional programs, and targeting the dysregulated epigenetic modifications might be an effective strategy for cancer treatment. Additionally, epigenetics influences tumor immunogenicity and immune cells involved in antitumor responses, suggesting the potential of combining epigenetic therapy and cancer immunotherapy for better cancer treatment.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)
Article
Biochemistry & Molecular Biology
Qingcai Meng, Zengli Fang, Xiaoqi Mao, Rong Tang, Chen Liang, Jie Hua, Wei Wang, Si Shi, Xianjun Yu, Jin Xu
Summary: This study aims to explore the impact of metabolic changes in cancer-associated fibroblasts (CAFs) on the heterogeneity of PET-CT. The results showed that CAFs with high glycolytic activity contribute to malignant behavior in pancreatic cancer, and high SUVmax may serve as a marker for therapy targeting the tumor stroma.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Si-Yuan Lu, Jie Hua, Jiang Liu, Miao-Yan Wei, Chen Liang, Qing-Cai Meng, Bo Zhang, Xian-Jun Yu, Wei Wang, Jin Xu, Si Shi
Summary: Evidence suggests a correlation between necroptosis and pancreatic cancer, and the relationship between necroptosis, immune infiltration, and the microenvironment in pancreatic cancer has gained attention. A two-dimensional phenotype based on necroptosis and immunity was developed, showing that a high necroptosis phenotype and high immunity phenotype were associated with better prognosis. This study has potential clinical applications in predicting and individualizing treatment decisions for pancreatic cancer.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Endocrinology & Metabolism
Xinzhe Zhu, Huaxiang Xu, Zhiwen Xiao, He Liu, Quanxing Ni, Xianjun Yu, Guopei Luo
Summary: This study investigated the impact of hyperglycemia on the prognosis of patients with advanced pancreatic cancer. Among patients without a history of diabetes, 25.3% were diagnosed with hyperglycemia, which was associated with worse prognosis (median survival of 7.5 months vs. 8.8 months). Hyperglycemia predicted worse overall survival in patients with advanced pancreatic cancer.
Review
Biochemistry & Molecular Biology
Mingming Xiao, Jin Xu, Wei Wang, Bo Zhang, Jiang Liu, Jialin Li, Hang Xu, Yingjun Zhao, Xianjun Yu, Si Shi
Summary: Cholesterol plays a critical role in maintaining cellular activities by contributing to membrane integrity and fluidity. Recent research has shown that cholesterol metabolism is closely involved in cancer progression through its regulatory effects on various cellular processes. Understanding the role of cholesterol metabolism in cancer could lead to new strategies for cancer treatment.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Xuhui Tong, Rong Tang, Jin Xu, Wei Wang, Yingjun Zhao, Xianjun Yu, Si Shi
Summary: Liquid-liquid phase separation (LLPS) is a novel principle that explains the precise regulation of spatial and temporal organization in living cells. It plays a crucial role in various cellular processes and its dysregulation has been linked to cancer development. This review comprehensively summarizes the mechanisms of biomolecular condensate formation and function, and discusses recent advances in understanding the role of aberrant LLPS in cancer pathology. Furthermore, the therapeutic potential of targeting LLPS in cancer research and development of drug candidates is also discussed.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2022)
