Exploring the clinical significance of TPX2 in pancreatic cancer: from biomarker to immunotherapy

被引:0
作者
Zhang, Zhengguang [1 ,2 ]
Liu, Zixian [2 ]
Yao, Ying [3 ]
Li, Min [3 ]
Shen, Cunsi [4 ]
Zhou, Fuqiong [1 ]
机构
[1] Nanjing Univ Chinese Med, Nanjing Hosp Chinese Med, Cent Lab, Nanjing, Jiangsu, Peoples R China
[2] Nanjing Univ Chinese Med, Sch Med, Nanjing, Jiangsu, Peoples R China
[3] Nanjing Univ Chinese Med, Dept Oncol, Nanjing Hosp Chinese Med, Nanjing, Jiangsu, Peoples R China
[4] Nanjing Univ Chinese Med, Inst Pediat, Affiliated Hosp, Jiangsu Key Lab Childrens Hlth & Chinese Med, Nanjing, Peoples R China
基金
中国国家自然科学基金;
关键词
Pancreatic cancer; Bioinformatics; Xenopus kinesin-like protein 2; Immune microenvironment;
D O I
10.1007/s00210-024-03628-0
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Pancreatic cancer (PC) is a highly aggressive malignancy characterized by a dismal prognosis. The present study is designed to elucidate the pivotal role of Xenopus kinesin-like protein 2 (TPX2) as a biomarker with substantial clinical prognostic significance in PC. By conducting a comprehensive analysis of RNA sequencing data and protein expression profiles obtained from multiple databases, we observed a pronounced upregulation of TPX2 expression in PC tissues compared to normal pancreatic tissues. Importantly, TPX2 emerged as an independent prognostic factor, demonstrating remarkable diagnostic accuracy. Notably, its expression levels were found to be significantly associated with the PC immune microenvironment and sensitivity to various therapeutic modalities. Functional assays revealed that the silencing of TPX2 markedly inhibited PC cell proliferation, metastasis, and the growth of subcutaneous tumors in PC mouse models. These effects were potentially mediated by the activation of CD8+ T cell immune responses and the inhibition of cell cycle progression and adhesion mechanisms. Taken together, our findings indicate that TPX2 may serve as a critical biomarker for the diagnosis and clinical management of patients with PC.
引用
收藏
页码:6843 / 6864
页数:22
相关论文
共 40 条
[1]   Emerging biomarkers for early diagnosis of pancreatic cancer [J].
不详 .
EBIOMEDICINE, 2022, 79
[2]   Targeting the metabolism and immune system in pancreatic ductal adenocarcinoma: Insights and future directions [J].
Bandi, Dhana Sekhar Reddy ;
Sarvesh, Sujith ;
Farran, Batoul ;
Nagaraju, Ganji Purnachandra ;
El-Rayes, Bassel F. .
CYTOKINE & GROWTH FACTOR REVIEWS, 2023, 71 :26-39
[3]   Challenges and Opportunities for Pancreatic Cancer Immunotherapy [J].
Bear, Adham S. ;
Vonderheide, Robert H. ;
O'Hara, Mark H. .
CANCER CELL, 2020, 38 (06) :788-802
[4]   Facts and Hopes in Immunotherapy of Pancreatic Cancer [J].
Bockorny, Bruno ;
Grossman, Joseph E. ;
Hidalgo, Manuel .
CLINICAL CANCER RESEARCH, 2022, 28 (21) :4606-4617
[5]   Immunotherapy for pancreatic cancer: chasing the light at the end of the tunnel [J].
Brouwer, Thomas P. ;
Vahrmeijer, Alexander L. ;
de Miranda, Noel F. C. C. .
CELLULAR ONCOLOGY, 2021, 44 (02) :261-278
[6]  
Cabasag CJ., 2021, GUT, V71, P2021
[7]   Drug resistance in pancreatic cancer: New player caught in act [J].
Capurso, Gabriele ;
Sette, Claudio .
EBIOMEDICINE, 2019, 40 :39-40
[8]   Computational analysis of cancer genome sequencing data [J].
Cortes-Ciriano, Isidro ;
Gulhan, Doga C. ;
Lee, Jake June-Koo ;
Melloni, Giorgio E. M. ;
Park, Peter J. .
NATURE REVIEWS GENETICS, 2022, 23 (05) :298-314
[9]   Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing [J].
Cortes-Ciriano, Isidro ;
Lee, Jake June-Koo ;
Xi, Ruibin ;
Jain, Dhawal ;
Jung, Youngsook L. ;
Yang, Lixing ;
Gordenin, Dmitry ;
Klimczak, Leszek J. ;
Zhang, Cheng-Zhong ;
Pellman, David S. ;
Park, Peter J. ;
Akdemir, Kadir C. ;
Alvarez, Eva G. ;
Baez-Ortega, Adrian ;
Beroukhim, Rameen ;
Boutros, Paul C. ;
Bowtell, David D. L. ;
Brors, Benedikt ;
Burns, Kathleen H. ;
Campbell, Peter J. ;
Chan, Kin ;
Chen, Ken ;
Dueso-Barroso, Ana ;
Dunford, Andrew J. ;
Edwards, Paul A. ;
Estivill, Xavier ;
Etemadmoghadam, Dariush ;
Feuerbach, Lars ;
Fink, J. Lynn ;
Frenkel-Morgenstern, Milana ;
Garsed, Dale W. ;
Gerstein, Mark ;
Gordenin, Dmitry A. ;
Haan, David ;
Haber, James E. ;
Hess, Julian M. ;
Hutter, Barbara ;
Imielinski, Marcin ;
Jones, David T. W. ;
Ju, Young Seok ;
Kazanov, Marat D. ;
Koh, Youngil ;
Korbel, Jan O. ;
Kumar, Kiran ;
Lee, Eunjung Alice ;
Li, Yilong ;
Lynch, Andy G. ;
Macintyre, Geoff ;
Markowetz, Florian ;
Martincorena, Inigo .
NATURE GENETICS, 2020, 52 (03) :331-+
[10]   Combined MEK and STAT3 Inhibition Uncovers Stromal Plasticity by Enriching for Cancer-Associated Fibroblasts With Mesenchymal Stem Cell-Like Features to Overcome Immunotherapy Resistance in Pancreatic Cancer [J].
Datta, Jashodeep ;
Dai, Xizi ;
Bianchi, Anna ;
Silva, Iago De Castro ;
Mehra, Siddharth ;
Garrido, Vanessa T. ;
Lamichhane, Purushottam ;
Singh, Samara P. ;
Zhou, Zhiqun ;
Dosch, Austin R. ;
Messaggio, Fanuel ;
Ban, Yuguang ;
Umland, Oliver ;
Hosein, Peter J. ;
Nagathihalli, Nagaraj S. ;
Merchant, Nipun B. .
GASTROENTEROLOGY, 2022, 163 (06) :1593-1612