Integrating single-cell analysis and machine learning to create glycosylation-based gene signature for prognostic prediction of uveal melanoma

被引:43
作者
Liu, Jianlan [1 ]
Zhang, Pengpeng [2 ]
Yang, Fang [3 ]
Jiang, Keyu [1 ]
Sun, Shiyi [1 ]
Xia, Zhijia [4 ]
Yao, Gang [1 ]
Tang, Jian [1 ]
机构
[1] Nanjing Med Univ, Affiliated Hosp 1, Dept Plast & Burns Surg, Nanjing, Peoples R China
[2] Nanjing Med Univ, Affiliated Hosp 1, Dept Thorac Surg, Nanjing, Peoples R China
[3] Charite Univ Med Berlin, Campus Virchow Klinikum, Dept Ophthalmol, Berlin, Germany
[4] Ludwig Maximilians Univ Munchen, Dept Gen Visceral & Transplant Surg, Munich, Germany
关键词
glycosylation; uveal melanoma; immunotherapy; machine learning; AUP1; PROTEIN GLYCOSYLATION; MECHANISMS;
D O I
10.3389/fendo.2023.1163046
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BackgroundIncreasing evidence suggests a correlation between glycosylation and the onset of cancer. However, the clinical relevance of glycosylation-related genes (GRGs) in uveal melanoma (UM) is yet to be fully understood. This study aimed to shed light on the impact of GRGs on UM prognosis. MethodsTo identify the most influential genes in UM, we employed the AUCell and WGCNA algorithms. The GRGs signature was established by integrating bulk RNA-seq and scRNA-seq data. UM patients were separated into two groups based on their risk scores, the GCNS_low and GCNS_high groups, and the differences in clinicopathological correlation, functional enrichment, immune response, mutational burden, and immunotherapy between the two groups were examined. The role of the critical gene AUP1 in UM was validated through in vitro and in vivo experiments. ResultsThe GRGs signature was comprised of AUP1, HNMT, PARP8, ARC, ALG5, AKAP13, and ISG20. The GCNS was a significant prognostic factor for UM, and high GCNS correlated with poorer outcomes. Patients with high GCNS displayed heightened immune-related characteristics, such as immune cell infiltration and immune scores. In vitro experiments showed that the knockdown of AUP1 led to a drastic reduction in the viability, proliferation, and invasion capability of UM cells. ConclusionOur gene signature provides an independent predictor of UM patient survival and represents a starting point for further investigation of GRGs in UM. It offers a novel perspective on the clinical diagnosis and treatment of UM.
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页数:17
相关论文
共 49 条
[1]  
Aibar S, 2017, NAT METHODS, V14, P1083, DOI [10.1038/nmeth.4463, 10.1038/NMETH.4463]
[2]   The importance of immune checkpoints in immune monitoring: A future paradigm shift in the treatment of cancer [J].
Alemohammad, Hajar ;
Najafzadeh, Basira ;
Asadzadeh, Zahra ;
Baghbanzadeh, Amir ;
Ghorbaninezhad, Farid ;
Najafzadeh, Arezoo ;
Safarpour, Hossein ;
Bernardini, Renato ;
Brunetti, Oronzo ;
Sonnessa, Margherita ;
Fasano, Rossella ;
Silvestris, Nicola ;
Baradaran, Behzad .
BIOMEDICINE & PHARMACOTHERAPY, 2022, 146
[3]   Neoadjuvant relatlimab and nivolumab in resectable melanoma [J].
Amaria, Rodabe N. ;
Postow, Michael ;
Burton, Elizabeth M. ;
Tezlaff, Michael T. ;
Ross, Merrick, I ;
Torres-Cabala, Carlos ;
Glitza, Isabella C. ;
Duan, Fei ;
Milton, Denai R. ;
Busam, Klaus ;
Simpson, Lauren ;
McQuade, Jennifer L. ;
Wong, Michael K. ;
Gershenwald, Jeffrey E. ;
Lee, Jeffrey E. ;
Goepfert, Ryan P. ;
Keung, Emily Z. ;
Fisher, Sarah B. ;
Betof-Warner, Allison ;
Shoushtari, Alexander N. ;
Callahan, Margaret ;
Coit, Daniel ;
Bartlett, Edmund K. ;
Bello, Danielle ;
Momtaz, Parisa ;
Nicholas, Courtney ;
Gu, Aidi ;
Zhang, Xuejun ;
Korivi, Brinda Rao ;
Patnana, Madhavi ;
Patel, Sapna P. ;
Diab, Adi ;
Lucci, Anthony ;
Prieto, Victor G. ;
Davies, Michael A. ;
Allison, James P. ;
Sharma, Padmanee ;
Wargo, Jennifer A. ;
Ariyan, Charlotte ;
Tawbi, Hussein A. .
NATURE, 2022, 611 (7934) :155-+
[4]   Targeting Epigenetic Modifications in Uveal Melanoma [J].
Baradaran, Pooneh Chokhachi ;
Kozovska, Zuzana ;
Furdova, Alena ;
Smolkova, Bozena .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2020, 21 (15)
[5]   Future perspectives of uveal melanoma blood based biomarkers [J].
Beasley, Aaron B. ;
Chen, Fred K. ;
Isaacs, Timothy W. ;
Gray, Elin S. .
BRITISH JOURNAL OF CANCER, 2022, 126 (11) :1511-1528
[6]   Uveal melanoma pathobiology: Metastasis to the liver [J].
Bustamante, Prisca ;
Piquet, Leo ;
Landreville, Solange ;
Burnier, Julia, V .
SEMINARS IN CANCER BIOLOGY, 2021, 71 :65-85
[7]   Uveal melanoma: From diagnosis to treatment and the science in between [J].
Chattopadhyay, Chandrani ;
Kim, Dae Won ;
Gombos, Dan S. ;
Oba, Junna ;
Qin, Yong ;
Williams, Michelle D. ;
Esmaeli, Bita ;
Grimm, Elizabeth A. ;
Wargo, Jennifer A. ;
Woodman, Scott E. ;
Patel, Sapna P. .
CANCER, 2016, 122 (15) :2299-2312
[8]   AUP1 regulates lipid metabolism and induces lipid accumulation to accelerate the progression of renal clear cell carcinoma [J].
Chen, Chen ;
Zhao, Wei ;
Lu, Xingxing ;
Ma, Yunbo ;
Zhang, Peizhi ;
Wang, Zicheng ;
Cui, Zilian ;
Xia, Qinghua .
CANCER SCIENCE, 2022, 113 (08) :2600-2615
[9]   Natural killer cell-related prognosis signature characterizes immune landscape and predicts prognosis of HNSCC [J].
Chi, Hao ;
Xie, Xixi ;
Yan, Yingjie ;
Peng, Gaoge ;
Strohmer, Dorothee Franziska ;
Lai, Guichuan ;
Zhao, Songyun ;
Xia, Zhijia ;
Tian, Gang .
FRONTIERS IN IMMUNOLOGY, 2022, 13
[10]   Targeted Therapy of Uveal Melanoma: Recent Failures and New Perspectives [J].
Croce, Michela ;
Ferrini, Silvano ;
Pfeffer, Ulrich ;
Gangemi, Rosaria .
CANCERS, 2019, 11 (06)