A comprehensive analysis of different gene classes in pancreatic cancer: SIGLEC15 may be a promising immunotherapeutic target

被引:4
作者
Xu, Ji-li [1 ]
Guo, Yong [2 ]
机构
[1] Zhejiang Chinese Med Univ, Clin Med Coll 1, Hangzhou, Zhejiang, Peoples R China
[2] Zhejiang Chinese Med Univ, Affiliated Hosp 1, Dept Med Oncol, 54 Youdian Rd, Hangzhou, Zhejiang, Peoples R China
基金
中国国家自然科学基金;
关键词
Pancreatic cancer; Expression; Prognosis; SIGLEC15; Immune escape; WEB SERVER; EXPRESSION; HEDGEHOG; PROLIFERATION; COMPLEXITY; LANDSCAPE; NETWORKS; SURVIVAL; INVASION;
D O I
10.1007/s10637-021-01176-5
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background. Pancreatic cancer (PC) is one of the most lethal cancer types with an extremely poor diagnosis and prognosis. This study aimed to comprehensively analyze the relationships between PC and different gene classes. Methods. Numerous genes from different categories were selected from the UALCAN database. Expression and survival analysis of these genes were performed via GEPIA, starBase and Kaplan-Meier Plotter tools. The correlations between PC-related genes and frequently mutated genes in PC as well as myeloid-derived suppressor cells (MDSCs) infiltration levels were explored by TIMER tool. The associations between PC-related genes, immune checkpoints and 182 core cancer-intrinsic CTLs-evasion genes were analyzed by R software. Besides, KEGG analysis were performed for the PC-related genes. Results. 14 genes were identified to be highly expressed in pancreatic cancer and significantly associated with poor prognosis. Besides, high expression of these genes were observed in patients with KRAS or TP53 mutations. Most genes were significantly positively associated with immune checkpoint SIGLEC15, however, showed negative relations to PDCD1, CTLA4, LAG3, TIGIT, PDCD1LG2. In addition, all 14 genes exhibited close relationships with MDSC infiltration levels and various core cancer-intrinsic CTLs-evasion genes, especially DNTTIP1, FADD, ARF6, BCL2L1, CEP55, GALE, PDCD6IP, and RCE1. We also explored the most related pathways with these genes to further reveal the pathogenesis and metastatic mechanisms of PC. Conclusion. Our study analyzed the relationships between 14 PC-related genes and pancreatic cancer from different angles, which may contribute to a better understanding of unsolved mystery in PC.
引用
收藏
页码:58 / 67
页数:10
相关论文
共 42 条
[1]   Proteolysis: Adaptor, adaptor, catch me a catch [J].
Ades, SE .
CURRENT BIOLOGY, 2004, 14 (21) :R924-R926
[2]   MOST HUMAN CARCINOMAS OF THE EXOCRINE PANCREAS CONTAIN MUTANT C-K-RAS GENES [J].
ALMOGUERA, C ;
SHIBATA, D ;
FORRESTER, K ;
MARTIN, J ;
ARNHEIM, N ;
PERUCHO, M .
CELL, 1988, 53 (04) :549-554
[3]   Siglec-15: an immune system Siglec conserved throughout vertebrate evolution [J].
Angata, Takashi ;
Tabuchi, Yukako ;
Nakamura, Kazunori ;
Nakamura, Mitsuru .
GLYCOBIOLOGY, 2007, 17 (08) :838-846
[4]   Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours [J].
Berman, DM ;
Karhadkar, SS ;
Maitra, A ;
de Oca, RM ;
Gerstenblith, MR ;
Briggs, K ;
Parker, AR ;
Shimada, Y ;
Eshleman, JR ;
Watkins, DN ;
Beachy, PA .
NATURE, 2003, 425 (6960) :846-851
[5]   Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes [J].
Biankin, Andrew V. ;
Waddell, Nicola ;
Kassahn, Karin S. ;
Gingras, Marie-Claude ;
Muthuswamy, Lakshmi B. ;
Johns, Amber L. ;
Miller, David K. ;
Wilson, Peter J. ;
Patch, Ann-Marie ;
Wu, Jianmin ;
Chang, David K. ;
Cowley, Mark J. ;
Gardiner, Brooke B. ;
Song, Sarah ;
Harliwong, Ivon ;
Idrisoglu, Senel ;
Nourse, Craig ;
Nourbakhsh, Ehsan ;
Manning, Suzanne ;
Wani, Shivangi ;
Gongora, Milena ;
Pajic, Marina ;
Scarlett, Christopher J. ;
Gill, Anthony J. ;
Pinho, Andreia V. ;
Rooman, Ilse ;
Anderson, Matthew ;
Holmes, Oliver ;
Leonard, Conrad ;
Taylor, Darrin ;
Wood, Scott ;
Xu, Qinying ;
Nones, Katia ;
Fink, J. Lynn ;
Christ, Angelika ;
Bruxner, Tim ;
Cloonan, Nicole ;
Kolle, Gabriel ;
Newell, Felicity ;
Pinese, Mark ;
Mead, R. Scott ;
Humphris, Jeremy L. ;
Kaplan, Warren ;
Jones, Marc D. ;
Colvin, Emily K. ;
Nagrial, Adnan M. ;
Humphrey, Emily S. ;
Chou, Angela ;
Chin, Venessa T. ;
Chantrill, Lorraine A. .
NATURE, 2012, 491 (7424) :399-405
[6]   Oncogenic pathway signatures in human cancers as a guide to targeted therapies [J].
Bild, AH ;
Yao, G ;
Chang, JT ;
Wang, QL ;
Potti, A ;
Chasse, D ;
Joshi, MB ;
Harpole, D ;
Lancaster, JM ;
Berchuck, A ;
Olson, JA ;
Marks, JR ;
Dressman, HK ;
West, M ;
Nevins, JR .
NATURE, 2006, 439 (7074) :353-357
[7]   Expression of the Receptor Tyrosine Kinase EphA2 Is Increased in Smokers and Predicts Poor Survival in Non-Small Cell Lung Cancer [J].
Brannan, Jennifer M. ;
Dong, Wenli ;
Prudkin, Ludmila ;
Behrens, Carmen ;
Lotan, Reuben ;
Bekele, B. Nebiyou ;
Wistuba, Ignacio ;
Johnson, Faye M. .
CLINICAL CANCER RESEARCH, 2009, 15 (13) :4423-4430
[8]   UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses [J].
Chandrashekar, Darshan S. ;
Bashel, Bhuwan ;
Balasubramanya, Sai Akshaya Hodigere ;
Creighton, Chad J. ;
Ponce-Rodriguez, Israel ;
Chakravarthi, Balabhadrapatruni V. S. K. ;
Varambally, Sooryanarayana .
NEOPLASIA, 2017, 19 (08) :649-658
[9]   Long non-coding RNAs: crucial regulators of gastrointestinal cancer cell proliferation [J].
Chen, Jiaxin ;
Liu, Shuiping ;
Hu, Xiaotong .
CELL DEATH DISCOVERY, 2018, 4
[10]   Integrins in cancer: biological implications and therapeutic opportunities [J].
Desgrosellier, Jay S. ;
Cheresh, David A. .
NATURE REVIEWS CANCER, 2010, 10 (01) :9-22