ASRGL1 Correlates With Immune Cell Infiltration in Hepatocellular Carcinoma and Can Serve as a Prognostic Biomarker

被引:5
作者
Xue, Cailin [1 ]
Gao, Peng [1 ]
Cui, Xiaohan [1 ]
Zhang, Xudong [1 ]
Lei, Jin [1 ]
Li, Renzhi [1 ]
Zhu, Chunfu [1 ]
Qin, Xihu [1 ]
机构
[1] Nanjing Med Univ, Affiliated Changzhou Peoples Hosp 2, Dept Hepatobiliary Surg, Changzhou, Jiangsu, Peoples R China
来源
FRONTIERS IN ONCOLOGY | 2021年 / 11卷
基金
中国国家自然科学基金;
关键词
HCC; ASRGL1; biomarker; immune; immune cell infiltration; ASPARAGINASE-LIKE PROTEIN; GENE-EXPRESSION; WEB SERVER; CANCER; SURVIVAL; CRASH;
D O I
10.3389/fonc.2021.680070
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background The enzyme L-asparaginase (ASRGL1) catalyzes the hydrolysis of L-asparagine (Asn) to L-aspartic acid (Asp) and ammonia. Numerous studies have shown a strong correlation between ASRGL1 expression and tumorigenesis. However, the expression and biological function of ASRGL1 in hepatocellular carcinoma (HCC) are still unclear. Methods We explored the mRNA expression of ASRGL1 in HCC using the HCCDB, Oncomine, and TIMER 2.0 databases. Western blotting and immunohistochemical analyses were also used to determine the mRNA expression of ASRGL1 in HCC. LinkedOmics was used to analyze the genes co-expressed with ASRGL1 and regulators including kinases, miRNAs, and transcription factors. The Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of the co-expressed genes were also investigated using LinkedOmics. The correlation between ASRGL1 expression and immune infiltrates was analyzed using the TIMER 2.0 and Gene Expression Profiling Interactive Analysis (GEPIA) databases. The effects of ASRGL1 expression on patient outcome were investigated using the UALCAN and GEPIA databases, and the Kaplan-Meier plotter. c-Bioportal was used to explore the mutations of ASRGL1 in HCC. Results Compared with the adjacent tissues, ASRGL1 was upregulated in HCC. High ASRGL1 expression in HCC indicated poor relapse-free survival, progression-free survival, disease-specific survival, and overall survival. The expression of ASRGL1 was significantly correlated with infiltrating levels of B cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells in HCC. Conclusion Our findings suggest that ASRGL1 is overexpressed in HCC and that ASRGL1 expression was significantly correlated with immune infiltration in HCC and prognosis. Therefore, ASRGL1 may serve as a biomarker for the early diagnosis and treatment of HCC.
引用
收藏
页数:15
相关论文
共 34 条
  • [1] A novel asparaginase-like protein is a sperm autoantigen in rats
    Bush, LA
    Herr, JC
    Wolkowicz, M
    Sherman, NE
    Shore, A
    Flickinger, CJ
    [J]. MOLECULAR REPRODUCTION AND DEVELOPMENT, 2002, 62 (02) : 233 - 247
  • [2] UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses
    Chandrashekar, Darshan S.
    Bashel, Bhuwan
    Balasubramanya, Sai Akshaya Hodigere
    Creighton, Chad J.
    Ponce-Rodriguez, Israel
    Chakravarthi, Balabhadrapatruni V. S. K.
    Varambally, Sooryanarayana
    [J]. NEOPLASIA, 2017, 19 (08): : 649 - 658
  • [3] Elements of cancer immunity and the cancer-immune set point
    Chen, Daniel S.
    Mellman, Ira
    [J]. NATURE, 2017, 541 (7637) : 321 - 330
  • [4] DKK1 promotes hepatocellular carcinoma cell migration and invasion through β-catenin/MMP7 signaling pathway
    Chen, Liang
    Li, Ming
    Li, Qian
    Wang, Chao-jie
    Xie, Song-qiang
    [J]. MOLECULAR CANCER, 2013, 12
  • [5] Gene expression markers of Tumor Infiltrating Leukocytes
    Danaher, Patrick
    Warren, Sarah
    Dennis, Lucas
    D'Amico, Leonard
    White, Andrew
    Disis, Mary L.
    Geller, Melissa A.
    Odunsi, Kunle
    Beechem, Joseph
    Fling, Steven P.
    [J]. JOURNAL FOR IMMUNOTHERAPY OF CANCER, 2017, 5
  • [6] β-Catenin Activation Promotes Immune Escape and Resistance to Anti-PD-1 Therapy in Hepatocellular Carcinoma
    de Galarreta, Marina Ruiz
    Bresnahan, Erin
    Molina-Sanchez, Pedro
    Lindblad, Katherine E.
    Maier, Barbara
    Sia, Daniela
    Puigvehi, Marc
    Miguela, Vernica
    Casanova-Acebes, Maria
    Dhainaut, Maxime
    Villacorta-Martin, Carlos
    Singhi, Aatur D.
    Moghe, Akshata
    von Felden, Johann
    Grinspan, Lauren Tal
    Wang, Shuang
    Kamphorst, Alice O.
    Monga, Satdarshan P.
    Brown, Brian D.
    Villanueva, Augusto
    Llovet, Josep M.
    Merad, Miriam
    Lujambio, Amaia
    [J]. CANCER DISCOVERY, 2019, 9 (08) : 1124 - 1141
  • [7] Loss of ASRGL1 expression is an independent biomarker for disease-specific survival in endometrioid endometrial carcinoma
    Edqvist, Per-Henrik D.
    Huvila, Jutta
    Forsstrom, Bjorn
    Talve, Lauri
    Carpen, Olli
    Salvesen, Helga B.
    Krakstad, Camilla
    Grenman, Seija
    Johannesson, Henrik
    Ljungqvist, Oscar
    Uhlen, Mathias
    Ponten, Fredrik
    Auranen, Annika
    [J]. GYNECOLOGIC ONCOLOGY, 2015, 137 (03) : 529 - 537
  • [8] Evtimova V, 2004, INT J ONCOL, V24, P33
  • [9] Outcomes of sequential treatment with sorafenib followed by regorafenib for HCC: Additional analyses from the phase III RESORCE trial
    Finn, Richard S.
    Merle, Philippe
    Granito, Alessandro
    Huang, Yi-Hsiang
    Bodoky, Gyorgy
    Pracht, Marc
    Yokosuka, Osamu
    Rosmorduc, Olivier
    Gerolami, Rene
    Caparello, Chiara
    Cabrera, Roniel
    Chang, Charissa
    Sun, Weijing
    LeBerre, Marie-Aude
    Baumhauer, Annette
    Meinhardt, Gerold
    Bruix, Jordi
    [J]. JOURNAL OF HEPATOLOGY, 2018, 69 (02) : 353 - 358
  • [10] Asparaginase-like protein 1 is an independent prognostic marker in primary endometrial cancer, and is frequently lost in metastatic lesions
    Fonnes, Tina
    Berg, Hege F.
    Bredholt, Therese
    Edqvist, Per-Henrik D.
    Sortland, Kristina
    Berg, Anna
    Salvesen, Helga B.
    Akslen, Lars A.
    Werner, Henrica M. J.
    Trovik, Jone
    Tangen, Ingvild L.
    Krakstad, Camilla
    [J]. GYNECOLOGIC ONCOLOGY, 2018, 148 (01) : 197 - 203