Volume 4 Issue 2
Dec.  2020
Turn off MathJax
Article Contents
Pei Chen, Shiwen Wang, Bo Chen, Bing Lu, Xiaojing Zhang, Xiaohui Jiang, Yao Wang. High LIMP2 expression serves as a predictor for improved clinical outcomes in gastric cancer patients[J]. Blood&Genomics, 2020, 4(2): 142-150. doi: 10.46701/BG.2020022020119
Citation: Pei Chen, Shiwen Wang, Bo Chen, Bing Lu, Xiaojing Zhang, Xiaohui Jiang, Yao Wang. High LIMP2 expression serves as a predictor for improved clinical outcomes in gastric cancer patients[J]. Blood&Genomics, 2020, 4(2): 142-150. doi: 10.46701/BG.2020022020119

High LIMP2 expression serves as a predictor for improved clinical outcomes in gastric cancer patients

doi: 10.46701/BG.2020022020119
More Information
  • Corresponding author: Xiaohui Jiang, Department of General Surgery, Nantong Tumor Hospital, 48 Xisi Road, Nantong, Jiangsu 226361, China. E-mail: jxhyjl@163.com; Yao Wang, Department of General Surgery, the Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, Jiangsu 226021, China. E-mail: wangyao@ntu.edu.cn
  • Received Date: 2020-08-20
  • Accepted Date: 2020-12-10
  • Rev Recd Date: 2020-10-27
  • Available Online: 2021-07-01
  • Publish Date: 2020-12-30
  • Lysosomal integral membrane protein-2 (LIMP2) is an important component of innate immunity. However, its role in the anti-tumor response remains unknown. Here, we found that the level of LIMP2 mRNA was frequently upregulated in gastric cancer (GC) tissues according to the TCGA, which was confirmed by immunohistochemistry in 329 cases. LIMP2 expression was significantly associated with Lauren classification (P=0.042), depth of invasion (P=0.016), lymph node metastasis (P=0.039) and TNM stage (P=0.027). LIMP2 expression (P < 0.001), differentiation (P < 0.001), TNM stage (P < 0.001) and preoperative CEA (P=0.018) can be used as independent prognostic factors. GC patients with higher levels of LIMP2 mRNA experienced improved clinical outcomes. Mechanically, the TGF-β signaling pathway, the ERBB signaling pathway, and Toll-like receptor signaling were enriched in proteins with higher LIMP2. Moreover, LIMP2 expression was positively related with M1 tumor-associated macrophages (TAMs) in TCGA data, which was verified by capturing LIMP2 and CD86 co-expression in GC samples. The study suggests that LIMP2 expression in GC would predict improved outcomes with M1 TAMs infiltration.


  • Conflict of interests: All authors have no conflict of interests.
  • loading
  • [1]
    Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6): 394-424. doi: 10.3322/caac.21492
    Van Cutsem E, Sagaert X, Topal B. Haustermans kand prenen H gastric cancer[J]. Lancet, 2016, 388: 2654-2664. doi: 10.1016/S0140-6736(16)30354-3
    Allemani C, Weir HK, Carreira H, et al. Global surveil-lance of cancer survival 1995-2009: analysis of individual data for 25 676 887 patients from 279 population-based registries in 67 countries (CONCORD-2)[J]. Lancet, 2015, 385(9972): 977-1010. doi: 10.1016/S0140-6736(14)62038-9
    Saftig P, Klumperman J. Lysosome biogenesis and lysosomal membrane proteins: trafficking meets function[J]. Nat Rev Mol Cell Biol, 2009, 10(9): 623-635. http://www.nature.com/nrm/journal/v10/n9/fig_tab/nrm2745_F1.html
    Fujita H, Ezaki J, Noguchi Y, et al. Isolation and sequencing of a cDNA clone encoding 85kDa sialogly-coprotein in rat liver lysosomal membranes[J]. Biochem Biophys Res Commun, 1991, 178(2): 444-452. doi: 10.1016/0006-291X(91)90127-S
    Endemann G, Stanton LW, Madden KS, et al. CD36 is a receptor for oxidized low density lipoprotein[J]. J Biol Chem, 1993, 268(16): 11811-11816. doi: 10.1016/S0021-9258(19)50272-1
    Acton SL, Scherer PE, Lodish HF, et al. Expression cloning of SR-BI, a CD36-related class B scavenger receptor[J]. J Biol Chem, 1994, 269(33): 21003-21009. doi: 10.1016/S0021-9258(17)31921-X
    Reczek D, Schwake M, Schröder J, et al. LIMP-2 is a receptor for lysosomal mannose-6-phosphate-independent targeting of beta-glucocerebrosidase[J]. Cell, 2007, 131(4): 770-783. doi: 10.1016/j.cell.2007.10.018
    Kampine JP, Brady RO, Kanfer JN, et al. Diagnosis of gaucher's disease and niemann-pick disease with small samples of venous blood[J]. Science, 1967, 155(3758): 86-88. doi: 10.1126/science.155.3758.86
    Tayebi N, Callahan M, Madike V, et al. Gaucher disease and parkinsonism: A phenotypic and genotypic characterization[J]. Mol Genet Metab, 2001, 73(4): 313-321. doi: 10.1006/mgme.2001.3201
    Aharon-Peretz J, Rosenbaum H Gershoni-Baruch R. Mutations in the glucocerebrosidase gene and Parkinson's disease in Ashkenazi Jews[J]. N Engl J Med, 2004, 351(19): 1972-7. doi: 10.1056/NEJMoa033277
    Yamayoshi S, Yamashita Y, Li J, et al. Scavenger receptor B2 is a cellular receptor for enterovirus 71[J]. Nat Med, 2009, 15(7): 798-801. doi: 10.1038/nm.1992
    Yamayoshi S, Iizuka S, Yamashita T, et al. Human SCARB2-dependent infection by coxsackievirus A7, A14, and A16 and enterovirus 71[J]. J Virol, 2012, 86(10): 5686-5696. doi: 10.1128/JVI.00020-12
    Kuronita T, Eskelinen EL, Fujita H, et al. A role for the lysosomal membrane protein LGP85 in the biogenesis and maintenance of endosomal and lysosomal morphology[J]. J Cell Sci, 2002, 115(Pt 21): 4117-4131. http://www.ncbi.nlm.nih.gov/pubmed/12356916
    Conrad KS, Cheng TW, Ysselstein D, et al. Lysosomal integral membrane protein-2 as a phospholipid receptor revealed by biophysical and cellular studies[J]. Nat Commun, 2017, 8(1): 1908. doi: 10.1038/s41467-017-02044-8
    Berkovic SF, Dibbens LM, Oshlack A, et al. Array-based gene discovery with three unrelated subjects shows SCARB2/LIMP-2 deficiency causes myoclonus epilepsy and glomerulosclerosis[J]. Am J Hum Genet, 2008, 82(3): 673-684. doi: 10.1016/j.ajhg.2007.12.019
    Gamp AC, Tanaka Y, Lüllmann-Rauch R, et al. LIMP-2/LGP85 deficiency causes ureteric pelvic junction obstruction, deafness and peripheral neuropathy in mice[J]. Hum Mol Genet, 2003, 12(6): 631-646. doi: 10.1093/hmg/ddg062
    Johnson IR, Parkinson-Lawrence EJ, Shandala T, et al. Altered endosome biogenesis in prostate cancer has biomarker potential[J]. Mol Cancer Res, 2014, 12(12): 1851-1862. doi: 10.1158/1541-7786.MCR-14-0074
    Pasini FS, Maistro S, Snitcovsky I, et al. Four-gene expression model predictive of lymph node metastases in oral squamous cell carcinoma[J]. Acta Oncol, 2012, 51(1): 77-85. doi: 10.3109/0284186X.2011.620619
    Chen P, Liu C, Li P, et al. High RhCG expression predicts poor survival and promotes migration and proliferation of gastric cancer via keeping intracellular alkaline[J]. Exp Cell Res, 2020, 386(2): 111740. doi: 10.1016/j.yexcr.2019.111740
    Sun MJ, Qi Y, Jin Q, et al. Increased SLC4A11 expression is associated with poor prognosis of gastric cancer[J]. Blood and Genomics, 2020, 4(1): 61-70. doi: 10.46701/BG.2020012019119
    Subramanian A, Tamayo P, Mootha VK, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles[J]. Proc Natl Acad Sci U S A, 2005, 102(43): 15545-15550. doi: 10.1073/pnas.0506580102
    Li T, Fan J, Wang BB, et al. TIMER: A web server for comprehensive analysis of tumor-infiltrating immune cells[J]. Cancer Res, 2017, 77(21): e108-e110. doi: 10.1158/0008-5472.CAN-17-0307
    Tang Z, Li C, Kang B, et al. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses[J]. Nucleic Acids Res, 2017, 45(W1): W98-W102. doi: 10.1093/nar/gkx247
    Carrasco-Marín E, Fernández-Prieto L, Rodriguez-Del RE, et al. LIMP-2 links late phagosomal trafficking with the onset of the innate immune response to Listeria monocytogenes: a role in macrophage activation[J]. J Biol Chem, 2011, 286(5): 3332-3341. doi: 10.1074/jbc.M110.146761
    Savas P, Salgado R, Denkert C, et al. Clinical relevance of host immunity in breast cancer: from TILs to the clinic[J]. Nat Rev Clin Oncol, 2016, 13(4): 228-241. doi: 10.1038/nrclinonc.2015.215
    Kalkman HO, Feuerbach D. Antidepressant therapies inhibit inflammation and microglial M1-polarization[J]. Pharmacol Ther, 2016, 163: 82-93. doi: 10.1016/j.pharmthera.2016.04.001
    Biswas SK, Mantovani A. Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm[J]. Nat Immunol, 2010, 11(10): 889-896. doi: 10.1038/ni.1937
    Hardbower DM, Singh K, Asim M, et al. EGFR regu-lates macrophage activation and function in bacterial infection[J]. J Clin Invest, 2016, 126(9): 3296-3312. doi: 10.1172/JCI83585
    Zhao G, Liu L, Peek RJ, et al. Activation of epidermal growth factor receptor in macrophages mediates feedback inhibition of M2 polarization and gastrointestinal tumor cell growth[J]. J Biol Chem, 2016, 291(39): 20462-20472. doi: 10.1074/jbc.M116.750182
  • 加载中


    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(6)  / Tables(2)

    Article Metrics

    Article views (22) PDF downloads(0) Cited by()
    Proportional views


    DownLoad:  Full-Size Img  PowerPoint