Back
 Health  Vol.10 No.1 , January 2018
Study on the Relationship between Expression of LGR5 and Clinicopathological Characteristics in Gastric Cancer Patients
Abstract: The aim of the study was to clarify the role of LGR5 in the process of formation and development of gastric cancer. The expression of LGR5 in gastric cancer and corresponding non-cancerous gastric tissues of 52 gastric cancer patients was assessed with the real-time fluorescence quantitative polymerase chain reaction (RT-PCR) and immunohistochemistry. We also analyzed the relationship between the expression level and clinicopathological characteristics. LGR5 gene and protein expression in gastric cancer tissues was in both cases significantly higher than in corresponding non-cancerous gastric tissues (both P < 0.05), but no significant relationship was found with clinicopathological parameters including tumor location, depth of invasion, differentiation, lymph node metastasis, stage, gender, age and carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9) level in peripheral blood pre-operation of patients (P > 0.05, respectively). Furthermore, LGR5 gene expression was markedly higher in gastric cancer tissues of Helicobacter pylori (HP)-positive patients than negative ones (P < 0.05). The result of the study showed that LGR5 might play a significant role in the process of formation and development of gastric cancer as an oncogene. Its effect might be strengthened by HP infection.
Cite this paper: Xu, X. , Lv, Q. , Xie, P. , Wei, S. and Wang, C. (2018) Study on the Relationship between Expression of LGR5 and Clinicopathological Characteristics in Gastric Cancer Patients. Health, 10, 159-169. doi: 10.4236/health.2018.101013.
References

[1]   Hsu, S.Y., et al. (1998) Characterization of Two LGR Genes Homologous to Gonadotropin and Thyrotropin Receptors with Extracellular Leucine-Rich Repeats and a G Protein-Coupled, Seven Transmembrane Region. Molecular Endocrinology, 12, 1830-1845.
https://doi.org/10.1210/mend.12.12.0211

[2]   Mcdonald, T., et al. (1998) Identification and Cloning of an Orphan G Protein-Coupled Receptor of the Glycoprotein Hormone Receptor Subfamily. Biochemical and Biophysical Research Communication, 247, 266-270.
https://doi.org/10.1006/bbrc.1998.8774

[3]   McClanahan, T., Koseoglu, S., Smith, K., et al. (2006) Identification of Over Expression of Orphan G Protein-Coupled Receptor GPR49 in Human Colon and Ovarian Primary Tumors. Cancer Biology & Therapy, 5, 419-426.
https://doi.org/10.4161/cbt.5.4.2521

[4]   Yamamoto, Y., Sakamoto, M., Fujii, G., et al. (2003) Over Expression of Orphan G-Protein-Coupled Receptor, Gpr49, in Human Hepatocellular Carcinomas with Beta-Catenin Mutations. Hepatology, 37, 528-533.
https://doi.org/10.1053/jhep.2003.50029

[5]   Katoh, M. (2007) Networking of WNT, FGF, Notch, BMP, and Hedgehog Signaling Pathways during Carcinogenesis. Stem Cell Reviews, 3, 30-38.
https://doi.org/10.1007/s12015-007-0006-6

[6]   Wang, X.-Y. (2010) Expression of Wnt1, β-Catenin and Lgr5 in Gastric Lesions and Their Correlation. Dalian Medical University, Dalian.

[7]   Wu, J.P., Qiu, F.Z., Wu, M.C., et al. (2008) Huang Jia Si Surgery. 7th Edition, People’s Health Publishing House, Beijing, 1450.

[8]   NCCN Clinical Practice Guidelines in Oncology Gastric Cancer (Including Cancer in the Proximal 5 cm of the Stomach). NCCN Guidelines.

[9]   Che, X.B. and Liu, W.Z. (2002) Evaluation of Common Diagnostic Methods for Helicobacter pylori. Chinese Journal of Digestion, 22, 691-693.

[10]   Simon, E., Petke, D. and Boger, C. (2012) The Spatial Distribution of LGR5+ Cells Correlates with Gastric Cancer Progression. PLoS ONE, 7, e35486:1-15.
https://doi.org/10.1371/journal.pone.0035486

[11]   Bjerknes, M. and Cheng, H. (2002) Multipotential Stem Cells in Adult Mouse Gastric Epithelium. American Journal of Physiology-Gastrointestinal and Liver Physiology, 283, G767-G777.
https://doi.org/10.1152/ajpgi.00415.2001

[12]   Qiao, X.T., Ziel, J.W., McKimpson, W., et al. (2007) Prospective Identification of a Multilineage Progenitor in Murine Stomach Epithelium. Gastroenterology, 133, 1989-1998.
https://doi.org/10.1053/j.gastro.2007.09.031

[13]   Barker, N., van-Es, J.H., Kuipers, J., et al. (2007) Identification of Stem Cells in Small Intestine and Colon by Marker Gene Lgr5. Nature, 449, 1003-1007.
https://doi.org/10.1038/nature06196

[14]   Barker, N., Huch, M., Kujala, P., et al. (2010) Lgr5 Vesem Cells Drive Self Renewal in the Stomach and Build Long Lived Gastric Units in Vitro. Cell Stem Cell, 6, 25-36. https://doi.org/10.1038/nature06196

[15]   Qiao, X.T. and Gumucio, D.L. (2011) Current Molecular Markers for Gastric Progenitor Cells and Gastric Cancer Stem Cells. Journal of Gastroenterology, 46, 855-865.
https://doi.org/10.1007/s00535-011-0413-y

[16]   Becker, L. (2008) Immunostaining of Lgr5, an Intestinal Stem Cell Marker, in Normal and Premalignant Human Gastrointestinal Tissue. Scientific World Journal, 8, 1168-1176.
https://doi.org/10.1100/tsw.2008.148

[17]   Simon, E., Petke, D., Boger, C., et al. (2012) The Spatial Distribution of LGR5+ Cells Correlates with Gastric Cancer Progression. PLoS ONE, 7, e35486.
https://doi.org/10.1371/journal.pone.0035486

[18]   Yamanoi, K., Fukuma, M., Uchida, H., et al. (2013) Over Expression of Leucine-Rich Repeat-Containing G Protein-Coupled Receptor 5 in Gastric Cancer. Pathology International, 63, 13-19.
https://doi.org/10.1111/pin.12013

[19]   Bu, Z., Zheng, Z., Zhang, L., et al. (2013) LGR5 Is a Promising Biomarker for Patients with Stage I and II Gastric Cancer. Chinese Journal of Cancer Research, 25, 79-89.

[20]   Gisbert, J.P. (2011) Helicobacter pylori-Related Diseases: Dyspepsia, Ulcers and Gastric Cancer. Gastroenterology & Hepatology, 34, 15-26.
https://doi.org/10.1016/S0210-5705(11)70017-6

[21]   Zhang, Q.Y. and Li, Q. (2006) Abdominal Surgery. People’s Health Publishing House, Beijing, 157-161.

[22]   Weck, M.N., Gao, L. and Brenner, H. (2009) Helicobacter pylori Infection Anchronic Atrophic Gastritis: Associations According to Severity of Disease. Epidemiology, 20, 569-574.
https://doi.org/10.1097/EDE.0b013e3181a3d5f4

[23]   Ohata, H., Kitauchi, S., Yoshimura, N., et al. (2004) Progression of Chronic Atrophic Gastritis Associated with Helicobacter pylori Infection Increases Risk of Gastric Cancer. International Journal of Cancer, 109, 138-143.
https://doi.org/10.1002/ijc.11680

[24]   Uehara, T., Ma, D., Yao, Y., et al. (2013) H. pylori Infection Is Associated with DNA Damage of Lgr5-Positive Epithelial Stem Cells in the Stomach of Patients with Gastric Cancer. Digestive Diseases and Sciences, 58, 140-149.
https://doi.org/10.1007/s10620-012-2360-8

[25]   Zhang, Y.L., Xue, Y.W., Lan, X.W., et al. (2010) Research on the Prognostic Value of Tumor Markers CA19-9 and CEA in Gastric Cancer Metastasis and Prognosis. Journal of Harbin Medical University, 44, 181-184, 188.

[26]   Ucar, E., Semerci, E., Ustun, H., et al. (2008) Prognostic Value of Preoperative CEA, CA19-9, CA72-4, and AFP Levels in Gastric Cancer. Advances in Therapy, 25, 1075-1084.
https://doi.org/10.1007/s12325-008-0100-4

 
 
Top