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LGR4 and LGR6 are differentially expressed and of putative tumor biological significance in gastric carcinoma

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Abstract

Gastric cancer (GC) is one of the most common causes of cancer-related deaths worldwide. We investigated the differential expression and putative tumor biological significance of five G-protein-coupled receptors (GPCRs) in GC, i.e., LGR4, LGR6, GPR34, GPR160, and GPR171. Based on our previous microarray analyses, we identified five candidate genes in human GC samples. Real-time RT-PCR was carried out to validate their expression in malignant and non-malignant tissues on an independent collective comprising 32 GC patients with and without lymph node metastases. Selected protein targets LGR4 and LGR6 were further validated on paraffin-embedded sections of ten intestinal and ten poorly cohesive (diffuse)-type GCs and their corresponding non-malignant tissue using immunohistochemistry. Additionally, the putative tumor biological significance of LGR4 and LGR6 was studied using tissue microarrays obtained from a cohort of 481 GC patients. On transcriptional level, GPR34, GPR160, and GPR171 were not differentially expressed in GC compared with non-neoplastic mucosa. LGR4 and LGR6 were up-regulated on transcriptional (real-time RT-PCR) and translational (immunohistochemistry) levels in GC. Furthermore, in tissue microarray analysis, LGR6 expression was significantly associated with local tumor growth (T-category; p = 0.04) and correlated with patient survival. LGR4 expression was significantly correlated with nodal spread (N-category; p = 0.025). Our systematic analysis indicates that LGR4 and LGR6 may play a role in GC biology. Future studies will have to demonstrate whether these are also putative diagnostic, prognostic, and/or therapeutic targets for GC.

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Acknowledgments

We would like to thank Sandra Krüger for her excellent technical support. This study was supported by grants from Deutsche Forschungsgemeinschaft (Ro 1173/12).

Conflict of interest

The authors declare that they have no conflict of interest.

Disclosures

There are no potential conflicts (financial, professional, or personal) to disclose that are relevant to the manuscript.

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Authors and Affiliations

  1. Institute of Pathology, Christian-Albrechts-University, Kiel, Germany

    Jan Simon Steffen, Eva Simon, Viktoria Warneke, Katharina Balschun & Christoph Röcken

  2. Department of Medicine II, Faculty of Clinical Medicine Mannheim, University of Heidelberg, Mannheim, Germany

    Matthias Ebert

  3. Department of Pathology, Christian-Albrechts-University, Arnold-Heller-Str. 3/14, 24105, Kiel, Germany

    Christoph Röcken

Authors
  1. Jan Simon Steffen
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  2. Eva Simon
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  6. Christoph Röcken
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Correspondence to Christoph Röcken.

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Online Resource 1

Assessment of LGR4/LGR6-co-expression in tissue micro arrays and correlation with clinico-pathological patient characteristics. P-values were calculated with Fisher's exact test (PDF 165 kb)

Online Resource 2

Patient survival of the cases co-expressing LGR4 and LGR6 compared to those negative for both markers. Results are presented as Kaplan–Meier-curves. The p-value was calculated using the log-rank (Mantel–Cox) test (JPEG 40 kb)

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Steffen, J.S., Simon, E., Warneke, V. et al. LGR4 and LGR6 are differentially expressed and of putative tumor biological significance in gastric carcinoma. Virchows Arch 461, 355–365 (2012). https://doi.org/10.1007/s00428-012-1292-1

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  • DOI: https://doi.org/10.1007/s00428-012-1292-1

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