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CXCL13 expression is prognostic and predictive for postoperative adjuvant chemotherapy benefit in patients with gastric cancer

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Abstract

Background

Chemokine (C-X-C motif) ligand 13 (CXCL13/BLC/BCA-1) is a cytokine from C-X-C chemokine family, which is selectively chemotactic for B cells. Previous research has demonstrated that high CXCL13 expression is correlated to poor prognosis in various cancers. However, the association between CXCL13 expression and gastric cancer is still unclear.

Methods

Intratumoral CXCL13 expression was evaluated by immunohistochemistry using a semi-quantitative method (modified H-score) in a testing set of 214 and a validation set of 227 randomly selected gastric cancer patients resected in 2008 in one institution. The median value was used as the cut-off point. We performed correlative analysis of CXCL-13 expression with clinicopathological variables, Kaplan–Meier analysis for association with overall survival (OS), and multivariate modeling.

Results

High CXCL13 expression was associated with larger tumor diameter and shorter OS. By multivariate analysis, CXCL13 expression was associated with OS independently from clinicopathological factors. Within the T2–4 stage patients group, low CXCL13 expression was associated with longer survival, especially in the subgroup of patients (57.6%) who received adjuvant chemotherapy.

Conclusions

Intratumoral CXCL13 expression appears as an independent prognostic marker for patients after gastric cancer resection. In addition, CXCL13 expression may serve as a predictive biomarker of response to postoperative adjuvant chemotherapy in these patients.

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Abbreviations

Akt:

Protein kinase B, PKB

BCA-1:

B cell attracting chemokine 1

CXCL13:

Chemokine (C-X-C motif) ligand 13

CXCR5:

Chemokine (C-X-C motif) receptor 5

IOD:

Integrated optical density

MMP:

Matrix metalloproteinase

PI3-K:

Phosphatidylinositol 3-kinase

TAMs:

Tumor-associated macrophages

TMA:

Tissue microarray

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Acknowledgements

This study was funded by Grants from National Natural Science Foundation of China (81471621, 81472227, 81501999, 81671628 and 31770851) and Shanghai Sailing Program (17YF1402200). All these study sponsors have no roles in the study design, in the collection, analysis, and interpretation of data.

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Author notes

  1. Yichou Wei, Chao Lin and He Li contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Room 358, Building West 7, 130 Dongan Rd, Shanghai, 200032, China

    Yichou Wei, Zhiying Xu, Jieti Wang & Jiejie Xu

  2. Department of General Surgery, Zhongshan Hospital, Fudan University, Room 1004, Building No.1, 180 Fenglin Rd, Shanghai, 200032, China

    Chao Lin, He Li, Ruochen Li, Hao Liu, Heng Zhang & Hongyong He

Authors
  1. Yichou Wei
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  2. Chao Lin
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  3. He Li
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  4. Zhiying Xu
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  6. Ruochen Li
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  7. Hao Liu
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  9. Hongyong He
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  10. Jiejie Xu
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Contributions

Y. Wei, C. Lin and H. Li: acquisition of data, analysis and interpretation of data, statistical analysis and drafting of the manuscript. Z. Xu, J. Wang, R. Li, H. Liu and H. Zhang: technical and material support. H. He and J. Xu: study concept and design, analysis and interpretation of data, drafting of the manuscript, obtained funding and study supervision. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Hongyong He or Jiejie Xu.

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Wei, Y., Lin, C., Li, H. et al. CXCL13 expression is prognostic and predictive for postoperative adjuvant chemotherapy benefit in patients with gastric cancer. Cancer Immunol Immunother 67, 261–269 (2018). https://doi.org/10.1007/s00262-017-2083-y

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  • DOI: https://doi.org/10.1007/s00262-017-2083-y

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