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CXCL12 chemokine and CXCR4 receptor: association with susceptibility and prognostic markers in triple negative breast cancer

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Abstract

CXCL12/CXCR4 signaling has been implicated in breast carcinogenesis, and genetic polymorphisms in these molecules have been associated with different types of cancer. The present study analyzed genetic polymorphisms in CXCL12 (rs1801157, G > A) and CXCR4 (rs2228014, C > T) and CXCR4 immunostaining in tumor tissues from patients with triple negative breast cancer (TNBC) aiming to evaluate their possible role in its’ susceptibility and prognosis. Genetic polymorphisms were analyzed in 59 TNBC patients and 150 control women; age-adjusted logistic regression showed no association when variants were considered in isolation; however, a statistically significant interaction was noted for heterozygosis for both allelic variants increasing the odds for TNBC (CXCL12-GA by CXCR4-CT: OR 7.23; 95% CI 1.15–45.41; p = 0.035). CXCL12 polymorphism was correlated negatively with proliferation index (Ki67) (Tau-b = − 0.406; p = 0.006). CXCR4 immunostaining was evaluated in 37 TNBC patients (22 with paired tumor-normal adjacent tissue). CXCR4 was detected more intensely in cell cytoplasm than in membrane, and was more expressed in tumor than in normal adjacent tissues, although not statistically significant. CXCR4 expression on the membrane of tumor cells was correlated positively with histopathological grade (Tau-b = 0.271; p = 0.036) and negatively with lymph node metastasis (Tau-b = − 0.478; p = 0.036). The present study indicates that CXCL12 and CXCR4 polymorphisms and CXCR4 immunostaining might have susceptibility and prognostic roles in TNBC pathogenesis.

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Acknowledgements

We acknowledge all the volunteer donors involved in the study and the Londrina State University Clinical Hospital (HC-UEL), Orlando Sestari primary health care unit and Londrina Cancer Hospital (HCL) staff for support during sample collection. The present study was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq 303186/2015-1 process), Fundação Araucária (1027/2013 agreement) and Coordenadoria de Pós-Graduação, Londrina State University - PROPPG-UEL.

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  1. Department of Pathology, Clinical and Toxicological Analyses, Health Sciences Center, Londrina State University, Londrina, Parana, Brazil

    Alda Losi Guembarovski & Edna Maria Vissoci Reiche

  2. Department of General Biology, Biological Sciences Center, Londrina State University, Londrina, Parana, Brazil

    Roberta Losi Guembarovski

  3. Department of Pathological Sciences, Biological Sciences Center, Londrina State University, Londrina, Parana, Brazil

    Bruna Karina Banin Hirata, Glauco Akelinghton Freire Vitiello, Karen Mayumi Suzuki, Mayara Tiemi Enokida & Maria Angelica Ehara Watanabe

  4. Laboratory of Studies and Applications of DNA Polymorphisms, Biological Sciences Center, Londrina State University, Rodovia Celso Garcia Cid, Pr 445 Km 380, Campus Universitário, Londrina, Parana, CEP 86.057-970, Brazil

    Roberta Losi Guembarovski

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Guembarovski, A.L., Guembarovski, R.L., Hirata, B.K.B. et al. CXCL12 chemokine and CXCR4 receptor: association with susceptibility and prognostic markers in triple negative breast cancer. Mol Biol Rep 45, 741–750 (2018). https://doi.org/10.1007/s11033-018-4215-7

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