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Calreticulin as a potential diagnostic biomarker for lung cancer

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Abstract

Calreticulin (CRT) is an endoplasmic reticulum luminal Ca2+-binding chaperone protein. By immunizing mice with recombinant fragment (rCRT/39-272), six clones of monoclonal antibodies (mAbs) were generated and characterized. Based on these mAbs, a microplate chemiluminescent enzyme immunoassay (CLEIA) system with a measured limit of detection of 0.09 ng/ml was developed. Using this CLEIA system, it was found that soluble CRT (sCRT) level in serum samples from 58 lung cancer patients was significantly higher than that from 40 healthy individuals (only 9 were detectable, P < 0.0001). Among them, serum sCRT in the small cell lung cancer was lower than that in adenocarcinoma (P = 0.0085), while both were lower than that in the squamous cell carcinoma (P = 0.013, P = 0.0012, respectively). Moreover, it was found that sCRT in sera from the patients after chemotherapy was higher than that from the patients without chemotherapy (P = 0.042). Further study by immunohistochemistry showed that CRT was also highly expressed in the cytoplasm and on the membrane of the lung cancer cells, while there was a trace amount of CRT expression in normal lung cells. Correspondingly, the expression level of CRT on lung cancer cell membrane was associated with the tumor pathological grade. This study demonstrates that sCRT concentration in sera of lung cancer patients is higher than that in sera of healthy individuals, and CRT expression level on lung cancer cell membrane is associated with tumor pathological classification and grade. These findings suggest that CRT may be used as a biomarker in lung cancer prediction and diagnosis.

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Abbreviations

CRT:

Calreticulin

CLEIA:

Chemiluminescent enzyme immunoassay

IHC:

Immunohistochemistry

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Acknowledgments

We thank Institute of Biology and Medical Sciences Soochow University (Suzhou, China) for the antigen rCRT39/272. This work was supported by the National Natural Science Foundation of China (30972683 and 31070794).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Immunology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi’an, 710032, China

    Rongrong Liu, Jiuyu Gong, Qi Li, Chaojun Song, Yongming Li, Zhijia Liu, Yun Dong, Lihua Chen & Boquan Jin

  2. Department of Traditional Chinese Medicine, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, China

    Jun Chen

  3. Department of Respiratory Medicine, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, China

    Jian Zhang

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  1. Rongrong Liu
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  2. Jiuyu Gong
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  10. Lihua Chen
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Correspondence to Lihua Chen or Boquan Jin.

Additional information

R. Liu, J. Gong and J. Chen contributed equally to the work.

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Liu, R., Gong, J., Chen, J. et al. Calreticulin as a potential diagnostic biomarker for lung cancer. Cancer Immunol Immunother 61, 855–864 (2012). https://doi.org/10.1007/s00262-011-1146-8

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  • DOI: https://doi.org/10.1007/s00262-011-1146-8

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