title: Calreticulin as a potential diagnostic biomarker for lung cancer.
abstract: Calreticulin (CRT) is an endoplasmic reticulum luminal Ca(2+)-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.
authors.affiliation: Department of Immunology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an, China.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Liu
authors.forename: Jiuyu
authors.initials: J
authors.lastname: Gong
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.forename: Chaojun
authors.initials: C
authors.lastname: Song
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Yongming
authors.initials: Y
authors.lastname: Li
authors.forename: Zhijia
authors.initials: Z
authors.lastname: Liu
authors.forename: Yun
authors.initials: Y
authors.lastname: Dong
authors.forename: Lihua
authors.initials: L
authors.lastname: Chen
authors.forename: Boquan
authors.initials: B
authors.lastname: Jin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D014408:Biomarkers, Tumor / Q000097:blood*; D015153:Blotting, Western; D037282:Calreticulin / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000188:drug therapy; D008297:Male; D051379:Mice; D008875:Middle Aged; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D037282:Calreticulin
references.citation: CA Cancer J Clin. 2011 Mar-Apr;61(2):91-112
references.pmid: 21303969
references.citation: Nature. 1997 Apr 24;386(6627):843-7
references.pmid: 9126744
references.citation: FASEB J. 2010 Mar;24(3):665-83
references.pmid: 19940256
references.citation: Ann Oncol. 2005 Feb;16(2):314-21
references.pmid: 15668290
references.citation: Pathol Oncol Res. 2009 Mar;15(1):89-90
references.pmid: 18925427
references.citation: Int J Urol. 2009 May;16(5):481-6
references.pmid: 19389084
references.citation: Cancer Immunol Immunother. 2011 Oct;60(10):1431-7
references.pmid: 21644033
references.citation: EMBO J. 2009 Mar 4;28(5):578-90
references.pmid: 19165151
references.citation: Anal Chem. 2010 Sep 15;82(18):7758-65
references.pmid: 20799707
references.citation: Cell. 2005 Oct 21;123(2):321-34
references.pmid: 16239148
references.citation: Clin Chem. 2004 May;50(5):857-66
references.pmid: 14764641
references.citation: Nat Med. 2007 Jan;13(1):54-61
references.pmid: 17187072
references.citation: J Biol Chem. 2004 Nov 19;279(47):48983-92
references.pmid: 15371459
references.citation: Am J Pathol. 2008 Sep;173(3):610-30
references.pmid: 18753412
references.citation: J Immunol. 2006 Sep 15;177(6):3582-9
references.pmid: 16951317
references.citation: Ann Surg Oncol. 2009 Feb;16(2):524-33
references.pmid: 19050968
references.citation: Tumour Biol. 2009;30(3):121-9
references.pmid: 19506400
references.citation: Proteomics. 2005 Jul;5(10):2602-11
references.pmid: 15924290
references.citation: Neuroendocrinology. 2005;82(1):1-10
references.pmid: 16293970
references.citation: Cancer Epidemiol Biomarkers Prev. 2010 Aug;19(8):1893-907
references.pmid: 20647400
references.citation: Int J Radiat Biol. 2009 Dec;85(12):1126-36
references.pmid: 19995238
references.citation: J Exp Clin Cancer Res. 2009 Feb 24;28:25
references.pmid: 19236728
references.citation: Cell Death Differ. 2008 Feb;15(2):274-82
references.pmid: 18034188
references.citation: J Immunol. 2010 Oct 15;185(8):4561-9
references.pmid: 20855873
references.citation: Cancer Res. 2007 Sep 1;67(17):7941-4
references.pmid: 17804698
references.citation: Curr Opin Immunol. 2008 Oct;20(5):504-11
references.pmid: 18573340
references.citation: J Mol Med (Berl). 2007 Oct;85(10):1069-76
references.pmid: 17891368
references.citation: Cancer Immunol Immunother. 2010 May;59(5):769-77
references.pmid: 19940990
references.citation: Gastroenterology. 2006 Jun;130(7):2010-22
references.pmid: 16762624
references.citation: Trends Cell Biol. 2001 Mar;11(3):122-9
references.pmid: 11306273
references.citation: Sci Transl Med. 2010 Dec 22;2(63):63ra94
references.pmid: 21178137
references.citation: Cell Death Differ. 2007 Oct;14(10):1848-50
references.pmid: 17657249
references.citation: Clin Exp Immunol. 2009 Feb;155(2):207-15
references.pmid: 19040604
references.citation: Mod Pathol. 2010 Dec;23(12):1559-66
references.pmid: 20834237