title: Soluble Human Epidermal Growth Factor Receptor 2 (sHER2) as a Potential Risk Assessment, Screening, and Diagnostic Biomarker of Lung Adenocarcinoma.
abstract: Lung cancer is the leading cause of cancer-related death in the United States. Here, we evaluated the potential clinical utility of soluble human epidermal growth factor receptor 2 (sHER2) for the risk assessment, screening, and diagnosis of non-small cell lung cancer (NSCLC) using an unmatched case-control study design. Serum sHER2 concentrations were measured by immunoassay in 244 primary NSCLC cases and 218 healthy controls. Wilcoxon rank-sum tests, logistic regression models, and receiver operating characteristic plots were used to assess whether sHER2 is associated with lung cancer. Median serum sHER2 concentrations are higher in patients with adenocarcinoma than squamous cell carcinoma regardless of gender, and sHER2 is a weak, independent biomarker of adenocarcinoma, but not of squamous cell carcinoma, adjusted for age and gender. The age-adjusted relative risk (odds) of adenocarcinoma is 3.95 (95% CI: 1.22, 12.81) and 7.93 (95% CI: 2.26, 27.82) greater for women and men with high sHER2 concentrations (≥6.60 ng/mL) vs. low sHER2 concentrations (≤1.85 ng/mL), respectively. When adjusted for each other, sHER2, age, and gender discern healthy controls from patients with primary adenocarcinomas of the lung with 85.9% accuracy. We conclude that even though serum sHER2 is not a strong, stand-alone discriminatory biomarker of adenocarcinoma, sHER2 may be a useful, independent covariate in multivariate risk assessment, screening, and diagnostic models of lung cancer.
authors.affiliation: Department of Preventive Medicine, Northwestern University Biomedical Informatics Center, NUCATS 750 N. Lake Shore Dr., 11th Floor, Chicago, IL 60611, USA. a-cosentino-boehm@northwestern.edu.
authors.forename: Abby L
authors.initials: AL
authors.lastname: Cosentino-Boehm
authors.affiliation: Mayo Clinic Cancer Center, Mayo Clinic, 200 First Street S.W., Rochester, MN 55905, USA. lafky.jacqueline@mayo.edu.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Lafky
authors.affiliation: Mayo Clinic Cancer Center, Mayo Clinic, 200 First Street S.W., Rochester, MN 55905, USA. greenwood.tammy@mayo.edu.
authors.forename: Tammy M
authors.initials: TM
authors.lastname: Greenwood
authors.affiliation: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Kentucky, Lucille P. Markey Cancer Center, Lexington, KY 40536, USA. kdkimb2@email.uky.edu.
authors.forename: Kimberly D
authors.initials: KD
authors.lastname: Kimbler
authors.affiliation: Department of Family Medicine, University of Kentucky, College of Medicine, 800 Rose Street, Lexington, KY 40536 ,USA. marites.buenafe@eku.edu.
authors.forename: Marites C
authors.initials: MC
authors.lastname: Buenafe
authors.affiliation: University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA. wyerliang@yahoo.com.
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR 97331, USA. adam.branscum@oregonstate.edu.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Branscum
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, 200 First Street S.W., Rochester, MN 55905, USA. yang.ping@mayo.edu.
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, P.O. Box 2068063, New Haven, CT 06520 ,USA. nita.maihle@yale.edu.
authors.forename: Nita J
authors.initials: NJ
authors.lastname: Maihle
authors.affiliation: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Kentucky, Lucille P. Markey Cancer Center, Lexington, KY 40536, USA. abaro2@uky.edu.|Department of Epidemiology, University of Kentucky, College of Public Health, 111 Washington Avenue, Lexington, KY 40536, USA. abaro2@uky.edu.
authors.forename: Andre T
authors.initials: AT
authors.lastname: Baron
keywords: adenocarcinoma; diagnosis; early detection; non-small cell lung cancer; risk assessment; screening; soluble human epidermal growth factor receptor 2 (sHER2); squamous cell carcinoma (SCC)
references.citation: Cancer Res. 1999 Mar 15;59(6):1196-201
references.pmid: 10096547
references.citation: Proc Natl Acad Sci U S A. 1999 Sep 14;96(19):10869-74
references.pmid: 10485918
references.citation: Cancer Lett. 2000 Apr 28;152(1):87-95
references.pmid: 10754210
references.citation: BMJ. 2000 Aug 5;321(7257):323-9
references.pmid: 10926586
references.citation: Anticancer Res. 2000 May-Jun;20(3B):2091-6
references.pmid: 10928158
references.citation: Control Clin Trials. 2000 Dec;21(6 Suppl):251S-272S
references.pmid: 11189683
references.citation: Control Clin Trials. 2000 Dec;21(6 Suppl):273S-309S
references.pmid: 11189684
references.citation: J Urol. 2001 Oct;166(4):1514-9
references.pmid: 11547123
references.citation: J Clin Oncol. 2001 Sep 15;19(18 Suppl):83S-86S
references.pmid: 11560979
references.citation: Cancer Detect Prev. 2002;26(1):64-8
references.pmid: 12088205
references.citation: Chest. 2002 Jul;122(1):15-20
references.pmid: 12114333
references.citation: Hematol Oncol Clin North Am. 2002 Oct;16(5):1041-63
references.pmid: 12512382
references.citation: Chest. 2003 Jan;123(1 Suppl):72S-82S
references.pmid: 12527566
references.citation: Chest. 2003 Jan;123(1 Suppl):83S-88S
references.pmid: 12527567
references.citation: Eur Respir J Suppl. 2003 Jan;39:36s-44s
references.pmid: 12572700
references.citation: J Natl Cancer Inst. 2003 Mar 19;95(6):470-8
references.pmid: 12644540
references.citation: Anticancer Res. 2003 Jan-Feb;23(1A):49-62
references.pmid: 12683352
references.citation: Methods Mol Biol. 2003;224:149-57
references.pmid: 12710672
references.citation: Mol Carcinog. 1992;5(3):213-8
references.pmid: 1350198
references.citation: Clin Cancer Res. 2003 Sep 1;9(10 Pt 1):3645-52
references.pmid: 14506153
references.citation: Cancer Epidemiol Biomarkers Prev. 2003 Oct;12(10):987-93
references.pmid: 14578133
references.citation: Clin Cancer Res. 2003 Nov 1;9(14):5238-43
references.pmid: 14614004
references.citation: Lung Cancer. 2004 Apr;44(1):99-110
references.pmid: 15013588
references.citation: Curr Opin Pulm Med. 2004 Jul;10(4):242-7
references.pmid: 15220746
references.citation: Eur J Cancer Prev. 2004 Oct;13(5):425-36
references.pmid: 15452456
references.citation: Bull Cancer. 2005 Feb;92(2):E13-8
references.pmid: 15749638
references.citation: Nihon Rinsho. 2005 Mar;63(3):434-40
references.pmid: 15773342
references.citation: J Natl Cancer Inst. 2005 May 18;97(10):715-23
references.pmid: 15900041
references.citation: Chest. 2005 Jul;128(1):452-62
references.pmid: 16002972
references.citation: BMC Cancer. 2005 Jul 20;5:83
references.pmid: 16029516
references.citation: Environ Health Perspect. 2005 Oct;113(10):1285-90
references.pmid: 16203235
references.citation: J Natl Cancer Inst. 2005 Dec 21;97(24):1832-9
references.pmid: 16368945
references.citation: J Natl Cancer Inst. 2006 May 3;98(9):637-40
references.pmid: 16670389
references.citation: J Biol Chem. 1991 Jan 25;266(3):1716-20
references.pmid: 1671042
references.citation: Int J Cancer. 1991 Oct 21;49(4):616-23
references.pmid: 1680817
references.citation: Eur J Cancer. 1991;27(11):1372-5
references.pmid: 1683776
references.citation: Clin Cancer Res. 2006 Jul 15;12(14 Pt 2):4377s-4383s
references.pmid: 16857814
references.citation: Clin Cancer Res. 2006 Jul 15;12(14 Pt 2):4436s-4440s
references.pmid: 16857824
references.citation: Int J Cancer. 2007 Jan 1;120(1):1-6
references.pmid: 17058200
references.citation: Am J Epidemiol. 2007 Apr 15;165(8):874-81
references.pmid: 17244633
references.citation: J Natl Cancer Inst. 2007 May 2;99(9):715-26
references.pmid: 17470739
references.citation: Br J Cancer. 2008 Jan 29;98(2):270-6
references.pmid: 18087271
references.citation: Rev Recent Clin Trials. 2006 Jan;1(1):1-13
references.pmid: 18393776
references.citation: Cancer Prev Res (Phila). 2008 Sep;1(4):226-8
references.pmid: 19138964
references.citation: Cancer Prev Res (Phila). 2008 Sep;1(4):250-4
references.pmid: 19138968
references.citation: Cancer Prev Res (Phila). 2008 Sep;1(4):255-65
references.pmid: 19138969
references.citation: Cancer Causes Control. 2009 Aug;20(6):877-86
references.pmid: 19277882
references.citation: J Thorac Oncol. 2009 Jun;4(6):697-701
references.pmid: 19318995
references.citation: J Natl Cancer Inst. 2009 Aug 5;101(15):1039-41
references.pmid: 19638503
references.citation: Oncogene. 2009 Aug;28 Suppl 1:S32-7
references.pmid: 19680294
references.citation: Oncogene. 2009 Aug;28 Suppl 1:S38-45
references.pmid: 19680295
references.citation: Cancer Res. 1990 Jul 1;50(13):3947-51
references.pmid: 1972345
references.citation: Oncogene. 1990 Jul;5(7):1001-6
references.pmid: 1973827
references.citation: Nat Biotechnol. 2010 Feb;28(2):117-9
references.pmid: 20139941
references.citation: CA Cancer J Clin. 2010 Sep-Oct;60(5):277-300
references.pmid: 20610543
references.citation: CA Cancer J Clin. 2012 Jan-Feb;62(1):10-29
references.pmid: 22237781
references.citation: Biomarkers. 1996;1(2):141-3
references.pmid: 23888925
references.citation: Per Med. 2005 Nov;2(4):301-315
references.pmid: 29788579
references.citation: Chest. 1995 Jul;108(1):157-62
references.pmid: 7606952
references.citation: Biochim Biophys Acta. 1994 Dec 30;1198(2-3):165-84
references.pmid: 7819273
references.citation: Gynecol Oncol. 1994 Dec;55(3 Pt 1):421-6
references.pmid: 7835782
references.citation: Int J Cancer. 1994 Feb 1;56(3):383-6
references.pmid: 7906254
references.citation: Int J Cancer. 1994 Feb 15;56(4):522-8
references.pmid: 7906679
references.citation: J Clin Invest. 1994 Feb;93(2):516-20
references.pmid: 7906694
references.citation: Mol Cell Biol. 1993 Apr;13(4):2247-57
references.pmid: 8096058
references.citation: Oncogene. 1993 Nov;8(11):2917-23
references.pmid: 8105438
references.citation: Mutat Res. 1995 Dec;333(1-2):203-8
references.pmid: 8538628
references.citation: Gynakol Geburtshilfliche Rundsch. 1995;35 Suppl 1:157-60
references.pmid: 8672918
references.citation: Eur J Cancer. 1996 Jan;32A(1):134-40
references.pmid: 8695221
references.citation: In Vivo. 1997 Jan-Feb;11(1):51-4
references.pmid: 9067773
references.citation: Tumour Biol. 1997;18(3):188-96
references.pmid: 9143415
references.citation: J Obstet Gynaecol Res. 1997 Apr;23(2):213-7
references.pmid: 9158311
references.citation: Anticancer Res. 1997 Jul-Aug;17(4B):3075-7
references.pmid: 9329605
references.citation: Med Hypotheses. 1998 May;50(5):359-62
references.pmid: 9681912
references.citation: Clin Cancer Res. 1995 Jun;1(6):659-64
references.pmid: 9816029
references.citation: J Immunol Methods. 1998 Oct 1;219(1-2):23-43
references.pmid: 9831386