Human epididymis protein 4 may not be a reliable screening biomarker for detecting lung carcinoma patients

Celik,Betul; Bulut,Tangul

doi:10.3892/br.2017.971

Human epididymis protein 4 may not be a reliable screening biomarker for detecting lung carcinoma patients

Authors:
- Betul Celik
- Tangul Bulut
View Affiliations

Affiliations: Department of Pathology, University of Health Sciences, Antalya Training and Research Hospital, Antalya 07050, Turkey
Published online on: August 25, 2017 https://doi.org/10.3892/br.2017.971
Pages: 297-300

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Human epididymis protein 4 (HE4) acts as a protease inhibitor. It has been detected in the serum of patients with lung cancer patients and its utility for lung cancer screening was found in different studies. Nevertheless, little is known regarding the expression of HE4 in lung carcinoma subtypes. The aim of the present study was to investigate whether HE4 expression is a reliable marker for detecting any lung carcinoma subtypes, including small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC) and adenocarcinoma (AC). In total, 141 lung carcinoma patients were enrolled in the study. Biopsy samples were obtained from bronchoscopic biopsy. The tumors were classified as SCLC (group 1, 54 cases) or NSCLC (group 2, 87 cases) based on histology and immunohistochemistry. The latter was sub-grouped as adenocarcinoma (group 2a, AC) and squamous cell carcinoma (group 2b, SCC). The immunohistochemical expression of HE4 was compared between the groups. The study revealed that the majority of the SCLC and SCC cases were devoid of HE4 (90.1 and 89.65%, respectively). Approximately 10% of cases had HE4 immune expression and the staining was focal and moderate throughout the tumor tissue. On the other hand, 78.8% of AC expressed HE4 and the staining was diffuse and strong. The overall HE4 expression in the lung cancer patients was 33.7%. In conclusion, the results of the present study have shown that HE4 is expressed in adenocarcinoma of the lung but it is not frequent in SCC and SCLC. The value of HE4 as a screening biomarker for lung cancer is limited but its presence exclusively in adenocarcinoma may provide new insight for targeted therapy.

View Figures

View References

1	Kirchhoff C, Habben I, Ivell R and Krull N: A major human epididymis-specific cDNA encodes a protein with sequence homology to extracellular proteinase inhibitors. Biol Reprod. 45:350–357. 1991. View Article : Google Scholar : PubMed/NCBI
2	Ma Q, Wang Q and Zhong D: Advances of human epididymis protein 4 in lung cancer. Zhongguo Fei Ai Za Zhi. 18:184–186. 2015.(In Chinese). PubMed/NCBI
3	Hua L, Liu Y, Zhen S, Wan D, Cao J and Gao X: Expression and biochemical characterization of recombinant human epididymis protein 4. Protein Expr Purif. 102:52–62. 2014. View Article : Google Scholar : PubMed/NCBI
4	Lu R, Sun X, Xiao R, Zhou L, Gao X and Guo L: Human epididymis protein 4 (HE4) plays a key role in ovarian cancer cell adhesion and motility. Biochem Biophys Res Commun. 419:274–280. 2012. View Article : Google Scholar : PubMed/NCBI
5	Bingle L, Cross SS, High AS, Wallace WA, Rassl D, Yuan G, Hellstrom I, Campos MA and Bingle CD: WFDC2 (HE4): A potential role in the innate immunity of the oral cavity and respiratory tract and the development of adenocarcinomas of the lung. Respir Res. 7:612006. View Article : Google Scholar : PubMed/NCBI
6	Zeng Q, Liu M, Zhou N, Liu L and Song X: Serum human epididymis protein 4 (HE4) may be a better tumor marker in early lung cancer. Clin Chim Acta. 455:102–106. 2016. View Article : Google Scholar : PubMed/NCBI
7	Wang X, Fan Y, Wang J, Wang H and Liu W: Evaluating the expression and diagnostic value of human epididymis protein 4 (HE4) in small cell lung cancer. Tumour Biol. 35:6847–6853. 2014. View Article : Google Scholar : PubMed/NCBI
8	Liu W, Yang J, Chi PD, Zheng X, Dai SQ, Chen H, Xu BL and Liu WL: Evaluating the clinical significance of serum HE4 levels in lung cancer and pulmonary tuberculosis. Int J Tuberc Lung Dis. 17:1346–1353. 2013. View Article : Google Scholar : PubMed/NCBI
9	Yamashita S, Tokuishi K, Moroga T, Yamamoto S, Ohbo K, Miyahara S, Yoshida Y, Yanagisawa J, Hamatake D, Hiratsuka M, et al: Serum level of HE4 is closely associated with pulmonary adenocarcinoma progression. Tumour Biol. 33:2365–2370. 2012. View Article : Google Scholar : PubMed/NCBI
10	Wojcik E, Tarapacz J, Rychlik U, Stasik Z, Sas-Korczynska B, Skotnicki P and Kulpa JK: Human epididymis protein 4 (HE4) in patients with small-cell lung cancer. Clin Lab. 62:1625–1632. 2016. View Article : Google Scholar : PubMed/NCBI
11	Lan WG, Hao YZ, Xu DH, Wang P, Zhou YL and Ma LB: Serum human epididymis protein 4 is associated with the treatment response of concurrent chemoradiotherapy and prognosis in patients with locally advanced non-small cell lung cancer. Clin Transl Oncol. 18:375–380. 2016. View Article : Google Scholar : PubMed/NCBI
12	Yamashita S, Tokuishi K, Hashimoto T, Moroga T, Kamei M, Ono K, Miyawaki M, Takeno S, Chujo M, Yamamoto S, et al: Prognostic significance of HE4 expression in pulmonary adenocarcinoma. Tumour Biol. 32:265–271. 2011. View Article : Google Scholar : PubMed/NCBI
13	Bulut T, Celik B, Yalcin AD and Keser S: Tissue expression of HE4 a and its correlation with CA125 and P53 in high grade serous ovarian carcinoma. Eur J Gynaecol Oncol. doi: 10.12892/ejgo3992.2017 (Epub ahead of print). PubMed/NCBI
14	Yang Z, Zhang Z, Qin B, et al: Human epididymis protein 4: A novel biomarker for lupus nephritis and chronic kidney disease in systemic lupus erythematosus. J Clin Lab Anal. 897–904. 2016.doi: 10.1002/jcla.21954. View Article : Google Scholar : PubMed/NCBI
15	Yoon HI, Kwon OR, Kang KN, Shin YS, Shin HS, Yeon EH, Kwon KY, Hwang I, Jeon YK, Kim Y, et al: Diagnostic value of combining tumor and inflammatory markers in lung cancer. J Cancer Prev. 21:187–193. 2016. View Article : Google Scholar : PubMed/NCBI
16	Nagy B Jr, Bhattoa HP, Steiber Z, Csobán M, Szilasi M, Méhes G, Müller M, Lázár J, Kappelmayer J and Antal-Szalmás P: Serum human epididymis protein 4 (HE4) as a tumor marker in men with lung cancer. Clin Chem Lab Med. 52:1639–1648. 2014. View Article : Google Scholar : PubMed/NCBI
17	Iwahori K, Suzuki H, Kishi Y, Fujii Y, Uehara R, Okamoto N, Kobayashi M, Hirashima T, Kawase I and Naka T: Serum HE4 as a diagnostic and prognostic marker for lung cancer. Tumour Biol. 33:1141–1149. 2012. View Article : Google Scholar : PubMed/NCBI
18	Tang QF, Zhou ZW, Ji HB, Pan WH and Sun MZ: Value of serum marker HE4 in pulmonary carcinoma diagnosis. Int J Clin Exp Med. 8:19014–19021. 2015.PubMed/NCBI
19	Huang W, Wu S, Lin Z, Chen P and Wu G: Evaluation of HE4 in the diagnosis and follow up of non-small cell lung cancers. Clin Lab. 63:461–467. 2017. View Article : Google Scholar : PubMed/NCBI
20	Lou E, Johnson M, Sima C, Gonzalez-Espinoza R, Fleisher M, Kris MG and Azzoli CG: Serum biomarkers for assessing histology and outcomes in patients with metastatic lung cancer. Cancer Biomark. 14:207–214. 2014. View Article : Google Scholar : PubMed/NCBI
21	Drapkin R, von Horsten HH, Lin Y, Mok SC, Crum CP, Welch WR and Hecht JL: Human epididymis protein 4 (HE4) is a secreted glycoprotein that is overexpressed by serous and endometrioid ovarian carcinomas. Cancer Res. 65:2162–2169. 2005. View Article : Google Scholar : PubMed/NCBI
22	Mangum MD, Greco FA, Hainsworth JD, Hande KR and Johnson DH: Combined small-cell and non-small-cell lung cancer. J Clin Oncol. 7:607–612. 1989. View Article : Google Scholar : PubMed/NCBI
23	Wallace AS, Arya M, Frazier SR, Westgate S, Wang Z and Doll D: Combined small-cell lung carcinoma: An institutional experience. Thorac Cancer. 5:57–62. 2014. View Article : Google Scholar : PubMed/NCBI