Serum sRANKL and sRANKL/OPG ratio: Novel biomarkers in non‑small cell lung cancer

Lu,Chengjun; Sun,Chao; Jin,Hai

doi:10.3892/ol.2016.4166

Serum sRANKL and sRANKL/OPG ratio: Novel biomarkers in non‑small cell lung cancer

Authors:
- Chengjun Lu
- Chao Sun
- Hai Jin
View Affiliations

Affiliations: Department of Cardiothoracic Surgery, Changhai Hospital of Shanghai Affiliated to The Second Military Medical University, Shanghai 200433, P.R. China, Hematology Department, Wuxi People's Hospital, Affiliated to Nanjing Medical University, Nanchang, Wuxi 214023, P.R. China
Published online on: January 29, 2016 https://doi.org/10.3892/ol.2016.4166
Pages: 2261-2265

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

Osteoprotegerin (OPG) and soluble receptor activator of nuclear factor‑κB ligand (sRANKL) are bone‑regulating molecules. The two molecules have each been indicated to be involved in carcinogenesis. However, the diagnostic significance in non‑small cell lung cancer (NSCLC) remains to be investigated. Thus, the objective of the present study was to investigate the serum levels of OPG and sRANKL in NSCLC patients, and to analyze their clinical significance. Serum OPG and sRANKL levels were determined in 50 patients with NSCLC, matched with 25 patients with benign lung nodule and 25 healthy controls by enzyme‑linked immunosorbent assay. The level of serum sRANKL and the sRANKL/OPG ratio were significant elevated in the patients with NSCLC compared with the benign lung nodule patients and the healthy controls. Receiver operating characteristic curves were used to evaluate the performance of sRANKL and sRANKL/OPG. When the cut‑off values for the sRANKL level and the sRANKL/OPG ratio were set at 4.20 pmol/l and 0.60, respectively, the sensitivity, specificity and accuracy of sRANKL were 74.0, 84.0 and 77.3%, respectively. Moreover, the sensitivity, specificity and accuracy of the sRANKL/OPG ratio were 84.0, 88.0 and 85.3%, respectively. On the other hand, when the cut‑off values of the serum sRANKL level and the sRANKL/OPG ratio were set at 5.24 pmol/l and 0.63, respectively, the sensitivity, specificity and accuracy of sRANKL were 60.0, 84.0 and 68.0%, respectively. The sensitivity, specificity and accuracy of the ratio were 78.0, 64.0 and 73.3%, respectively. The OPG/RANKL system may be involved in the pathogenesis of NSCLC. More importantly, the serum sRANKL level and the sRANKL/OPG ratio may have the potential to be novel biomarkers for the diagnosis of NSCLC.

View Figures

View References

1	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI
2	Wang Y, Gu J, Roth JA, Hildebrandt MA, Lippman SM, Ye Y, Minna JD and Wu X: Pathway-based serum microRNA profiling and survival in patients with advanced stage non-small cell lung cancer. Cancer Res. 73:4801–4809. 2013. View Article : Google Scholar : PubMed/NCBI
3	Ourari-Dhahri B, Ben Slima H, Ben Amar J, El Gharbi L, Ali M, Azzabi Baccar S, Aouina H and Bouacha H: Management of non small cell lung cancer. Tunis Med. 90:847–851. 2012.(In French). PubMed/NCBI
4	Kuner R, Muley T, Meister M, Ruschhaupt M, Buness A, Xu EC, Schnabel P, Warth A, Poustka A, Sültmann H and Hoffmann H: Global gene expression analysis reveals specific patterns of cell junctions in non-small cell lung cancer subtypes. Lung Cancer. 63:32–38. 2009. View Article : Google Scholar : PubMed/NCBI
5	Esteban E, Casillas M and Cassinello A: Pemetrexed in first-line treatment of non-small cell lung cancer. Cancer Treat Rev. 35:364–373. 2009. View Article : Google Scholar : PubMed/NCBI
6	Peng X, Guo W, Ren T, Lou Z, Lu X, Zhang S, Lu Q and Sun Y: Differential expression of the RANKL/RANK/OPG system is associated with bone metastasis in human non-small cell lung cancer. PLoS One. 8:e583612013. View Article : Google Scholar : PubMed/NCBI
7	Kong YY, Feige U, Sarosi I, Bolon B, Tafuri A, Morony S, Capparelli C, Li J, Elliott R, McCabe S, et al: Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand. Nature. 402:304–309. 1999. View Article : Google Scholar : PubMed/NCBI
8	Harada S and Takahashi N: Control of bone resorption by RANKL-RANK system. Clin Calcium. 21:1121–1130. 2011.(In Japanese). PubMed/NCBI
9	Hanada R, Hanada T, Sigl V, Schramek D and Penninger JM: RANKL/RANK-beyond bones. J Mol Med (Berl). 89:647–656. 2011. View Article : Google Scholar : PubMed/NCBI
10	Peters S and Meylan E: Targeting receptor activator of nuclear factor-kappa B as a new therapy for bone metastasis in non-small cell lung cancer. Curr Opin Oncol. 25:137–144. 2013. View Article : Google Scholar : PubMed/NCBI
11	Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger KR, Yatabe Y, Beer DG, Powell CA, Riely GJ, Van Schil PE, et al: International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol. 6:244–285. 2011. View Article : Google Scholar : PubMed/NCBI
12	Fluss R, Faraggi D and Reiser B: Estimation of the Youden Index and its associated cutoff point. Biom J. 47:458–472. 2005. View Article : Google Scholar : PubMed/NCBI
13	Diamandis EP, Goodglick L, Planque C and Thornquist MD: Pentraxin-3 is a novel biomarker of lung carcinoma. Clin Cancer Res. 17:2395–2399. 2011. View Article : Google Scholar : PubMed/NCBI
14	Wiedemann GJ: Biomarker screening for early detection of cance. Dtsch Med Wochenschr. 138:43–45. 2013.(In German). PubMed/NCBI
15	Ferrigno D, Buccheri G and Giordano C: Neuron-specific enolase is an effective tumour marker in non-small cell lung cancer (NSCLC). Lung Cancer. 41:311–320. 2003. View Article : Google Scholar : PubMed/NCBI
16	Strathmann FG, Schulte S, Goerl K and Petron DJ: Blood-based biomarkers for traumatic brain injury: Evaluation of research approaches, available methods and potential utility from the clinician and clinical laboratory perspectives. Clin Biochem. 47:876–888. 2014. View Article : Google Scholar : PubMed/NCBI
17	Ibrahim T, Sacanna E, Gaudio M, Mercatali L, Scarpi E, Zoli W, Serra P, Ricci R, Serra L, Kang Y and Amadori D: Role of RANK, RANKL, OPG and CXCR4 tissue markers in predicting bone metastases in breast cancer patients. Clin Breast Cancer. 11:369–375. 2011. View Article : Google Scholar : PubMed/NCBI
18	Dougall WC and Chaisson M: The RANK/RANKL/OPG triad in cancer-induced bone diseases. Cancer Metastasis Rev. 25:541–549. 2006. View Article : Google Scholar : PubMed/NCBI
19	Owen S, Ye L, Sanders AJ, Mason MD and Jiang WG: Expression profile of receptor activator of nuclear-κB (RANK), RANK ligand (RANKL) and osteoprotegerin (OPG) in breast cancer. Anticancer Res. 33:199–206. 2013.PubMed/NCBI
20	Karapanagiotou EM, Terpos E, Dilana KD, Alamara C, Gkiozos I, Polyzos A and Syrigos KN: Serum bone turnover markers may be involved in the metastatic potential of lung cancer patients. Med Oncol. 27:332–338. 2010. View Article : Google Scholar : PubMed/NCBI
21	Silva I and Branco JC: Rank/Rankl/opg: Literature review. Acta Reumatol Port. 36:209–218. 2011.PubMed/NCBI
22	Shu J, Li CG, Liu YC, Yan XC, Xu X, Huang XE, Cao J, Li Y, Lu YY, Wu XY, et al: Comparison of serum tumor associated material (TAM) with conventional biomarkers in cancer patients. Asian Pac J Cancer Prev. 13:2399–2403. 2012. View Article : Google Scholar : PubMed/NCBI
23	Prisadov GT, Uchikov AP, Welker K, Wallimann H, Murdzhev KA and Uzunova VN: Size of tumour as a risk factor for malignancy in patients with peripheral pulmonary nodules. Folia Med (Plovdiv). 54:17–21. 2012.PubMed/NCBI