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Prognostic value of delta‑like protein 3 combined with thyroid transcription factor‑1 in small‑cell lung cancer

  • Authors:
    • Li‑Xu Yan
    • Yan‑Hui Liu
    • Zhi Li
    • Dong‑Lan Luo
    • Yu‑Fa Li
    • Jing‑Hai Yan
    • Jia‑Tao Zhang
    • Chao Liu
    • Xun‑Hua Liu
    • Jiao He
  • View Affiliations / Copyright

    Affiliations: Department of Pathology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, P.R. China, Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, P.R. China
    Copyright: © Yan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2254-2261
    |
    Published online on: June 27, 2019
       https://doi.org/10.3892/ol.2019.10538
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Abstract

Rovalpituzumab tesirine is a promising delta‑like protein 3 (DLL3)‑targeted antibody‑drug conjugate for the treatment of small‑cell lung cancer (SCLC). Thyroid transcription factor‑1 (TTF‑1) and DLL3 protein are associated with SCLC, and may be used to identify patients, who respond to the DLL3‑targeted therapy. However, little is known about the expression pattern of the DLL3 protein, and the prognostic value of DLL3 and TTF‑1 for SCLC. A total of 335 patients with SCLC were identified, including 11 patients with paired biopsy of primary site and lobectomy specimens, and 37 patients with paired specimens of primary and metastatic site. The DLL3 expression levels of individuals were evaluated using the anti‑DLL3 antibody. No differences in DLL3 expression levels were observed in paired biopsy and lobectomy specimens (P=0.774), and paired primary and metastatic sites (P=0.472). SCLC cases with high DLL3 expression levels were more frequent in male patients (P=0.041), smokers (P=0.023) and patients with positive TTF‑1 expression (P=0.006) compared with DLL3‑low SCLC. DLL3‑high SCLC exhibited worse overall survival compared with DLL3‑low SCLC (log‑rank test, P=0.007). Patients with TTF‑1+ SCLC experienced a significantly worse overall survival compared with patients with TTF‑1‑ SCLC (P<0.001). DLL3‑low/TTF‑1‑ was defined as a distinct molecular subgroup of SCLC with optimal prognosis (P<0.001). DLL3‑low/TTF‑1‑ was an independent prognostic marker for SCLC (P=0.001). In conclusion, the present study, to the best of our knowledge, provided novel evidence for SCLC intratumoral and intertumoral homogeneity with the identification of DLL3 protein levels. Therefore, it is reliable to use biopsy specimens to evaluate DLL3 expression levels for identification of patients who may benefit from DLL3‑targeted therapy. In addition, DLL3 and TTF‑1 are two protein markers with potential clinical value in risk stratification for patients with SCLC.
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1 

Baize N, Monnet I, Greillier L, Quere G, Kerjouan M, Janicot H, Vergnenegre A, Auliac JB and Chouaid C: Second-line treatments of small-cell lung cancers. Expert Rev Anticancer Ther. 17:1033–1043. 2017. View Article : Google Scholar : PubMed/NCBI

2 

Asamura H, Kameya T, Matsuno Y, Noguchi M, Tada H, Ishikawa Y, Yokose T, Jiang SX, Inoue T, Nakagawa K, et al: Neuroendocrine neoplasms of the lung: A prognostic spectrum. J Clin Oncol. 24:70–76. 2006. View Article : Google Scholar : PubMed/NCBI

3 

Metro G, Ricciuti B, Chiari R, Baretti M, Falcinelli L, Giannarelli D, Sidoni A, Mountzios G, Crinò L, Bellezza G, et al: Survival outcomes and incidence of brain recurrence in high-grade neuroendocrine carcinomas of the lung: Implications for clinical practice. Lung Cancer. 95:82–87. 2016. View Article : Google Scholar : PubMed/NCBI

4 

Travis WD: Advances in neuroendocrine lung tumors. Ann Oncol. 21 (Suppl 7):vii65–71. 2010. View Article : Google Scholar : PubMed/NCBI

5 

van Meerbeeck JP, Fennell DA and De Ruysscher DK: Small-cell lung cancer. Lancet. 378:1741–1755. 2011. View Article : Google Scholar : PubMed/NCBI

6 

Rudin CM, Pietanza MC, Bauer TM, Ready N, Morgensztern D, Glisson BS, Byers LA, Johnson ML, Burris HA III, Robert F, et al: Rovalpituzumab tesirine, a DLL3-targeted antibody-drug conjugate, in recurrent small-cell lung cancer: A first-in-human, first-in-class, open-label, phase 1 study. Lancet Oncol. 18:42–51. 2017. View Article : Google Scholar : PubMed/NCBI

7 

Saunders LR, Bankovich AJ, Anderson WC, Aujay MA, Bheddah S, Black K, Desai R, Escarpe PA, Hampl J, Laysang A, et al: A DLL3-targeted antibody-drug conjugate eradicates high-grade pulmonary neuroendocrine tumor-initiating cells in vivo. Sci Transl Med. 7:302ra1362015. View Article : Google Scholar : PubMed/NCBI

8 

Gazdar AF, Bunn PA and Minna JD: Small-cell lung cancer: What we know, what we need to know and the path forward. Nat Rev Cancer. 17:725–737. 2017. View Article : Google Scholar : PubMed/NCBI

9 

Bauer TM, Spigel D, Ready N, Morgensztern D, Glisson BS, Byers LA, Burris H, Robert F, Strickland DK, Pietanza MC, Govindan R Dylla SJ, Peng S and Rudin C: ORAL02.01: Safety and efficacy of single-agent rovalpituzumab tesirine, a DLL3-targeted ADC, in recurrent or refractory SCLC: Topic: Medical oncology. J Thorac Oncol. 11:S252–S253. 2016. View Article : Google Scholar

10 

Tanaka K, Isse K, Fujihira T, Takenoyama M, Saunders L, Bheddah S, Nakanishi Y and Okamoto I: Prevalence of delta-like protein 3 expression in patients with small cell lung cancer. Lung Cancer. 115:116–120. 2018. View Article : Google Scholar : PubMed/NCBI

11 

Sharma SK, Pourat J, Abdel-Atti D, Carlin SD, Piersigilli A, Bankovich AJ, Gardner EE, Hamdy O, Isse K, Bheddah S, et al: Noninvasive interrogation of DLL3 expression in metastatic small cell lung cancer. Cancer Res. 77:3931–3941. 2017. View Article : Google Scholar : PubMed/NCBI

12 

Sakaeda M, Sato H, Ishii J, Miyata C, Kamma H, Shishido-Hara Y, Shimoyamada H, Fujiwara M, Endo T, Tanaka R, et al: Neural lineage-specific homeoprotein BRN2 is directly involved in TTF1 expression in small-cell lung cancer. Lab Invest. 93:408–421. 2013. View Article : Google Scholar : PubMed/NCBI

13 

Misch D, Blum T, Boch C, Weiss T, Crolow C, Griff S, Mairinger T, Bauer TT and Kollmeier J: Value of thyroid transcription factor (TTF)-1 for diagnosis and prognosis of patients with locally advanced or metastatic small cell lung cancer. Diagn Pathol. 10:212015. View Article : Google Scholar : PubMed/NCBI

14 

Kitamura H, Yazawa T, Sato H, Okudela K and Shimoyamada H: Small cell lung cancer: Significance of RB alterations and TTF-1 expression in its carcinogenesis, phenotype, and biology. Endocr Pathol. 20:101–107. 2009. View Article : Google Scholar : PubMed/NCBI

15 

Mukhopadhyay S and Katzenstein AL: Subclassification of non-small cell lung carcinomas lacking morphologic differentiation on biopsy specimens: Utility of an immunohistochemical panel containing TTF-1, napsin a, p63, and CK5/6. Am J Surg Pathol. 35:15–25. 2011. View Article : Google Scholar : PubMed/NCBI

16 

Cardnell RJ, Li L, Sen T, Bara R, Tong P, Fujimoto J, Ireland AS, Guthrie MR, Bheddah S, Banerjee U, et al: Protein expression of TTF1 and cMYC define distinct molecular subgroups of small cell lung cancer with unique vulnerabilities to aurora kinase inhibition, DLL3 targeting, and other targeted therapies. Oncotarget. 8:73419–73432. 2017. View Article : Google Scholar : PubMed/NCBI

17 

Brambilla E, Beasley MB, Austin JHM, Capelozzi VL, Chirieac LR, Devesa SS, Frank GA, Gazdar A, Ishikawa Y, Jen J, et al: Small cell carcinoma. WHO classification of tumors of the lung, pleura, thymus and heart. Travis WD, Brambilla E, Burke AP, Marx A and Nicholson AG: IARC; Lyon: pp. 62–68. 2015

18 

Detterbeck FC, Boffa DJ, Kim AW and Tanoue LT: The eighth edition lung cancer stage classification. Chest. 151:193–203. 2017. View Article : Google Scholar : PubMed/NCBI

19 

Welti J, Rodrigues DN, Sharp A, Sun S, Lorente D, Riisnaes R, Figueiredo I, Zafeiriou Z, Rescigno P, de Bono JS and Plymate SR: Analytical validation and clinical qualification of a new immunohistochemical assay for androgen receptor splice variant-7 protein expression in metastatic castration-resistant prostate cancer. Eur Urol. 70:599–608. 2016. View Article : Google Scholar : PubMed/NCBI

20 

Sabari JK, Lok BH, Laird JH, Poirier JT and Rudin CM: Unravelling the biology of SCLC: Implications for therapy. Nat Rev Clin Oncol. 14:549–561. 2017. View Article : Google Scholar : PubMed/NCBI

21 

Chapman G, Sparrow DB, Kremmer E and Dunwoodie SL: Notch inhibition by the ligand DELTA-LIKE 3 defines the mechanism of abnormal vertebral segmentation in spondylocostal dysostosis. Hum Mol Genet. 20:905–916. 2011. View Article : Google Scholar : PubMed/NCBI

22 

Hiroshima K, Iyoda A, Shida T, Shibuya K, Iizasa T, Kishi H, Tanizawa T, Fujisawa T and Nakatani Y: Distinction of pulmonary large cell neuroendocrine carcinoma from small cell lung carcinoma: A morphological, immunohistochemical, and molecular analysis. Mod Pathol. 19:1358–1368. 2006. View Article : Google Scholar : PubMed/NCBI

23 

Myong NH: Thyroid transcription factor-1 (TTF-1) expression in human lung carcinomas: Its prognostic implication and relationship with expressions of p53 and Ki-67 proteins. J Korean Med Sci. 18:494–500. 2003. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Yan LX, Liu YH, Li Z, Luo DL, Li YF, Yan JH, Zhang JT, Liu C, Liu XH, He J, He J, et al: Prognostic value of delta‑like protein 3 combined with thyroid transcription factor‑1 in small‑cell lung cancer. Oncol Lett 18: 2254-2261, 2019.
APA
Yan, L., Liu, Y., Li, Z., Luo, D., Li, Y., Yan, J. ... He, J. (2019). Prognostic value of delta‑like protein 3 combined with thyroid transcription factor‑1 in small‑cell lung cancer. Oncology Letters, 18, 2254-2261. https://doi.org/10.3892/ol.2019.10538
MLA
Yan, L., Liu, Y., Li, Z., Luo, D., Li, Y., Yan, J., Zhang, J., Liu, C., Liu, X., He, J."Prognostic value of delta‑like protein 3 combined with thyroid transcription factor‑1 in small‑cell lung cancer". Oncology Letters 18.3 (2019): 2254-2261.
Chicago
Yan, L., Liu, Y., Li, Z., Luo, D., Li, Y., Yan, J., Zhang, J., Liu, C., Liu, X., He, J."Prognostic value of delta‑like protein 3 combined with thyroid transcription factor‑1 in small‑cell lung cancer". Oncology Letters 18, no. 3 (2019): 2254-2261. https://doi.org/10.3892/ol.2019.10538
Copy and paste a formatted citation
x
Spandidos Publications style
Yan LX, Liu YH, Li Z, Luo DL, Li YF, Yan JH, Zhang JT, Liu C, Liu XH, He J, He J, et al: Prognostic value of delta‑like protein 3 combined with thyroid transcription factor‑1 in small‑cell lung cancer. Oncol Lett 18: 2254-2261, 2019.
APA
Yan, L., Liu, Y., Li, Z., Luo, D., Li, Y., Yan, J. ... He, J. (2019). Prognostic value of delta‑like protein 3 combined with thyroid transcription factor‑1 in small‑cell lung cancer. Oncology Letters, 18, 2254-2261. https://doi.org/10.3892/ol.2019.10538
MLA
Yan, L., Liu, Y., Li, Z., Luo, D., Li, Y., Yan, J., Zhang, J., Liu, C., Liu, X., He, J."Prognostic value of delta‑like protein 3 combined with thyroid transcription factor‑1 in small‑cell lung cancer". Oncology Letters 18.3 (2019): 2254-2261.
Chicago
Yan, L., Liu, Y., Li, Z., Luo, D., Li, Y., Yan, J., Zhang, J., Liu, C., Liu, X., He, J."Prognostic value of delta‑like protein 3 combined with thyroid transcription factor‑1 in small‑cell lung cancer". Oncology Letters 18, no. 3 (2019): 2254-2261. https://doi.org/10.3892/ol.2019.10538
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