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Journal of Cancer Research and Clinical Oncology

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20.09.2019 | Original Article – Cancer Research

Expression and clinical significance of PD-L1 and c-Myc in non-small cell lung cancer

verfasst von: Cuiling Zhou, Gang Che, Xiaobin Zheng, Junlan Qiu, Zhinan Xie, Yunyan Cong, Xiaofeng Pei, Hongyu Zhang, Huanhuan Sun, Haiqing Ma

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 11/2019

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Abstract

Background

It is known that there are insufficient prognostic factors for non-small cell lung cancer (NSCLC). It was reported that PD-L1 was a prognostic factor for NSCLC,and c-Myc regulated the expression of PD-L1. Herein, we investigated c-Myc and PD-L1 expression and their association with overall survival (OS) in NSCLC.

Methods

Formalin-fixed paraffin-embedded specimens were obtained from 128 patients with surgically resected primary NSCLC. Immunohistochemistry was used to assess the expression of PD-L1 and c-Myc in this study. Pearson’s Chi squared test or Fisher’s exact test was used to analyze the correlation of the expression of PD-L1 and c-Myc with clinicopathologic features. The relationship between OS and the expression of PD-L1 and c-Myc was evaluated by the Kaplan–Meier method and Cox proportional hazards model, respectively.

Results

Positive expression of PD-L1 was detected in 59 patients (46.1%). Patients with negative expression of PD-L1 had remarkably longer OS than those with positive expression of PD-L1. The positive expression rate of c-Myc in NSCLC accounted for 58.6% (75/128) and its expression was significantly more frequent in males (p = 0.002) and patients with lymph node metastasis (p = 0.029). PD-L1 expression was positively correlated with c-Myc expression (r = 0.459, p < 0.001). The PD-L1 and c-Myc double-positive group had a worse prognosis than other subgroups (p < 0.05), and the PD-L1 and c-Myc double-negative group had a better OS than other subgroups (p < 0.05).

Conclusion

Conjoint analysis of the expression of PD-L1 and c-Myc was a better prognostic approach for NSCLC patients.

Akbay EA, Koyama S, Carretero J, Altabef A, Tchaicha JH, Christensen CL et al (2013) Activation of the PD-1 pathway contributes to immune escape in EGFR-driven lung tumors. Cancer Discov 3(12):1355–1363. https://doi.org/10.1158/2159-8290.Cd-13-0310 CrossRefPubMed

Atsaves V, Tsesmetzis N, Chioureas D, Kis L, Leventaki V, Drakos E et al (2017) PD-L1 is commonly expressed and transcriptionally regulated by STAT3 and MYC in ALK-negative anaplastic large-cell lymphoma. Leukemia 31(7):1633–1637. https://doi.org/10.1038/leu.2017.103 CrossRefPubMed

Casey SC, Tong L, Li Y, Do R, Walz S, Fitzgerald KN et al (2016) MYC regulates the antitumor immune response through CD47 and PD-L1. Science 352(6282):227–231. https://doi.org/10.1126/science.aac9935 CrossRefPubMedPubMedCentral

Chae YK, Pan A, Davis AA, Raparia K, Mohindra NA, Matsangou M et al (2016) Biomarkers for PD-1/PD-L1 blockade therapy in non-small-cell lung cancer: is PD-L1 expression a good marker for patient selection? Clin Lung Cancer. https://doi.org/10.1016/j.cllc.2016.03.011 CrossRefPubMed

Choueiri TK, Fay AP, Gray KP, Callea M, Ho TH, Albiges L et al (2014) PD-L1 expression in nonclear-cell renal cell carcinoma. Ann Oncol 25(11):2178–2184. https://doi.org/10.1093/annonc/mdu445 CrossRefPubMedPubMedCentral

Cooper WA, Tran T, Vilain RE, Madore J, Selinger CI, Kohonen-Corish M et al (2015) PD-L1 expression is a favorable prognostic factor in early stage non-small cell carcinoma. Lung Cancer 89(2):181–188. https://doi.org/10.1016/j.lungcan.2015.05.007 CrossRefPubMed

Dang CV (1999) c-Myc target genes involved in cell growth, apoptosis, and metabolism. Mol Cell Biol 19(1):1–11CrossRefPubMedPubMedCentral

Dang CV, O’Donnell KA, Zeller KI, Nguyen T, Osthus RC, Li F (2006) The c-Myc target gene network. Semin Cancer Biol 16(4):253–264. https://doi.org/10.1016/j.semcancer.2006.07.014 CrossRefPubMed

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M et al (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136(5):E359–E386. https://doi.org/10.1002/ijc.29210 CrossRefPubMed

Guo R, Li Y, Wang Z, Bai H, Duan J, Wang S et al (2019) HIF-1alpha and NF-kappaB play important roles in regulating PD-L1 expression by EGFR mutants in non-small cell lung cancer cells. Cancer Sci. https://doi.org/10.1111/cas.13989 CrossRefPubMedPubMedCentral

Henriksson M, Luscher B (1996) Proteins of the Myc network: essential regulators of cell growth and differentiation. Adv Cancer Res 68:109–182CrossRefPubMed

Hino R, Kabashima K, Kato Y, Yagi H, Nakamura M, Honjo T et al (2010) Tumor cell expression of programmed cell death-1 ligand 1 is a prognostic factor for malignant melanoma. Cancer 116(7):1757–1766. https://doi.org/10.1002/cncr.24899 CrossRefPubMed

Ilie M, Hofman V, Dietel M, Soria JC, Hofman P (2016) Assessment of the PD-L1 status by immunohistochemistry: challenges and perspectives for therapeutic strategies in lung cancer patients. Virchows Arch 468(5):511–525. https://doi.org/10.1007/s00428-016-1910-4 CrossRefPubMed

Iwakawa R, Kohno T, Kato M, Shiraishi K, Tsuta K, Noguchi M et al (2011) MYC amplification as a prognostic marker of early-stage lung adenocarcinoma identified by whole genome copy number analysis. Clin Cancer Res 17(6):1481–1489. https://doi.org/10.1158/1078-0432.CCR-10-2484 CrossRefPubMed

Kim YH, Girard L, Giacomini CP, Wang P, Hernandez-Boussard T, Tibshirani R et al (2006) Combined microarray analysis of small cell lung cancer reveals altered apoptotic balance and distinct expression signatures of MYC family gene amplification. Oncogene 25(1):130–138. https://doi.org/10.1038/sj.onc.1208997 CrossRefPubMed

Kim EY, Kim A, Kim SK, Chang YS (2017) MYC expression correlates with PD-L1 expression in non-small cell lung cancer. Lung Cancer 110:63–67. https://doi.org/10.1016/j.lungcan.2017.06.006 CrossRefPubMed

Konishi J, Yamazaki K, Azuma M, Kinoshita I, Dosaka-Akita H, Nishimura M (2004) B7-H1 expression on non-small cell lung cancer cells and its relationship with tumor-infiltrating lymphocytes and their PD-1 expression. Clinical Cancer Res 10(15):5094–5100. https://doi.org/10.1158/1078-0432.Ccr-04-0428 CrossRef

Lin CY, Loven J, Rahl PB, Paranal RM, Burge CB, Bradner JE et al (2012) Transcriptional amplification in tumor cells with elevated c-Myc. Cell 151(1):56–67. https://doi.org/10.1016/j.cell.2012.08.026 CrossRefPubMedPubMedCentral

Melaiu O, Mina M, Chierici M, Boldrini R, Jurman G, Romania P et al (2017) PD-L1 is a therapeutic target of the bromodomain inhibitor JQ1 and combined with HLA class I, a promising prognostic biomarker in neuroblastoma. Clin Cancer Res 23(15):4462–4472. https://doi.org/10.1158/1078-0432.Ccr-16-2601 CrossRefPubMed

Merelli B, Massi D, Cattaneo L, Mandala M (2014) Targeting the PD1/PD-L1 axis in melanoma: biological rationale, clinical challenges and opportunities. Crit Rev Oncol Hematol 89(1):140–165. https://doi.org/10.1016/j.critrevonc.2013.08.002 CrossRefPubMed

Mu CY, Huang JA, Chen Y, Chen C, Zhang XG (2011) High expression of PD-L1 in lung cancer may contribute to poor prognosis and tumor cells immune escape through suppressing tumor infiltrating dendritic cells maturation. Med Oncol 28(3):682–688. https://doi.org/10.1007/s12032-010-9515-2 CrossRefPubMed

Nakashima N, Liu D, Huang CL, Ueno M, Zhang X, Yokomise H (2012a) Wnt3 gene expression promotes tumor progression in non-small cell lung cancer. Lung Cancer 76(2):228–234CrossRefPubMed

Nakashima N, Liu D, Huang CL, Ueno M, Zhang X, Yokomise H (2012b) Wnt3 gene expression promotes tumor progression in non-small cell lung cancer. Lung Cancer 76(2):228–234. https://doi.org/10.1016/j.lungcan.2011.10.007 CrossRefPubMed

Nesbit CE, Tersak JM, Prochownik EV (1999) MYC oncogenes and human neoplastic disease. Oncogene 18(19):3004–3016. https://doi.org/10.1038/sj.onc.1202746 CrossRefPubMed

Nomi T, Sho M, Akahori T, Hamada K, Kubo A, Kanehiro H et al (2007) Clinical significance and therapeutic potential of the programmed death-1 ligand/programmed death-1 pathway in human pancreatic cancer. Clin Cancer Res 13(7):2151–2157. https://doi.org/10.1158/1078-0432.CCR-06-2746 CrossRefPubMed

Pan ZK, Ye F, Wu X, An HX, Wu JX (2015) Clinicopathological and prognostic significance of programmed cell death ligand1 (PD-L1) expression in patients with non-small cell lung cancer: a meta-analysis. J Thorac Dis 7(3):462–470. https://doi.org/10.3978/j.issn.2072-1439.2015.02.13 CrossRefPubMedPubMedCentral

Rapp UR, Korn C, Ceteci F, Karreman C, Luetkenhaus K, Serafin V et al (2009) MYC is a metastasis gene for non-small-cell lung cancer. PLoS One 4(6):e6029. https://doi.org/10.1371/journal.pone.0006029 CrossRefPubMedPubMedCentral

Sabo A, Kress TR, Pelizzola M, de Pretis S, Gorski MM, Tesi A et al (2014) Selective transcriptional regulation by Myc in cellular growth control and lymphomagenesis. Nature 511(7510):488–492. https://doi.org/10.1038/nature13537 CrossRefPubMedPubMedCentral

Schlosser I, Holzel M, Hoffmann R, Burtscher H, Kohlhuber F, Schuhmacher M et al (2005) Dissection of transcriptional programmes in response to serum and c-Myc in a human B-cell line. Oncogene 24(3):520–524. https://doi.org/10.1038/sj.onc.1208198 CrossRefPubMed

Schmidt LH, Kummel A, Gorlich D, Mohr M, Brockling S, Mikesch JH et al (2015) PD-1 and PD-L1 expression in NSCLC indicate a favorable prognosis in defined subgroups. PLoS One 10(8):e0136023. https://doi.org/10.1371/journal.pone.0136023 CrossRefPubMedPubMedCentral

Seo AN, Yang JM, Kim H, Jheon S, Kim K, Lee CT et al (2014) Clinicopathologic and prognostic significance of c-MYC copy number gain in lung adenocarcinomas. Br J Cancer 110(11):2688–2699. https://doi.org/10.1038/bjc.2014.218 CrossRefPubMedPubMedCentral

Siegel R, Naishadham D, Jemal A (2012) Cancer statistics, 2012. CA Cancer J Clin 62(1):10–29. https://doi.org/10.3322/caac.20138 CrossRefPubMed

Thompson RH, Kuntz SM, Leibovich BC, Dong H, Lohse CM, Webster WS et al (2006) Tumor B7-H1 is associated with poor prognosis in renal cell carcinoma patients with long-term follow-up. Cancer Res 66(7):3381–3385. https://doi.org/10.1158/0008-5472.CAN-05-4303 CrossRefPubMed

Velcheti V, Schalper KA, Carvajal DE, Anagnostou VK, Syrigos KN, Sznol M et al (2014) Programmed death ligand-1 expression in non-small cell lung cancer. Lab Invest 94(1):107–116. https://doi.org/10.1038/labinvest.2013.130 CrossRefPubMed

Wang A, Wang HY, Liu Y, Zhao MC, Zhang HJ, Lu ZY et al (2015) The prognostic value of PD-L1 expression for non-small cell lung cancer patients: a meta-analysis. Eur J Surg Oncol 41(4):450–456. https://doi.org/10.1016/j.ejso.2015.01.020 CrossRefPubMed

Wu C, Zhu Y, Jiang J, Zhao J, Zhang XG, Xu N (2006) Immunohistochemical localization of programmed death-1 ligand-1 (PD-L1) in gastric carcinoma and its clinical significance. Acta Histochem 108(1):19–24. https://doi.org/10.1016/j.acthis.2006.01.003 CrossRefPubMed

Wu CT, Chen WC, Chang YH, Lin WY, Chen MF (2016) The role of PD-L1 in the radiation response and clinical outcome for bladder cancer. Sci Rep 6:19740. https://doi.org/10.1038/srep19740 CrossRefPubMedPubMedCentral

Zhou C, Tang J, Sun H, Zheng X, Li Z, Sun T et al (2017) PD-L1 expression as poor prognostic factor in patients with non-squamous non-small cell lung cancer. Oncotarget 8(35):58457–58468. https://doi.org/10.18632/oncotarget.17022 CrossRefPubMedPubMedCentral

Titel: Expression and clinical significance of PD-L1 and c-Myc in non-small cell lung cancer
verfasst von: Cuiling Zhou
Gang Che
Xiaobin Zheng
Junlan Qiu
Zhinan Xie
Yunyan Cong
Xiaofeng Pei
Hongyu Zhang
Huanhuan Sun
Haiqing Ma
Publikationsdatum: 20.09.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 11/2019
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-019-03025-8

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