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PD-L1 Expression is not a Predictive Factor for Recurrence in Resected Non-small Cell Lung Cancer

  • Lung Cancer
  • Published:
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Abstract

Purpose

Although targeting programmed death-1 (PD-1) and its ligand, programmed death-ligand 1 (PD-L1), is an established treatment modality for non-small cell lung cancer (NSCLC), the prognostic relevance of PD-L1 expression in NSCLC patients who undergo pulmonary resection is controversial.

Methods

Two hundred thirty-seven NSCLC patients who underwent pulmonary resection were enrolled and the relationship between PD-L1 and various clinicopathological factors, as well as the prognostic relevance of PD-L1, was evaluated.

Results

PD-L1 expression was significantly higher in male patients (p < 0.01), lymphatic invasion (p < 0.01), vascular invasion (p < 0.01), grade 3–4 differentiation (p < 0.01), squamous cell carcinoma (p < 0.01), and pathological stage > II (p < 0.01), but significantly lower in those who were epithelial growth factor receptor (EGFR) mutation negative (p < 0.01). Relapse-free survival was significantly worse in patients with PD-L1 expression (p = 0.04). Univariate analysis showed that male sex (p = 0.04), carcinoembryonic antigen expression (CEA) (p < 0.01), maximum standardized uptake value (p < 0.01), lymphatic invasion (p < 0.01), vascular invasion (p < 0.01), grade 3–4 differentiation (p < 0.01), lower lobe disease (p = 0.04), PD-L1 expression (p = 0.03), and pathological stage (p < 0.01) were significant risk factors of recurrence. In multivariate analysis, CEA expression (p = 0.01), lymphatic invasion (p = 0.04), and pathological stage (p < 0.01) were risk factors for recurrence, whereas PD-L1 expression was not a significant factor of recurrence (p = 0.62).

Conclusion

PD-L1 expression was not a risk factor of recurrence but tumor progression tended to increase PD-L1 expression.

Trial Registration

The Institutional Review Board of Kanazawa Medical University approved the protocol of this retrospective study (approval number: I392), and written informed consent was obtained from all patients.

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Data Availability

The datasets generated and/or analyzed during the current study are not publicly available due to (our institutional restrictions, e.g., them containing information that could compromise research participant privacy/consent), but are available from the corresponding author on reasonable request.

References

  1. Siegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2018. CA Cancer J Clin 68:7–30

    Article  PubMed  Google Scholar 

  2. Brahmer J, Reckamp KL, Baas P, Crinò L, Eberhardt WEE, Poddubskaya E et al (2015) Nivolumab versus docetaxel in advanced squamous-cell non–small-cell lung cancer. N Engl J Med 373:123–135

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP et al (2015) Pembrolizumab for the treatment of non–small-cell lung cancer. N Engl J Med 372:2018–2028

    Article  PubMed  Google Scholar 

  4. Fehrenbacher L, Spira A, Ballinger M, Kowanetz M, Vansteenkiste J, Mazieres J, Park K et al (2016) Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet 387:1837–1846

    Article  CAS  PubMed  Google Scholar 

  5. Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE et al (2015) Nivolumab versus docetaxel in advanced nonsquamous non–small-cell lung cancer. N Engl J Med 373:1627–1639

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Sun JM, Zhou W, Choi YL, Choi SJ, Kim SE, Wang Z et al (2016) Prognostic significance of PD-L1 in patients with non-small cell lung cancer: a large cohort study of surgically resected cases. J Thorac Oncol 11:1003–1011

    Article  CAS  PubMed  Google Scholar 

  7. 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 8:58457–58468

    Article  PubMed  PubMed Central  Google Scholar 

  8. Tuminello S, Sikavi D, Veluswamy R, Gamarra C, Lieberman-Cribbin W, Flores R et al (2020) PD-L1 as a prognostic biomarker in surgically resectable non-small cell lung cancer: a meta-analysis. Transl Lung Cancer Res 9:1343–1360

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Zhao Y, Shi F, Zhou Q, Li Y, Wu J, Wang R et al (2020) Prognostic significance of PD-L1 in advanced non-small cell lung carcinoma. Medicine 99:45

    Google Scholar 

  10. Kojima K, Sakamoto T, Kasai T, Kagawa T, Yoon H, Atagi S (2021) PD-L1 expression as a predictor of postoperative recurrence and the association between the PD-L1 expression and EGFR mutations in NSCLC. Sci Rep 11:17522

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Eichhorn F, Kriegsmann M, Klotz L, Kriegsmann K, Muley T, Zgorzelski C et al (2021) Prognostic impact of PD-L1 expression in pN1 NSCLC: a retrospective single-center analysis. Cancers 13:2046

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Yang CY, Lin MW, Chang YL, Wu CT, Yang PC (2014) Programmed cell death-ligand 1 expression in surgically resected stage I pulmonary adenocarcinoma and its correlation with driver mutations and clinical outcomes. Eur J Cancer 50:1319–1361

    Article  Google Scholar 

  13. Velcheti V, Schalper KA, Carvajal DE, Anagnostou VA, Syrigos KN, Sznol M et al (2014) Programmed death ligand-1 expression in non-small cell lung cancer. Lab Invest 94:107–116

    Article  CAS  PubMed  Google Scholar 

  14. Marti AM, Martinez P, Navarro A, Cedres S, Murtra-Garrell N, Sansano FS et al (2014) Concordance of PD-L1 expression by different immunohistochemistry (IHC) definitions and in situ hybridization (ISH) in squamous cell carcinoma (SCC) of the lung. J Clin Oncol 32:7569

    Article  Google Scholar 

  15. 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. Clin Cancer Res 10:5094–5100

    Article  CAS  PubMed  Google Scholar 

  16. Brinkman GL, Coates EO (1963) The effect of bronchitis, smoking, and occupation on ventilation. Am Rev Respir Dis 87:684–693

    CAS  PubMed  Google Scholar 

  17. Li D, Yuan X, Liu J, Li C, Li W (2018) Prognostic value of prognostic nutritional index in lung cancer: a meta-analysis. J Thorac Dis 10:5298–5307

    Article  PubMed  PubMed Central  Google Scholar 

  18. Qiu C, Qu X, Shen X, Zheng C, Zhu L, Meng L et al (2015) Evaluation of prognostic nutritional index in patients undergoing radical surgery with nonsmall cell lung. Cancer Nutr Cancer 67:741–747

    Article  PubMed  Google Scholar 

  19. Zahorec R (2001) Ratio of neutrophil to lymphocyte counts: rapid and simple parameter of systemic inflammation and stress in critically ill. Bratisl Lek Listy 102:5–14

    CAS  PubMed  Google Scholar 

  20. Shimizu K, Okita R, Saisho S, Maeda A, Nojima Y, Nakata M (2015) Preoperative neutrophil/lymphocyte ratio and prognostic nutritional index predict survival in patients with non-small cell lung cancer. World J Surg Oncol 13:291

    Article  PubMed  PubMed Central  Google Scholar 

  21. Mizuguchi S, Izumi N, Tsukioka T, Komatsu H, Nishiyama N (2018) Neutrophil-lymphocyte ratio predicts recurrence in patients with resected stage 1 non-small cell lung cancer. J Cardiothorac Surg 13:78

    Article  PubMed  PubMed Central  Google Scholar 

  22. Vrankar M, Kern I, Stanic K (2020) Prognostic value of PD-L1 expression in patients with unresectable stage III non-small cell lung cancer treated with chemoradiotherapy. Radiat Oncol 15:247

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Qu J, Jiang M, Wang L, Zhao D, Qin K, Wang Y et al (2020) Mechanism and potential predictive biomarkers of immune checkpoint inhibitors in NSCLC. Biomed Pharmacother 127:109996

    Article  CAS  PubMed  Google Scholar 

  24. Felip E, Altorki N, Zhou C, Csőszi T, Vynnychenko I, Goloborodko O et al (2021) Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (Impower010): a randomized, multicentre, open-label, phase 3 trial. Lancet 398:1344–1357

    Article  CAS  PubMed  Google Scholar 

  25. Takada K, Okamoto T, Shoji F, Shimokawa M, Akamine T, Takamori S et al (2016) Prognostic impact of controlling nutritional status score in resected lung squamous cell carcinoma. J Thorac Oncol 11:1879–1890

    Article  PubMed  Google Scholar 

  26. Miyazawa T, Marushima H, Saji H, Kojima K, Hoshikawa M, Takagi M et al (2019) PD-L1 expression in non-small-cell lung cancer including various adenocarcinoma subtypes. Ann Thorac Cardiovasc Surg 25:1–9

    Article  PubMed  Google Scholar 

  27. 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 89:181–188

    Article  PubMed  Google Scholar 

  28. D’lncecco A, Andreozzi M, Ludovini V, Rossi E, Capodanno A, Landi L, et al (2015) PD-1 and PD-l1 expression in molecularly selected non-small-cell lung cancer patients. Br J Cancer 112:95–102

    Article  PubMed  Google Scholar 

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Acknowledgements

We thank H. Nikki March, PhD, from Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.

Funding

This study has not been funded.

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Authors and Affiliations

  1. Department of Thoracic Surgery, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa, 920-0293, Japan

    Nozomu Motono, Takaki Mizoguchi, Masahito Ishikawa, Shun Iwai, Yoshihito Iijima & Hidetaka Uramoto

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  1. Nozomu Motono
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  2. Takaki Mizoguchi
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  3. Masahito Ishikawa
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  5. Yoshihito Iijima
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Contributions

NM performed the research, collected and analyzed the data, and wrote the paper. TM, MI, SI, and YI contributed to sample collection. HU contributed to supervision of this study and revision of the manuscript. All authors have read and approved the manuscript and ensure that this is the case.

Corresponding author

Correspondence to Nozomu Motono.

Ethics declarations

Competing interests

The authors declare that they have no competing interests.

Ethical Approval

The present study was conducted in accordance with the amended Declaration of Helsinki. The Institutional Review Boards of Kanazawa Medical University approved the protocol (approval number: I392).

Informed Consent

Written informed consent was obtained from all of the patients.

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Not applicable.

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Motono, N., Mizoguchi, T., Ishikawa, M. et al. PD-L1 Expression is not a Predictive Factor for Recurrence in Resected Non-small Cell Lung Cancer. Lung 201, 95–101 (2023). https://doi.org/10.1007/s00408-022-00593-4

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  • DOI: https://doi.org/10.1007/s00408-022-00593-4

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