Journal of Chest Surgery

The Korean Society for Thoracic and Cardiovascular Surgery (대한심장혈관흉부외과학회)
권호 표지
DOI QR코드

DOI QR Code

Prognostic Role of Circulating Tumor Cells in the Pulmonary Vein, Peripheral Blood, and Bone Marrow in Resectable Non-Small Cell Lung Cancer

  • Lee, Jeong Moon (Department of Thoracic and Cardiovascular Surgery, Wonkwang University School of Medicine) ;
  • Jung, Woohyun (Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital) ;
  • Yum, Sungwon (Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital) ;
  • Lee, Jeong Hoon (Division of Biomedical Informatics, Seoul National University Biomedical Informatics, Seoul National University College of Medicine) ;
  • Cho, Sukki (Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital)
  • Received : 2021.11.17
  • Accepted : 2022.03.02
  • Published : 2022.06.05
Download PDF
⟨ Previous Next ⟩

Abstract

Background: Studies of the prognostic role of circulating tumor cells (CTCs) in early-stage non-small cell lung cancer (NSCLC) are still limited. This study investigated the prognostic power of CTCs from the pulmonary vein (PV), peripheral blood (PB), and bone marrow (BM) for postoperative recurrence in patients who underwent curative resection for NSCLC. Methods: Forty patients who underwent curative resection for NSCLC were enrolled. Before resection, 10-mL samples were obtained of PB from the radial artery, blood from the PV of the lobe containing the tumor, and BM aspirates from the rib. A microfabricated filter was used for CTC enrichment, and immunofluorescence staining was used to identify CTCs. Results: The pathologic stage was stage I in 8 patients (20%), II in 15 (38%), III in 14 (35%), and IV in 3 (8%). The median number of PB-, PV-, and BM-CTCs was 4, 4, and 5, respectively. A time-dependent receiver operating characteristic curve analysis showed that PB-CTCs had excellent predictive value for recurrence-free survival (RFS), with the highest area under the curve at each time point (first, second, and third quartiles of RFS). In a multivariate Cox proportional hazard regression model, PB-CTCs were an independent risk factor for recurrence (hazard ratio, 10.580; 95% confidence interval, 1.637-68.388; p<0.013). Conclusion: The presence of ≥4 PB-CTCs was an independent poor prognostic factor for RFS, and PV-CTCs and PB-CTCs had a positive linear correlation in patients with recurrence.

Keywords

Acknowledgement

This work was supported by the SNUBH Research Fund (grant no., 02-2014-068).

References

  1. Goldstraw P, Chansky K, Crowley J, et al. The IASLC Lung Cancer Staging Project: proposals for revision of the TNM stage groupings in the forthcoming (eighth) edition of the TNM classification for lung cancer. J Thorac Oncol 2016;11:39-51. https://doi.org/10.1016/j.jtho.2015.09.009
  2. Hung JJ, Jeng WJ, Hsu WH, et al. Prognostic factors of postrecurrence survival in completely resected stage I non-small cell lung cancer with distant metastasis. Thorax 2010;65:241-5. https://doi.org/10.1136/thx.2008.110825
  3. Kim MY, Oskarsson T, Acharyya S, et al. Tumor self-seeding by circulating cancer cells. Cell 2009;139:1315-26. https://doi.org/10.1016/j.cell.2009.11.025
  4. Cristofanilli M, Budd GT, Ellis MJ, et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med 2004;351:781-91. https://doi.org/10.1056/NEJMoa040766
  5. Cohen SJ, Punt CJ, Iannotti N, et al. Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J Clin Oncol 2008;26:3213-21. https://doi.org/10.1200/JCO.2007.15.8923
  6. Sequist LV, Nagrath S, Toner M, Haber DA, Lynch TJ. The CTC-chip: an exciting new tool to detect circulating tumor cells in lung cancer patients. J Thorac Oncol 2009;4:281-3. https://doi.org/10.1097/jto.0b013e3181989565
  7. de Bono JS, Scher HI, Montgomery RB, et al. Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin Cancer Res 2008;14:6302-9. https://doi.org/10.1158/1078-0432.ccr-08-0872
  8. Gallagher DJ, Milowsky MI, Ishill N, et al. Detection of circulating tumor cells in patients with urothelial cancer. Ann Oncol 2009;20:305-8. https://doi.org/10.1093/annonc/mdn627
  9. Hashimoto M, Tanaka F, Yoneda K, et al. Significant increase in circulating tumour cells in pulmonary venous blood during surgical manipulation in patients with primary lung cancer. Interact Cardiovasc Thorac Surg 2014;18:775-83. https://doi.org/10.1093/icvts/ivu048
  10. Reddy RM, Murlidhar V, Zhao L, et al. Pulmonary venous blood sampling significantly increases the yield of circulating tumor cells in early-stage lung cancer. J Thorac Cardiovasc Surg 2016;151:852-8. https://doi.org/10.1016/j.jtcvs.2015.09.126
  11. Hashimoto M, Tanaka F, Yoneda K, et al. Positive correlation between postoperative tumor recurrence and changes in circulating tumor cell counts in pulmonary venous blood (pvCTC) during surgical manipulation in non-small cell lung cancer. J Thorac Dis 2018;10:298-306. https://doi.org/10.21037/jtd.2017.12.56
  12. Lv C, Zhao B, Wang L, et al. Detection of circulating tumor cells in pulmonary venous blood for resectable non-small cell lung cancer. Oncol Lett 2018;15:1103-12.
  13. Grobe A, Blessmann M, Hanken H, et al. Prognostic relevance of circulating tumor cells in blood and disseminated tumor cells in bone marrow of patients with squamous cell carcinoma of the oral cavity. Clin Cancer Res 2014;20:425-33. https://doi.org/10.1158/1078-0432.CCR-13-1101
  14. Molloy TJ, Bosma AJ, Baumbusch LO, et al. The prognostic significance of tumour cell detection in the peripheral blood versus the bone marrow in 733 early-stage breast cancer patients. Breast Cancer Res 2011;13:R61. https://doi.org/10.1186/bcr2898
  15. Kim EH, Lee JK, Kim BC, et al. Enrichment of cancer cells from whole blood using a microfabricated porous filter. Anal Biochem 2013;440:114-6. https://doi.org/10.1016/j.ab.2013.05.016
  16. Rahman MS, Sultana M. Performance of Firth-and logF-type penalized methods in risk prediction for small or sparse binary data. BMC Med Res Methodol 2017;17:33. https://doi.org/10.1186/s12874-017-0313-9
  17. Xu T, Shen G, Cheng M, Xu W, Shen G, Hu S. Clinicopathological and prognostic significance of circulating tumor cells in patients with lung cancer: a meta-analysis. Oncotarget 2017;8:62524-36. https://doi.org/10.18632/oncotarget.19122
  18. Berezovskaya O, Schimmer AD, Glinskii AB, et al. Increased expression of apoptosis inhibitor protein XIAP contributes to anoikis resistance of circulating human prostate cancer metastasis precursor cells. Cancer Res 2005;65:2378-86. https://doi.org/10.1158/0008-5472.CAN-04-2649
  19. Luzzi KJ, MacDonald IC, Schmidt EE, et al. Multistep nature of metastatic inefficiency: dormancy of solitary cells after successful extravasation and limited survival of early micrometastases. Am J Pathol 1998;153:865-73. https://doi.org/10.1016/S0002-9440(10)65628-3
  20. Gabrielson A, Wu Y, Wang H, et al. Intratumoral CD3 and CD8 T-cell densities associated with relapse-free survival in HCC. Cancer Immunol Res 2016;4:419-30. https://doi.org/10.1158/2326-6066.CIR-15-0110
  21. Morvan MG, Lanier LL. NK cells and cancer: you can teach innate cells new tricks. Nat Rev Cancer 2016;16:7-19. https://doi.org/10.1038/nrc.2015.5
  22. Ye L, Zhang F, Li H, et al. Circulating tumor cells were associated with the number of T lymphocyte subsets and NK cells in peripheral blood in advanced non-small-cell lung cancer. Dis Markers 2017;2017:5727815.
  23. Meads MB, Hazlehurst LA, Dalton WS. The bone marrow microenvironment as a tumor sanctuary and contributor to drug resistance. Clin Cancer Res 2008;14:2519-26. https://doi.org/10.1158/1078-0432.ccr-07-2223
  24. Meng S, Tripathy D, Frenkel EP, et al. Circulating tumor cells in patients with breast cancer dormancy. Clin Cancer Res 2004;10:8152-62. https://doi.org/10.1158/1078-0432.ccr-04-1110
  25. Mehes G, Witt A, Kubista E, Ambros PF. Circulating breast cancer cells are frequently apoptotic. Am J Pathol 2001;159:17-20. https://doi.org/10.1016/S0002-9440(10)61667-7
  26. Pantel K, Brakenhoff RH, Brandt B. Detection, clinical relevance and specific biological properties of disseminating tumour cells. Nat Rev Cancer 2008;8:329-40. https://doi.org/10.1038/nrc2375
  27. Tian D, Pei Y, Zheng Q, et al. Effect of visceral pleural invasion on the prognosis of patients with lymph node negative non-small cell lung cancer. Thorac Cancer 2017;8:97-105. https://doi.org/10.1111/1759-7714.12412