Circulating tumor cells in pulmonary vein and peripheral arterial provide a metric for PD-L1 diagnosis and prognosis of patients with non-small cell lung cancer

PLoS One. 2019 Jul 26;14(7):e0220306. doi: 10.1371/journal.pone.0220306. eCollection 2019.

Abstract

Background: Lung cancer is the leading cause of death caused by malignant tumors. PD-L1(programmed cell death protein-1) has shown tremendous achievement in treating NSCLC. We sought to find the relationship between CTCs in the pulmonary vein and postoperative PFS, besides we detected PD-L1 in CTCs.

Method: We enrolled 112 NSCLC patients. CTC tests were performed at four time points (preoperative, pulmonary vein, intraoperative and postoperative) on every NSCLC patient who received surgery. The RNA of PD-L1 was tested by FISH. The levels of the PD-L1 mRNA and protein in tissue samples were detected.

Results: The CTCs in the PV were the highest (P< 0.001), and CTCs in the PPA were the lowest (P< 0.001). The PFS in the group with PV CTCs≥ 16/5 ml was shorter than that in the group with PV CTCs< 16/5 ml (11.1 months vs 21.2 months, respectively; P< 0.001). The PFS in the group with PPA CTCs≥ 3/5 ml was shorter than that in the group with CTCs< 3/5 ml (14.8 months vs 20.7 months, respectively; P< 0.001). The CTCs in stage I were lower than those in stage II-IV (P = 0.025). No linear relationship was found between the CTCs and tumor size (P> 0.05) or LN metastasis (P> 0.05). In total, fifty-two (50.5%) patients had positive PD-L1 expression in CTC. In PD-L1-positive CTC patients, the value of PD-L1 tissue expression was higher than that in PD-L1-negative CTC patients (P = 0.0153).

Conclusion: CTCs in the pulmonary vein can be an effective prognosis indicator of NSCLC patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B7-H1 Antigen / genetics*
  • B7-H1 Antigen / metabolism*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Non-Small-Cell Lung / diagnosis*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Early Detection of Cancer
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • In Situ Hybridization, Fluorescence
  • Lung Neoplasms / diagnosis*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Neoplastic Cells, Circulating / metabolism*
  • Neoplastic Cells, Circulating / pathology
  • Prognosis
  • Survival Analysis

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human

Grants and funding

This work was supported by the Department of Science and Technology of Sichuan Province, 2018SZ0152 to JD and the Health and Family Planning Commission of Sichuan Province (CN), 18PJ432 to JD. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.