TY - JOUR
T1 - CD45+CD326+ cells are predictive of poor prognosis in non-small cell lung cancer patients
AU - Ishizawa, Kota
AU - Yamanaka, Mie
AU - Saiki, Yuriko
AU - Miyauchi, Eisaku
AU - Fukushige, Shinichi
AU - Akaishi, Tetsuya
AU - Asao, Atsuko
AU - Mimori, Takahiro
AU - Saito, Ryota
AU - Tojo, Yutaka
AU - Yamashita, Riu
AU - Abe, Michiaki
AU - Sakurada, Akira
AU - Pham, Nhu An
AU - Li, Ming
AU - Okada, Yoshinori
AU - Ishii, Tadashi
AU - Ishii, Naoto
AU - Kobayashi, Seiichi
AU - Nagasaki, Masao
AU - Ichinose, Masakazu
AU - Tsao, Ming Sound
AU - Horii, Akira
N1 - Funding Information:
We are grateful to Dr. Barbara Lee Smith Pierce (Adjunct Professor, University of Maryland University College) for her editorial work in the preparation of the manuscript. We gratefully acknowledge Drs. Makoto Kobayashi, Osamu Usami, Taizo Hirano, Naoki Tode, Teruyuki Sato, Tomohiro Ichikawa, Yusaku Sasaki, and Tatsuma Okazaki from Department of Respiratory Medicine, Tohoku University, and Ms. Chiharu Kudo, Drs. Hikari Sato, and Yoshikazu Okubo from Japanese Red Cross Ishinomaki Hospital, for their collection of patients' samples. We are also grateful to Biomedical Research Core, Tohoku University School of Medicine for their technical supports. This work was supported in part by Grants-in-Aid for Scientific Research (JP17K09641, 26460468, and 17K17589) from the Japan Society for the Promotion of Science.
Publisher Copyright:
© 2019 American Association for Cancer Research.
PY - 2019/11/15
Y1 - 2019/11/15
N2 - Purpose: The epithelial-to-mesenchymal transition, the major process by which some cancer cells convert from an epithelial phenotype to a mesenchymal one, has been suggested to drive chemo-resistance and/or metastasis in patients with cancer. However, only a few studies have demonstrated the presence of CD45/CD326 doubly-positive cells (CD45/CD326 DPC) in cancer. We deployed a combination of cell surface markers to elucidate the phenotypic heterogeneity in non-small cell lung cancer (NSCLC) cells and identified a new subpopulation that is doubly-positive for epithelial and non-epithelial cell-surface markers in both NSCLC cells and patients' malignant pleural effusions. Experimental Design: We procured a total of 39 patients' samples, solid fresh lung cancer tissues from 21 patients and malignant pleural effusion samples from 18 others, and used FACS and fluorescence microscopy to check their surface markers. We also examined the EGFR mutations in patients with known acquired EGFR mutations. Results: Our data revealed that 0.4% to 17.9% of the solid tumor tissue cells and a higher percentage of malignant pleural effusion cells harbored CD45/CD326 DPC expressing both epithelial and nonepithelial surface markers. We selected 3 EGFR mutation patients and genetically confirmed that the newly identified cell population really originated from cancer cells. We also found that higher proportions of CD45/CD326 DPC are significantly associated with poor prognosis. Conclusions: In conclusion, varying percentages of CD45/CD326 DPC exist in both solid cancer tissue and malignant pleural effusion in patients with NSCLC. This CD45/CD326 doubly-positive subpopulation can be an important key to clinical management of patients with NSCLC.
AB - Purpose: The epithelial-to-mesenchymal transition, the major process by which some cancer cells convert from an epithelial phenotype to a mesenchymal one, has been suggested to drive chemo-resistance and/or metastasis in patients with cancer. However, only a few studies have demonstrated the presence of CD45/CD326 doubly-positive cells (CD45/CD326 DPC) in cancer. We deployed a combination of cell surface markers to elucidate the phenotypic heterogeneity in non-small cell lung cancer (NSCLC) cells and identified a new subpopulation that is doubly-positive for epithelial and non-epithelial cell-surface markers in both NSCLC cells and patients' malignant pleural effusions. Experimental Design: We procured a total of 39 patients' samples, solid fresh lung cancer tissues from 21 patients and malignant pleural effusion samples from 18 others, and used FACS and fluorescence microscopy to check their surface markers. We also examined the EGFR mutations in patients with known acquired EGFR mutations. Results: Our data revealed that 0.4% to 17.9% of the solid tumor tissue cells and a higher percentage of malignant pleural effusion cells harbored CD45/CD326 DPC expressing both epithelial and nonepithelial surface markers. We selected 3 EGFR mutation patients and genetically confirmed that the newly identified cell population really originated from cancer cells. We also found that higher proportions of CD45/CD326 DPC are significantly associated with poor prognosis. Conclusions: In conclusion, varying percentages of CD45/CD326 DPC exist in both solid cancer tissue and malignant pleural effusion in patients with NSCLC. This CD45/CD326 doubly-positive subpopulation can be an important key to clinical management of patients with NSCLC.
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U2 - 10.1158/1078-0432.CCR-19-0545
DO - 10.1158/1078-0432.CCR-19-0545
M3 - Article
C2 - 31383733
AN - SCOPUS:85075094241
SN - 1078-0432
VL - 25
SP - 6756
EP - 6763
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 22
ER -
