Frequencies and expression levels of programmed death ligand 1 (PD-L1) in circulating tumor RNA (ctRNA) in various cancer types

Precision medicine and prediction of therapeutic response requires monitoring potential biomarkers before and after treatment. Liquid biopsies provide noninvasive prognostic markers such as circulating tumor DNA and RNA. Circulating tumor RNA (ctRNA) in blood is also used to identify mutations in genes of interest, but additionally, provides information about relative expression levels of important genes. In this study, we analyzed PD-L1 expression in ctRNA isolated from various cancer types. Tumors inhibit antitumor response by modulating the immune checkpoint proteins programmed death ligand 1 (PD-L1) and its cognate receptor PD1. The expression of these genes has been implicated in evasion of immune response and resistance to targeted therapies.

Blood samples were collected from gastric (GC), colorectal (CRC), lung (NSCLC), breast (BC), prostate cancer (PC) patients, and a healthy control group. ctRNA was purified from fractionated plasma, and following reverse transcription, levels of PD-L1 expression were analyzed using qPCR.

PD-L1 expression was detected in the plasma ctRNA of all cancer types at varying frequencies but no PD-L1 mRNA was detected in cancer-free individuals. The frequencies of PD-L1 expression were significantly different among the various cancer types but the median relative PD-L1 expression values were not significantly different. In 12 cases where plasma and tumor tissue were available from the same patients, there was a high degree of concordance between expression of PD-L1 protein in tumor tissues and PD-L1 gene expression in plasma, and both methods were equally predictive of response to nivolumab.

PD-L1 mRNA can be detected and quantitated in ctRNA of cancer patients. These results pave the way for further studies aimed at determining whether monitoring the levels of PD-L1 mRNA in blood can identify patients who are most likely to benefit from the conventional treatment.

Biochemical and biophysical research communications. 2018 Apr 18 [Epub ahead of print]

Toshiyuki Ishiba, Andreas-Claudius Hoffmann, Joshua Usher, Yahya Elshimali, Todd Sturdevant, Mai Dang, Yolanda Jaimes, Rama Tyagi, Ronald Gonzalez, Mary Grino, Jacek K Pinski, Afsaneh Barzi, Luis E Raez, Wilfried E Eberhardt, Dirk Theegarten, Heinz-Josef Lenz, Hiroyuki Uetake, Peter V Danenberg, Kathleen Danenberg

Liquid Genomics, Inc., 9920 Jefferson Blvd, Culver City, CA, United States; Department of Biochemistry and Molecular Medicine, Keck-USC School of Medicine, University of Southern California, 1975 Zonal Ave, Los Angeles, CA, United States; Department of Surgical Specialties, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, Japan., Liquid Genomics, Inc., 9920 Jefferson Blvd, Culver City, CA, United States; Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Hufelandstrasse 55, Essen, Germany., Liquid Genomics, Inc., 9920 Jefferson Blvd, Culver City, CA, United States; Keck School of Medicine at USC, Division of Biostatistics, 1975 Zonal Ave, Los Angeles, CA, United States., Liquid Genomics, Inc., 9920 Jefferson Blvd, Culver City, CA, United States., Department of Medicine, Division of Oncology, Keck School of Medicine, Norris Comprehensive Cancer Center, 1975 Zonal Ave, Los Angeles, CA, United States., Memorial Cancer Institute, 801 N Flamingo Road Suite 11, Pembroke Pines, FL, United States., Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Hufelandstrasse 55, Essen, Germany., Institute of Pathology, University Hospital Essen, University Duisburg-Essen, Hufelandstrasse 55, Essen, Germany., Department of Biochemistry and Molecular Medicine, Keck-USC School of Medicine, University of Southern California, 1975 Zonal Ave, Los Angeles, CA, United States., Department of Surgical Specialties, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, Japan., Department of Biochemistry and Molecular Medicine, Keck-USC School of Medicine, University of Southern California, 1975 Zonal Ave, Los Angeles, CA, United States. Electronic address: .