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 ctRNA of 33.3% (3/9 plasma samples) of GC patients, 23.4% (22/94) of CRC patients, 39% (16/41) of NSCLC patients, 54.5% (6/11) of BC patients and 35.3% (6/17) of PC patients. PD-L1 mRNA was not detected in the cancer-free group (0/9), but this was not significantly different from the cumulative cancer patients (p = 0.0602, Fisher’s Exact Test). The frequency of PD-L1 expression was significantly different among the cancer types we studied (p < 0.0001, Fisher ’s Exact). However, median relative PD-L1 expression was not statistically significantly different (7.0 in GC, 5.6 in CRC, 10 in NSCLC, 7.8 in BC, and 9.1 in PC) (p = 0.258, Median Test).
PD-L1 mRNA can be detected and quantitated in ctRNA of cancer patients. The frequency of PD-L1 expression varies by cancer type, however, when detected in ctRNA, levels of PD-L1 expression do not significantly differ across these cancers. 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.
Liquid Genomics, Inc.
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All authors have declared no conflicts of interest.