The mRNA Expression Profile of PD-1 and PD-L1 in Peripheral Blood of Colorectal Cancer Patients

Abstract

Background: Immunotherapy using immune checkpoint inhibitors has currently emerged as an effective treatment for a subset of colorectal cancer (CRC) patients. The roles of PD-1 and PD-L1 expression levels in peripheral blood to predict patient’s response to immune checkpoint inhibitors are not well established. Therefore, we analyzed PD-1 and PD-L1 mRNA expression levels of peripheral blood in Indonesian CRC patients and explored the association with the clinicopathological features.Methods: Peripheral blood of 25 CRC patients and 10 healthy individuals were collected in Dharmais Hospital-National Cancer Center from 2017 to 2018. PD-1 and PD-L1 mRNA expression levels were analyzed using real time PCR. The associations with clinicopathological variables were analyzed with fisher-exact test or chi square test.Results: PD-1 mRNA expression levels were significantly lower in CRC patients compared to healthy individuals (HI) (mean: 0.0015 ± 0.0013 and 0.017 ± 0.010 respectively, p < 0.001). Although PD-L1 mRNA expression levels were lower in CRC patients, the difference was not statistically significant (mean in CRC and HI: 0.021 ± 0.013 and 0.034 ± 0.028 respectively, p = 0.125). The expression of PD-L1 was higher in CRC females compared to males (p = 0.03). The expression levels of PD-L1 were not associated with different ages (p = 0.673), stages (p = 0.298), histological type of colorectal cancer (p=0.852), patient status (p = 1.000), and body mass index (p = 0.514).Conclusions: The mRNA expression levels of PD-1 and PD-L1 were lower in CRC patients compared to healthy controls. Expression of PD-L1 were correlated with sex, but not correlated with ages, stages, histological type of CRC, patient status, and body mass index.

Programmed death protein 1 (PD1) mRNA expression as a screening and diagnostic tool in colon cancer

“…A contradicting result to what we have found, Ajoedi et al who documented that PD-1 mRNA expression decreased in peripheral blood of CRC patients compared to healthy individuals. PD-1 expression tends to be low in CRC with advanced stages [39].…”

Assessment of PD-L1 mRNA expression in gastrointestinal tumors and the response to immunotherapy

“…For instance, PD-L1 mRNA expression in platelet and exosomes also contribute to predicting the clinical response to immunotherapy ( 29 ), the measurement of PD-L1 mRNA expression in tumor tissue by RNA-seq is analytically and clinically in predicting the immune checkpoint inhibitor response ( 30 ), and blood expressed PD-L1 mRNA level was confirmed to be associated with anti–PD-1 response ( 12 – 14 ). Moreover, compared with the healthy controls, tissue PD-L1 mRNA expression decreased in patients with colorectal cancer ( 31 ) and could successfully discriminate the worse progression-free survival of those patients with colorectal cancer liver metastases who adopted neoadjuvant-treatment ( 32 ). However, some literature studies express the opposite view and reported that no statistically significant difference in the PD-L1 mRNA expression between responders and non-responders to immunotherapy was observed ( 33 ).…”

Investigation of Dextran-Coated Superparamagnetic Nanoparticles for Targeted Vinblastine Controlled Release, Delivery, Apoptosis Induction, and Gene Expression in Pancreatic Cancer Cells

“…Total RNA was classically used in the cDNA synthesis kit (Fermentas, Germany). According to the instructions of the manufacturer of the kit, five pairs of oligonucleotide primers for targets and endogenous genes were used and referenced [ 35 , 36 , 37 , 38 , 39 ], as illustrated in Table 1 .…”