Vertical level of blood cell division cycle 42 predicts response and survival benefits to PD-1 inhibitor-based regimen in metastatic colorectal cancer patients

Abstract

Cell division cycle 42 (CDC42) regulates the development of colorectal cancer (CRC) by modulating cancer malignant behaviors and facilitating immune escape. Hence, this study aimed to explore the correlation of blood CDC42 with treatment response and survival benefit to programmed cell death-1 (PD-1) inhibitor-based regimens in inoperable metastatic CRC (mCRC) patients. Fifty-seven inoperable mCRC patients who received PD-1 inhibitor-based regimens were recruited. The CDC42 in peripheral blood mononuclear cell (PBMC) was detected using RT-qPCR in inoperable mCRC patients at baseline and after 2-cycle treatment. Besides, PBMC CDC42 in 20 healthy controls (HCs) was also detected. CDC42 was higher in inoperable mCRC patients compared to HCs (p < 0.001). Elevated CDC42 was related to a higher performance status score (p = 0.034), multiple metastatic sites (p = 0.028), and the presence of liver metastasis (p = 0.035) in inoperable mCRC patients. During the 2-cycle treatment, CDC42 was reduced (p < 0.001). Higher CDC42 at baseline (p = 0.016) and after 2-cycle treatment (p = 0.002) were both linked with decreased objective response rate. CDC42 high at baseline was related to shorter progression-free survival (PFS) (p = 0.015) and overall survival (OS) (p = 0.050). Moreover, CDC42 high after 2-cycle treatment was also related to unfavorable PFS (p < 0.001) and OS (p = 0.001). After adjustment using multivariate Cox’s analyses, CDC42 high after 2-cycle treatment independently related to shorter PFS (hazard ratio (HR): 4.129, p < 0.001), and CDC42 reduction ≤230% also independently correlated with shorter OS (HR: 4.038, p < 0.001). The longitudinal change of blood CDC42 during PD-1 inhibitor-based regimen estimates treatment response and survival in inoperable mCRC patients.