RAD51Bme Levels as a Potential Predictive Biomarker for PD-1 Blockade Response in Non-Small Cell Lung Cancer

Abstract

Lung cancer (LC) cells frequently express high levels of programmed death-ligand 1 (PD-L1). Although these levels grossly correlate with the likelihood of response to specific checkpoint inhibitors, the response prediction is rather imperfect, and more accurate predictive biomarkers are mandatory. We examined the methylation profile of RAD51B (RAD51Bme) as a candidate predictive biomarker for anti-PD-1 therapy efficacy in non-small cell lung cancer (NSCLC), correlating with patients’ outcome. PD-L1 immunoexpression and RAD51Bme levels were analysed in NSCLC samples obtained from patients not treated with anti-PD-1 (Untreated Cohort (#1)) and patients treated with PD-1 blockade (Treated Cohort (#2)). Of a total of 127 patients assessed, 58.3% depicted PD-L1 positivity (PD-L1+). RAD51Bme levels were significantly associated with PD-L1 immunoexpression. Patients with PD-1 blockade clinical benefit disclosed higher RAD51Bme levels (p = 0.0390) and significantly lower risk of disease progression (HR 0.37; 95% CI: 0.15–0.88; p = 0.025). Combining RAD51Bme+ with PD-L1+ improved the sensitivity of the test to predict immunotherapy response. PD-L1+ was also associated with lower risk of death (HR 0.35; 95% CI: 0.15–0.81; p = 0.014). Thus, RAD51Bme levels might be combined with validated predictive biomarker PD-L1 immunostaining to select patients who will most likely experience clinical benefit from PD-1 blockade. The predictive value of RAD51Bme should be confirmed in prospective studies.

Integration of bioinformatics analysis and experimental validation identifies plasma exosomal miR‐103b/877‐5p/29c‐5p as diagnostic biomarkers for early lung adenocarcinoma

“…Target genes of 280, 650, and 26 were found in the predicted cross points of the four tools, indicating that they may be promising target genes of hsa‐miR‐103b, hsa‐miR‐877‐5p, and hsa‐miR‐29c‐5p. Some of these target genes, such as IL7R, 38 DDR1, 39 FZD3, 40 BCL9, 41 RAD518 42 etc., have been confirmed to be involved in the occurrence and development of lung cancer in previous studies, which also proved that miRNAs may play an important role in the occurrence and development of lung cancer. Go annotation and biosignaling pathway analysis were performed using 280, 650, and 26 target genes to reveal the main regulatory patterns of hsa‐miR‐103b, hsa‐miR‐877‐5p, and hsa‐miR‐29C‐5p.…”

Epigenetic Modification of PD-1/PD-L1-Mediated Cancer Immunotherapy against Melanoma

“…The methylation of RAD51B is correlated with patient outcome in nonsmall-cell lung cancer. RAD51B methylation levels were positively related to high PD-L1 expression [129]. A highly upregulated PD-L1 is related to a favorable clinical response, and patients with PD-1 blockade efficacy had higher RAD51B methylation levels [129].…”

“…RAD51B methylation levels were positively related to high PD-L1 expression [129]. A highly upregulated PD-L1 is related to a favorable clinical response, and patients with PD-1 blockade efficacy had higher RAD51B methylation levels [129]. Therefore, RAD51B methylation stimulants are expected to obtain therapeutic efficacy in anti-PD-1/PD-L1 antibody treatment.…”

The prognostic biological markers of immunotherapy for non-small cell lung cancer: current landscape and future perspective

“…RAD51B me levels were markedly higher in PD-L1-expressing individuals in comparison to PD-L1-negative individuals ( P < 0.05). Furthermore, RAD51B me levels were significantly associated with the response to ICIs, suggesting its potential as a predictive indicator for the efficacy of immunotherapy in NSCLC ( 110 ). Although ICIs have demonstrated efficacy in NSCLC, the benefits of ICIs for individuals with positive driver gene mutations remain inconclusive.…”