Expression of OLR1 gene on tumor-associated macrophages of head and neck squamous cell carcinoma, and its correlation with clinical outcome

ABSTRACT

Head and neck squamous cell carcinoma (HNSCC) is one of the most heavily immune infiltrated human tumors, having distinct immune subtypes associated with different molecular characteristics and clinical outcomes. The tumor microenvironment (TME) of HNSCC which was dominated by tumor-associated macrophages (TAMs) had a relatively inferior prognosis. High levels of oxidized low-density lipoprotein receptor 1 (OLR1) expression are associated with more aggressive and metastatic characteristics in multiple cancers. However, the link between the OLR1 expression and immunosuppression of TME, and the molecular mechanisms which govern intratumoral TAMs behavior are unclear. Here, we performed the transcriptional analysis based on a single-cell RNA-sequencing (scRNA-seq) dataset of HNSCC, and found that the OLR1 expression was specifically enriched on the TAMs. Evaluation of protein expression within histologic sections of primary HNSCC patient samples showed a co-expression pattern of OLR1 and CD68 on macrophages. A total of 498 tumor samples of HNSCC patients from The Cancer Genome Atlas (TCGA) database were also analyzed. Remarkably, OLR1 expression was dramatically higher in HNSCC tissues than that in adjacent normal tissues, and the patients with high levels of OLR1 expression had significantly unfavorable overall survival (Hazard Ratio = 1.724, log-rank P-value = 0.0066) when compared to patients harboring low expression levels of OLR1. In summary, we reported that the specific expression of OLR1 on the TAMs was significantly correlated with poor survival outcomes, revealing that OLR1 could serve as a potential prognosis marker and promising target for immunotherapy in HNSCC.

KEYWORDS:

• scRNA-seq
• HNSCC
• OLR1
• Macrophage
• Biomarker

Author contributions

P.Z. Y.Z. and X.X. performed the analysis and prepared the manuscript with the help of Y.H., M.S., Y.Z., and S.Y.; P.Z. and X.C. supervised the studies, designed the analysis, and revised the manuscript.

Availability of data or materials

The materials of patient cohorts used for the current study were publicly available and can be assessed by the TCGA database (https://portal.gdc.cancer.gov/). The scRNA-seq datasets of head and neck cancer samples could be accessed from NCBI’s Gene Expression Omnibus database (http://www.ncbi.nlm.nih.gov/geo/) through accession number: GSE103322, and GSE139324. The processed data and analysis codes are available upon reasonable request from the corresponding author.

Disclosure statement

No potential conflict of interest was reported by the authors.

Ethics approval and consent to participate

This study was approved by the Institutional Review Board (IRB) of the Peking Union Medical College Hospital (PUMCH) (#S-K795). Patients at the PUMCH consented preoperatively to take part in the study following IRB approval and written informed consent was obtained from all patients enrolled in this study. The age and gender of the human subjects providing samples are listed in Table S1.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/2162402X.2023.2203073

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (81273173 and 82000962), Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS) (2021-I2M-1-023 and 2020-I2M-2-009), Science & Technology Fundamental Resources Investigation Program (2022FY100800), National High Level Hospital Clinical Research Funding (2022-PUMCH-B-094), Beijing Hospitals Authority (QML20211205), Beijing Nova Program (Z211100002121044), and the State Key Laboratory Special Fund (2060204).