Open Access

ARTICLE

CRABP2 regulates infiltration of cancer-associated fibroblasts and immune response in melanoma

SHUANGSHUANG ZENG^1,2, XI CHEN^1,2, QIAOLI YI^1,2, ABHIMANYU THAKUR³, HUI YANG^4,*, YUANLIANG YAN^1,2, SHAO LIU^1,2,*

1 Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, 410008, China
2 National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China
3 Pritzker School of Molecular Engineering, Ben May Department for Cancer Research, University of Chicago, Chicago, IL, USA
4 Department of Pathology, The Second Affiliated Hospital of Shandong First Medical University, Taian, 271000, China

* Corresponding Authors: HUI YANG. Email: ; SHAO LIU. Email:

(This article belongs to the Special Issue: Multi-Omics Approaches for Precision Medicine)

Oncology Research 2024, 32(2), 261-272. https://doi.org/10.32604/or.2023.042345

Received 26 May 2023; Accepted 31 July 2023; Issue published 28 December 2023

Abstract

Finding biomarkers for immunotherapy is an urgent issue in cancer treatment. Cellular retinoic acid-binding protein 2 (CRABP2) is a controversial factor in the occurrence and development of human tumors. However, there is limited research on the relationship between CRABP2 and immunotherapy response. This study found that negative correlations of CRABP2 and immune checkpoint markers (PD-1, PD-L1, and CTLA-4) were observed in breast invasive carcinoma (BRCA), skin cutaneous melanoma (SKCM), stomach adenocarcinoma (STAD) and testicular germ cell tumors (TGCT). In particular, in SKCM patients who were treated with PD-1 inhibitors, high levels of CRABP2 predicted poor prognosis. Additionally, CRABP2 expression was elevated in cancer-associated fibroblasts (CAFs) at the single-cell level. The expression of CRABP2 was positively correlated with markers of CAFs, such as MFAP5, PDPN, ITGA11, PDGFRα/β and THY1 in SKCM. To validate the tumor-promoting effect of CRABP2 in vivo, SKCM xenograft mice models with CRABP2 overexpression have been constructed. These models showed an increase in tumor weight and volume. Enrichment analysis indicated that CRABP2 may be involved in immune-related pathways of SKCM, such as extracellular matrix (ECM) receptor interaction and epithelial-mesenchymal transition (EMT). The study suggests that CRABP2 may regulate immunotherapy in SKCM patients by influencing infiltration of CAFs. In conclusion, this study provides new insights into the role of CRABP2 in immunotherapy response. The findings suggest that CRABP2 may be a promising biomarker for PD-1 inhibitors in SKCM patients. Further research is needed to confirm these findings and to explore the clinical implications of CRABP2 in immunotherapy.

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Supplementary Material

Supplementary Material File

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