Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, 410008, China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China.
Oncol Res. 2023 Dec 28;32(2):261-272. doi: 10.32604/or.2023.042345. eCollection 2023.
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 , 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.
寻找免疫疗法的生物标志物是癌症治疗中的一个紧迫问题。细胞视黄醇结合蛋白 2（CRABP2）是人类肿瘤发生和发展中一个有争议的因素。然而，关于 CRABP2 与免疫治疗反应之间的关系的研究有限。本研究发现在乳腺浸润性癌（BRCA）、皮肤皮肤黑色素瘤（SKCM）、胃腺癌（STAD）和睾丸生殖细胞肿瘤（TGCT）中，CRABP2 与免疫检查点标志物（PD-1、PD-L1 和 CTLA-4）呈负相关。特别是在接受 PD-1 抑制剂治疗的 SKCM 患者中，CRABP2 水平升高预示着预后不良。此外，在单细胞水平上，CRABP2 在癌相关成纤维细胞（CAFs）中的表达上调。CRABP2 的表达与 CAFs 的标志物呈正相关，如 SKCM 中的 MFAP5、PDPN、ITGA11、PDGFRα/β 和 THY1。为了验证 CRABP2 的促肿瘤作用，构建了过表达 CRABP2 的 SKCM 异种移植小鼠模型。这些模型显示肿瘤重量和体积增加。富集分析表明，CRABP2 可能参与 SKCM 的免疫相关途径，如细胞外基质（ECM）受体相互作用和上皮-间充质转化（EMT）。该研究表明，CRABP2 可能通过影响 CAFs 的浸润来调节 SKCM 患者的免疫治疗。总之，本研究为 CRABP2 在免疫治疗反应中的作用提供了新的见解。研究结果表明，CRABP2 可能是 SKCM 患者 PD-1 抑制剂的有前途的生物标志物。需要进一步研究来证实这些发现，并探讨 CRABP2 在免疫治疗中的临床意义。
