CRABP2 (Cellular Retinoic Acid Binding Protein 2D): A novel biomarker for the diagnosis and prognosis involved in immune infiltration of lung adenocarcinoma

DaXia Cai ^1,2, Feng Tian ³, DengKe Zhang ¹

⁰Cancer Center, Lishui Central Hospital, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui Hospital of Zhejiang University, Lishui 323000, China.

Journal of Cancer +

|

February 24, 2025

View abstract on PubMed

Summary

Cellular Retinoic Acid Binding Protein 2 (CRABP2) is overexpressed in early lung adenocarcinoma (LUAD) and predicts poor prognosis. High CRABP2 expression may guide immunotherapy selection for LUAD patients.

Area Of Science

Oncology
Molecular Biology
Biomarker Discovery

Background

Overexpression of Cellular Retinoic Acid Binding Protein 2 (CRABP2) is implicated in the progression of various cancers.
Limited comprehensive analyses exist for CRABP2 in lung adenocarcinoma (LUAD), necessitating further investigation.

Purpose Of The Study

To comprehensively analyze the role of CRABP2 in lung adenocarcinoma (LUAD).
To evaluate CRABP2 as a potential diagnostic and prognostic biomarker for LUAD.
To explore the association between CRABP2 expression and response to immune checkpoint inhibitor therapy in LUAD.

Main Methods

Utilized big data mining of public databases (TCGA, GEO, GEPIA2, UALCAN, Kaplan Meier plotter, LinkedOmics, TIMER, CCLE) and online analysis tools.
Conducted in vitro experiments including RNA interference, CCK8 assay, flow cytometry, apoptosis detection, and western blot.
Analyzed plasma samples from 640 LUAD patients and 640 healthy controls.

Main Results

CRABP2 was significantly overexpressed in LUAD tissues and plasma of early-stage LUAD patients compared to controls (p<0.0001).
CRABP2 demonstrated accuracy in predicting early LUAD (AUC=0.839) and high expression correlated with poor Overall Survival and First Progression (p<0.05).
High CRABP2 expression promoted LUAD progression by affecting cell cycle, inhibiting apoptosis, and modulating the immune microenvironment, including differential expression of immune checkpoint molecules.

Conclusions

CRABP2 is a potential valuable biomarker for the diagnosis, treatment, and prognosis of LUAD.
Patients with high CRABP2 expression may respond better to inhibitors targeting CTLA4, LAG3, PDCD1, TIGIT, and IGSF8, but potentially less effectively to CD274, HAVCR2, and PDCD1LG2 inhibitors.
High CRABP2 expression suggests potential benefit from immune checkpoint inhibitor therapy in LUAD.

Keywords:

Biomarker CRABP2(Cellular Retinoic Acid Binding Protein 2) Immune checkpoint LUAD (lung adenocarcinoma) apoptosis cell cycle diagnosis