SPINK2 is a prognostic biomarker related to immune infiltration in acute myeloid leukemia

Xiaohe Chen; Lifen Zhao; Tian Yu; Jue Zeng; Ming Chen

SPINK2 is a prognostic biomarker related to immune infiltration in acute myeloid leukemia

Am J Transl Res. 2022 Jan 15;14(1):197-210. eCollection 2022.

Authors

Xiaohe Chen¹, Lifen Zhao², Tian Yu³, Jue Zeng¹, Ming Chen¹

Affiliations

¹ Department of Blood Transfusion, The Third Affiliated Hospital of Wenzhou Medical University Ruian 325200, Zhejiang, China.
² Clinical Laboratory, The Third Affiliated Hospital of Wenzhou Medical University Ruian 325200, Zhejiang, China.
³ Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences Beijing 100730, China.

PMID: 35173838
PMCID: PMC8829596

Abstract

Background: Serine peptidase inhibitor Kazal type 2 (SPINK2) has been reported to be involved in certain cancers. We conducted an in-depth investigation on the role and mechanism of SPINK2 in acute myeloid leukemia (AML).

Methods: The relationship between SPINK2 expression and AML clinicopathologic characteristics was determined using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. Concomitantly, we used Kaplan-Meier survival analysis, as well as univariate and multivariate regression analyses to evaluate SPINK2 as a prognostic marker of AML. Additionally, we annotated the enrichment and function of SPINK2 using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Sets Enrichment Analysis (GSEA). The CIBERSORT algorithm was used to analyze the relationship between SPINK2 expression and immune infiltration.

Results: SPINK2 expression was significantly higher in AML patients compared to healthy individuals (P<0.001). The area under receiver operating characteristic curve in the GSE9476 dataset was 0.660, whereas that in the Genotype-Tissue Expression (GTEx) and TCGA datasets was 0.935. In addition, GSEA also showed that several pathways were enriched in the group with high SPINK2 expression, such as PI3K-AKT signaling, PD-L1 expression, and checkpoint pathways. Analysis of immune infiltration showed that SPINK2 expression was correlated with certain immune infiltrating cells. Cox multivariate analysis revealed that the level of SPINK2 was an independent risk factor for the progression of AML (P<0.001). Moreover, age, M1, M5, M6, and CytoRisk-Poor also affected the progression of AML (P<0.05). The C-index of the nomogram in our internal validation was 0.702.

Conclusion: The high expression of SPINK2 in AML suggests that SPINK2 may play an important role in the immune microenvironment and thus could be a biomarker for diagnosis and prognosis of AML.

Keywords: GEO; Serine peptidase inhibitor Kazal-type 2; TCGA; acute myeloid leukemia; immune cell infiltrate; prognosis.