Association between apoptosis inhibitor of macrophage and microsatellite instability status in colorectal cancer
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RESEARCH ARTICLE
Association between apoptosis inhibitor of macrophage and microsatellite instability status in colorectal cancer Wen‑juan Huang1†, Xin Wang1†, Meng‑lin Zhang1, Li Li2* and Rui‑tao Wang1*
Abstract Background: The microsatellite instability (MSI) in colorectal cancer (CRC) has a more favorable clinical outcome and is characterized by highly upregulated expression of various immunological checkpoints than microsatellite stable (MSS) tumors. Apoptosis inhibitor of macrophage (AIM) is a circulating protein and circulates throughout the body to remove cellular debris. The aim of this study was to evaluate the association between MSI status and AIM levels in CRC patients. Methods: In this study, we evaluated the levels of AIM by Enzyme Linked Immuno-Sorbent Assay (ELISA) in serum of 430 CRC patients. All patients’ clinical and laboratory characteristics at initial diagnosis were collected. The relationship between AIM levels and MSI status was examined. Results: 64 patients (14.9%) were identified as having MSI-H (high-frequency MSI) and 366 casess (85.1%) having MSS. Patients with an MSI-H phenotype had lower AIM levels compared with MSS patients. Moreover, AIM levels were correlated with histological type and MSI status. Logistic regression analysis revealed that decreased AIM levels were independently associated with MSI-H phenotype after adjusting confounding factors. Conclusion: Reduced AIM levels are associated with MSI-H subtyping of CRC. Further research on the involvement of AIM in MSI-H CRC is needed. Keywords: Apoptosis inhibitor of macrophage, Microsatellite instability, Colorectal cancer Background Colorectal cancer (CRC) was the third most common malignant cancer and the fourth leading cause of cancerrelated deaths worldwide [1]. Despite the advancement in comprehensive treatment, the long-term survival of CRC patients remains unsatisfactory. More than 20% of CRC patients were diagnosed with distant metastasis at *Correspondence: [email protected]; [email protected] † Wen-juan Huang and Xin Wang contributed equally to this work 1 Department of Internal Medicine, Harbin Medical University Cancer Hospital, Harbin Medical University, No. 150 Haping ST, Nangang District, Harbin, Heilongjiang 150081, China 2 Department of Colorectal Surgery, Harbin Medical University Cancer Hospital, Harbin Medical University, No. 150 Haping ST, Nangang District, HarbinHeilongjiang 150081, China
initial diagnosis [2]. The microsatellite instability (MSI) subtype of CRC accounts for approximately 15% of colorectal cancers and results from the accumulation of frameshift mutations in target gene caused by a failure of the mismatch repair system [3]. MSI CRCs exhibit proximal colonic location, increased lymphocytic infiltration, and poorer response to chemotherapeutic drugs, and are characterized by highly upregulated expression of various immunological checkpoints [4, 5]. Apoptosis inhibitor of macrophage (AIM) is a circulating protein of approximately 40 kDa and mainly produced by tissue-resid
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