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结直肠癌转移相关基因 1 作为一种泛癌预后和免疫生物标志物的潜在作用。

A potential role for metastasis-associated in colon cancer 1 () as a pan-cancer prognostic and immunological biomarker.

机构信息

Department of Oncology & Department of Breast Surgery, The Second Hospital of Dalian Medical University, Dalian 116023, China.

出版信息

Math Biosci Eng. 2021 Sep 23;18(6):8331-8353. doi: 10.3934/mbe.2021413.

Abstract

BACKGROUND

Metastasis-Associated in Colon Cancer 1(MACC1) is a validated biomarker for metastasis and is linked to survival. Although extensive experimental evidence indicates an association between MACC1 and diverse cancers, no pan-cancer analyses have yet been performed for this marker, and the role of MACC1 in immunology remains unknown.

MATERIAL AND METHODS

In our study, we performed the analysis of MACC1 expression and its influence on prognosis using multiple databases, including TIMER2, GEPIA2, Kaplan-Meier plotter. MACC1 promoter methylation levels were evaluated using the UALCAN database. Based on the TCGA database, we explored the relationship between MACC1 and tumor mutational burden (TMB), microsatellite instability (MSI), immune checkpoints using the R programming language. We evaluated the association between MACC1 and immune infiltration via TIMER and UALCAN.

RESULTS

Our results revealed that abnormal DNA methylation may be an important cause for the different expression of MACC1 across cancer types. Meanwhile, we explored the potential oncogenic roles of MACC1 and found significant prognostic value. MACC1 may be related to T-cell function and the polarization of tumor-associated macrophages, especially in STAD and LGG. Its expression was associated with immune infiltration and was found to be closely related to immune checkpoint-associated genes, especially CD274 and SIGLEC15, indicating that MACC1 may be a potential immune therapeutic target for several malignancies. Our paper reveals for the first time the relationship between MACC1 and cancer immunology.

CONCLUSIONS

MACC1 might act as a predictor for the immune response in cancer patients, and could also represent a new potential immunotherapeutic target.

摘要

背景

结肠癌转移相关基因 1(MACC1)是转移的有效生物标志物,与生存相关。尽管大量实验证据表明 MACC1 与多种癌症相关,但尚未针对该标志物进行泛癌症分析,其在免疫学中的作用也尚不清楚。

材料和方法

在我们的研究中,我们使用多个数据库(包括 TIMER2、GEPIA2、Kaplan-Meier plotter)分析 MACC1 的表达及其对预后的影响。使用 UALCAN 数据库评估 MACC1 启动子甲基化水平。基于 TCGA 数据库,我们使用 R 编程语言探索 MACC1 与肿瘤突变负担(TMB)、微卫星不稳定性(MSI)、免疫检查点之间的关系。我们通过 TIMER 和 UALCAN 评估 MACC1 与免疫浸润的相关性。

结果

我们的结果表明,异常的 DNA 甲基化可能是导致癌症类型中 MACC1 表达不同的重要原因。同时,我们探讨了 MACC1 的潜在致癌作用,并发现其具有显著的预后价值。MACC1 可能与 T 细胞功能和肿瘤相关巨噬细胞的极化有关,尤其是在 STAD 和 LGG 中。其表达与免疫浸润有关,与免疫检查点相关基因密切相关,特别是 CD274 和 SIGLEC15,这表明 MACC1 可能是几种恶性肿瘤潜在的免疫治疗靶点。我们的论文首次揭示了 MACC1 与癌症免疫学之间的关系。

结论

MACC1 可能作为癌症患者免疫反应的预测因子,也可能代表一种新的潜在免疫治疗靶点。

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