M6A Modifier-Mediated Methylation Characterized by Diverse Prognosis, Tumor Microenvironment, and Immunotherapy Response in Hepatocellular Carcinoma

被引：4

作者：

Liu, Fei ^{[1
]}

Zhang, Xinyue ^{[2
]}

Liu, Ziyu ^{[3
]}

Cai, Weiye ^{[1
]}

Song, Chao ^{[1
]}

Jiang, Yan ^{[4
]}

Yin, Ji ^{[4
]}

Liu, Zongchao ^{[1
]}

Huang, Chenyi ^{[1
]}

机构：

[1] Southwest Med Univ, Affiliated Tradit Chinese Med Hosp, Dept Orthoped, Luzhou 646000, Sichuan, Peoples R China

[2] Southwest Med Univ, Affiliated Tradit Chinese Med Hosp, Coll Integrated Chinese & Western Med, Luzhou 646000, Sichuan, Peoples R China

[3] Southwest Med Univ, Affiliated Tradit Chinese Med Hosp, Ctr Phen Tradit Chinese Med, Luzhou 646000, Sichuan, Peoples R China

[4] Southwest Med Univ, Affiliated Tradit Chinese Med Hosp, Dept Otorhinolaryngol, Luzhou 646000, Sichuan, Peoples R China

来源：

JOURNAL OF ONCOLOGY | 2022年 / 2022卷

关键词：

DISCOVERY;

D O I：

10.1155/2022/2513813

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Objective. Emerging evidence highlights the clinical implications of N-6-methyladenosine (m(6)A) modification in HCC. Yet, the roles of m(6)A modification in modulating cancer immunity and shaping tumor microenvironment (TME) are undefined in hepatocellular carcinoma (HCC). Methods. Here, m(6)A modification classification was determined for HCC through 23 m(6)A modifier levels by employing consensus clustering approach. Prognosis analysis was presented for comparing the differences in survival outcomes. The ssGSEA and ESTIMATE approaches were adopted for evaluating the abundances of tumor-infiltrating immune cell populations. The m(6)A scoring system was computed for reflecting m(6)A modification classification via PCA algorithm. Results. Three m(6)A modifier-mediated modification patterns were established among HCC specimens, which were characterized by different prognosis, signaling pathways, and TME features. After extracting m(6)A phenotype-associated DEGs, we determined m(6)A scores in individual HCC and stratified patients into high- and low-score groups. Patients with low m6A score displayed the survival advantage and higher sensitivity to gemcitabine. Moreover, those with low m(6)A score possessed the better anti-PD-1/PD-L1 therapeutic response in the IMvigor210 immunotherapy cohort. Conclusion. Our findings highlighted that m(6)A modification exerted a nonnegligible role in remodeling diverse and complex TME. Quantification of the m(6)A modification patterns of individual HCC may enhance the comprehension of TME features and facilitate immunotherapeutic plans.

引用

页数：25