Proteomic profiling of IgA nephropathy reveals distinct molecular prognostic subtypes

被引：12

作者：

Chen, Xizhao ^{[1
]}

Li, Mansheng ^{[2
]}

Zhu, Songbiao ^{[3
]}

Lu, Yang ^{[1
]}

Duan, Shuwei ^{[1
]}

Wang, Xu ^{[1
]}

Wang, Yong ^{[1
]}

Chen, Pu ^{[4
]}

Wu, Jie ^{[1
]}

Wu, Di ^{[4
]}

Feng, Zhe ^{[1
]}

Cai, Guangyan ^{[1
]}

Zhu, Yunping ^{[2
]}

Deng, Haiteng ^{[3
]}

Chen, Xiangmei ^{[1
]}

机构：

[1] Chinese Peoples Liberat Army Gen Hosp, Chinese Peoples Liberat Army, Natl Clin Res Ctr Kidney Dis, State Key Lab Kidney Dis,Dept Nephrol,Med Ctr 1,Ne, Beijing 100853, Peoples R China

[2] Beijing Proteome Res Ctr, Beijing Inst Life Omics, Natl Ctr Prot Sci Beijing, State Key Lab Prote, Beijing 102206, Peoples R China

[3] Tsinghua Univ, Ctr Synthet & Systemat Biol, Sch Life Sci, MOE Key Lab Bioinformat, Beijing 100084, Peoples R China

[4] Capital Med Univ, Dept Nephrol, Elect Power Teaching Hosp, Beijing 100073, Peoples R China

来源：

ISCIENCE | 2023年 / 26卷 / 03期

关键词：

PATHOGENESIS; MITOCHONDRIA; COMPLEMENT; METABOLISM; INSIGHTS; SCORE;

D O I：

10.1016/j.isci.2023.105961

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

IgA nephropathy (IgAN) is a heterogeneous disease, which poses a series of lenges to accurate diagnosis and personalized therapy. Herein, we constructed systematic quantitative proteome atlas from 59 IgAN and 19 normal control nors. Consensus sub-clustering of proteomic profiles divided IgAN into three types (IgAN-C1, C2, and C3). IgAN-C2 had similar proteome expression patterns with normal control, while IgAN-C1/C3 exhibited higher level of complement vation, more severe mitochondrial injury, and significant extracellular accumulation. Interestingly, the complement mitochondrial extracellular (CME) pathway enrichment score achieved a high diagnostic power to distinguish IgAN-C2 from IgAN-C1/C3 (AUC>0.9). In addition, the proteins related to gial cells, endothelial cells, and tubular interstitial fibrosis were highly expressed in IgAN-C1/C3. Most critically, IgAN-C1/C3 had a worse prognosis compared IgAN-C2 (30% eGFR decline, p = 0.02). Altogether, we proposed a molecular typing and prognostic system which could help to understand IgAN heterogene-ity and improve the treatment in the clinic.

引用

页数：17

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