Cancer-associated fibroblasts in early-stage lung adenocarcinoma correlate with tumor aggressiveness

被引:2
|
作者
Vasiukov, Georgii [1 ]
Zou, Yong [2 ]
Senosain, Maria-Fernanda [2 ]
Rahman, Jamshedur S. M. [2 ]
Antic, Sanja [2 ]
Young, Katherine M. [1 ]
Grogan, Eric L. [3 ]
Kammer, Michael N. [2 ]
Maldonado, Fabien [2 ]
Reinhart-King, Cynthia A. [1 ]
Massion, Pierre P. [2 ]
机构
[1] Vanderbilt Univ, Dept Biomed Engn, Sch Engn, Nashville, TN 37235 USA
[2] Vanderbilt Univ, Div Pulm & Crit Care Med, Med Ctr, Nashville, TN USA
[3] Vanderbilt Univ, Div Thorac Surg, Med Ctr, Nashville, TN USA
关键词
DIFFERENTIAL EXPRESSION ANALYSIS; PROLIFERATION; DECORIN;
D O I
10.1038/s41598-023-43296-3
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
Lung adenocarcinoma (LUAD) is the predominant type of lung cancer in the U.S. and exhibits a broad variety of behaviors ranging from indolent to aggressive. Identification of the biological determinants of LUAD behavior at early stages can improve existing diagnostic and treatment strategies. Extracellular matrix (ECM) remodeling and cancer-associated fibroblasts play a crucial role in the regulation of cancer aggressiveness and there is a growing need to investigate their role in the determination of LUAD behavior at early stages. We analyzed tissue samples isolated from patients with LUAD at early stages and used imaging-based biomarkers to predict LUAD behavior. Single-cell RNA sequencing and histological assessment showed that aggressive LUADs are characterized by a decreased number of ADH1B(+) CAFs in comparison to indolent tumors. ADH1B(+) CAF enrichment is associated with distinct ECM and immune cell signatures in early-stage LUADs. Also, we found a positive correlation between the gene expression of ADH1B(+) CAF markers in early-stage LUADs and better survival. We performed TCGA dataset analysis to validate our findings. Identified associations can be used for the development of the predictive model of LUAD aggressiveness and novel therapeutic approaches.
引用
收藏
页数:13
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