Immunothérapie : Libre accès
Libre accès

Abstrait

A Perspective of Matrix Metalloproteases (MMP) Gene Expression Profile Revealed by Pan-cancer Transcriptome and Single Cell Data

Jinxiang Tan*, Yidan Gao, Zhao Li, Yuanyuan Wang, Linbang Wang

Background: MMPs are a group of family genes that related to cancer progression, up regulation of most of the MMP genes in cancers are reported to be associated with promotion of invasion, angiogenesis, and immune surveillance avoidance. However, expression patterns of all MMPs in transcriptome level and single-cell level in a pan-cancer perspective have not been investigated.

Methods: Both the Cancer Genome Atlas (TCGA) transcriptome and single-cell sequencing pan-cancer data from GEO (Gene Expression Omnibus) were applied. The MMP-based diagnostic model was constructed by LASSO regression analysis. Tumors were classified into MMP score-high and low groups by ssGSEA. Single-cell data was analysisd by Serat package. The expression characters of MMPs were validated by qRT-PCR.

Results: MMP1, MMP11, and MMP12 were up regulated across almost all cancers. MMP19 and MMP27 are significantly down-regulated in eight to nine cancer types. Correlation analysis proved a potential relation between MMP expression and tumor immune and tumor stemness. Immune cells including Macrophages, Type II IFN Reponse, and Treg were highly infiltrated in MMP score-low group as expected, functions including Hippo signaling pathway, positive regulation of leukocyte adhesion to vascular endothelial cell, T cell chemo taxis more active in MMP score-high group. Single-cell analysis revealed diverse MMP expressions pattern in different cell clusters. In which, MMP7 are found to be highly expressed in the macrophages and MMP2 are found to be highly expressed in the CD8⁺T cells.

Conclusion: Majority of MMPs has increased expression across cancers, MMPs showed potential diagnostic value in combination.