A pan-cancer perspective of matrix metalloproteases (MMP) gene expression profile and their diagnostic/prognostic potential

Emily Gobin†,
Kayla Bagwell†,
John Wagner†,
David Mysona,
Sharmila Sandirasegarane,
Nathan Smith,
Shan Bai,
Ashok Sharma,
Robert Schleifer and
Jin-Xiong SheEmail author

†Contributed equally

BMC Cancer201919:581

https://doi.org/10.1186/s12885-019-5768-0

Received: 6 September 2018
Accepted: 29 May 2019
Published: 14 June 2019

Open Peer Review reports

Abstract

Implication

By understanding Matrix Metalloprotease (MMP) dysregulation from a pan-cancer perspective, this study sheds light on the diagnostic potentials of MMPs across multiple neoplasms.

Background

MMPs are intriguing genes related to cancer disease progression, functional promotion of angiogenesis, invasion, metastasis, and avoidance of immune surveillance. Many studies have noted these genes are frequently upregulated in cancer. However, expression patterns of all MMPs and their diagnostic and prognostic potential have not been investigated in a pan-cancer perspective.

Methods

The Cancer Genome Atlas (TCGA) data were used to evaluate diagnostic and prognostic potential of 24 MMPs in fifteen different cancer types. Gene expression measured by RNA-seq was analyzed by differential expression, hierarchical clustering, and ROC analysis for individual genes and in combination.

Results

MMP1, MMP9, MMP10, MMP11, and MMP13 were almost universally upregulated across all cancers, with significant (p < 0.05) fold change (FC > 2) in ten of fifteen cancers. MMP3, MMP7, MMP12 and MMP14) are significantly up-regulated in at least 10 cancer types. Interestingly, MMP2, MMP7, MMP23B, MMP27 and MMP28) are significantly down-regulated in seven to nine cancer types. Multiple MMPs possess AUC’s > 0.9 in more than one cancer. However, survival analyses suggest that the prognostic value of MMPs is limited to clear cell renal carcinoma.

Conclusions

Most MMPs have consistently increased gene expression across cancers, while several MMPs have consistently decreased expression in several cancer types. Many MMPs have diagnostic value individually or in combination, while the prognostic value of MMPs is restricted to one subtype of kidney cancer.