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 Kumar Sharma, Robert Schleifer, Jin-Xiong She

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number581
JournalBMC Cancer
Volume19
Issue number1
DOIs
StatePublished - Jun 14 2019

Fingerprint

Metalloproteases
Transcriptome
Matrix Metalloproteinases
Neoplasms
Genes
Gene Expression
Atlases
Kidney Neoplasms
Survival Analysis
Renal Cell Carcinoma
ROC Curve
Area Under Curve
Cluster Analysis
Disease Progression

Keywords

  • Biomarkers
  • Diagnosis
  • Gene expression
  • MMPs
  • Matrix metalloproteases
  • Prognosis
  • Survival
  • TCGA

ASJC Scopus subject areas

  • Genetics
  • Oncology
  • Cancer Research

Cite this

A pan-cancer perspective of matrix metalloproteases (MMP) gene expression profile and their diagnostic/prognostic potential. / Gobin, Emily; Bagwell, Kayla; Wagner, John; Mysona, David; Sandirasegarane, Sharmila; Smith, Nathan; Bai, Shan; Sharma, Ashok Kumar; Schleifer, Robert; She, Jin-Xiong.

In: BMC Cancer, Vol. 19, No. 1, 581, 14.06.2019.

Research output: Contribution to journalArticle

Gobin, Emily ; Bagwell, Kayla ; Wagner, John ; Mysona, David ; Sandirasegarane, Sharmila ; Smith, Nathan ; Bai, Shan ; Sharma, Ashok Kumar ; Schleifer, Robert ; She, Jin-Xiong. / A pan-cancer perspective of matrix metalloproteases (MMP) gene expression profile and their diagnostic/prognostic potential. In: BMC Cancer. 2019 ; Vol. 19, No. 1.
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AU - Gobin, Emily

AU - Bagwell, Kayla

AU - Wagner, John

AU - Mysona, David

AU - Sandirasegarane, Sharmila

AU - Smith, Nathan

AU - Bai, Shan

AU - Sharma, Ashok Kumar

AU - Schleifer, Robert

AU - She, Jin-Xiong

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N2 - 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.

AB - 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.

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KW - Diagnosis

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KW - Prognosis

KW - Survival

KW - TCGA

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