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Aging-US: The prognostic significance of MMP14 and PKM2 in patients with pancreatic cancer

11-16-2020

Aging-US recently published "Identification of genomic alterations and associated transcriptomic profiling reveal the prognostic significance of MMP14 and PKM2 in patients with pancreatic cancer" which reported that Integrated analysis of The Cancer Genome Atlas datasets revealed that KRAS mutation, TP53 mutation and CDKN2A deletion were all bad prognostic factors in pancreatic cancer.

Moreover, MMP14 and PKM2 were highly expressed in high grade of pancreatic cancer.

Furthermore, MMP14 and PKM2 were correlated with each other, and the combination of MMP14 and PKM2 could be used as better prognostic markers than MMP14 or PKM2 alone.

At last, the high expression and bad prognostic effects of MMP14 and PKM2 in pancreatic cancer were validated using tissue microarray.

Overall, the genomic alterations and associated transcriptomic profiling analysis suggested new prognostic makers of MMP14 and PKM2 in pancreatic cancer.

"The genomic alterations and associated transcriptomic profiling analysis suggested new prognostic makers of MMP14 and PKM2 in pancreatic cancer"

Dr. Haiwei Wang and Dr. Hua Cao both from The Affiliated Hospital of Fujian Medical University as well as The National Health and Family Planning Commission & Dr. Ji Zhang from The Shanghai Jiao Tong University School of Medicine said, "Pancreatic cancer is a highly aggressive disease and one of leading cause of cancer related mortality."

The first whole-exome sequencing study suggests that pancreatic cancer is characterized by KRAS mutation, TP53 mutation, CDKN2A deletion and SMAD alteration .

KRAS mutation also cooperates with TP53 mutation or SMAD4 alteration to promote the metastasis of pancreatic cancer.

Moreover, pancreatic cancer patients with KRAS mutation, TP53 mutation, CDKN2A deletion and SMAD alteration tend to have worse clinical outcomes .

So, the synergism of KRAS mutation, TP53 mutation, CDKN2A deletion and SMAD alteration in the prognosis of pancreatic cancer still need to be illustrated.

Figure 9. Validation of the expression and prognostic significance of MMP14 and PKM2 in pancreatic cancer by tissue microarray. (A) Representative photographs of immunohistochemical features of the stained sections of MMP14 and PKM2 in pancreatic cancer tissues and adjacent normal tissues. (B) Kaplan-Meier survival analysis was used to determine the different overall survival of pancreatic cancer patients with highly stained MMP14 or PKM2 (red) and pancreatic cancer patients with low stained MMP14 or PKM2 (blue). P values were generated from Log-rank test. (C) Contingency graphs showed the number of pancreatic cancer patients with both high MMP14 and PKM2 expression. P values were determined by Chi-square test. (D) Kaplan-Meier plotters demonstrated the different overall survival of pancreatic cancer patients with different expression levels of MMP14 and PKM2.

In the present study, using large cohorts of pancreatic cancer patients derived from TCGA datasets and Gene Expression Omnibus datasets, the prognostic significance of KRAS mutation, TP53 mutation, CDKN2A deletion and SMAD alteration was determined.

The Wang/Cao/Zhang Research Team concluded in their Aging-US Research Paper that overall, by integrated analysis of TCGA and GEO datasets, their results provide deep understandings of how the KRAS, TP53, CDKN2A and SMAD4 genetic alterations and their related genes influence the clinical overall survival of pancreatic cancer patients.

The authors results also suggest new prognostic markers of MMP14 and PKM2 in pancreatic cancer.

Furthermore, the prognostic effects of MMP14 and PKM2 are validated in Chinese pancreatic cancer patients.

Although, the functions and correlations of MMP14 and PKM2 in pancreatic cancer patients require further elucidation, the combination of MMP14 and PKM2 could be used as better biomarkers to predict the overall survival of pancreatic cancer patients.

Full Text - https://doi.org/10.18632/aging.103958

Correspondence to: Haiwei Wang email: hwwang@sibs.ac.cn, Hua Cao email: caohua69@fjmu.edu.cn, and Ji Zhang email: Zj11222@rjh.com.cn

Keywords: pancreatic cancer, KRAS mutation, TP53 mutation, CDKN2A deletion, MMP14

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The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population.

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