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Research Paper|Volume 12, Issue 18|pp 18676—18692

Identification of genomic alterations and associated transcriptomic profiling reveal the prognostic significance of MMP14 and PKM2 in patients with pancreatic cancer

Haiwei Wang1,2, Xinrui Wang1,2, Liangpu Xu1,2, Yingying Lin3, Ji Zhang4, Hua Cao1,2
  • 1Medical Research Center, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
  • 2Key Laboratory of Technical Evaluation of Fertility Regulation for Non-human Primate, National Health and Family Planning Commission, Fuzhou, Fujian, China
  • 3Department of Neurosurgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • 4State Key Laboratory for Medical Genomics, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
* Equal contribution
Received: April 6, 2020Accepted: July 30, 2020Published: September 17, 2020
https://doi.org/10.18632/aging.103958

Copyright: © 2020 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Pancreatic cancer is characterized by multiple genomic alterations, including KRAS mutations, TP53 mutations and CDKN2A deletion. However, the prognostic relevance of those genomic alterations and associated transcriptomic profiling in pancreatic cancer are unclear. Integrated analysis of The Cancer Genome Atlas (TCGA) datasets revealed that KRAS mutation, TP53 mutation and CDKN2A deletion were all bad prognostic factors in pancreatic cancer. And KRAS mutation, TP53 mutation and CDKN2A deletion were coordinated and co-occurred in pancreatic cancer. Transcriptomic analysis showed that MMP14 and PKM2 were both up-regulated by KRAS mutation, TP53 mutation or CDKN2A deletion. Also, MMP14 and PKM2 were both associated with unfavorable outcomes in pancreatic cancer. Compared with normal tissues, MMP14 and PKM2 were up-regulated in pancreatic cancer tissues. 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.