Abstract

Background Colorectal cancer (CRC) is the second most common cause of cancer death in the United States and the third most common cancer globally. The incidence of CRC tends to be younger, and we urgently need a reliable prognostic assessment strategy. Methods Protein expression profile and clinical information of 390 CRC patients/samples were downloaded from the TCPA and TCGA database, respectively. The Kaplan-Meier, Cox regression, and Pearson correlation analysis were applied in this study. Results Based on the TCPA and TCGA database, we screened 6 hub proteins and first constructed protein risk signature, all of which were significantly associated with CRC patients' overall survival (OS). The risk score was an independent prognostic factor and significantly related with the size of the tumor in situ (T). 6 hub proteins were differentially expressed in cancer and normal tissues and in different CRC stages, which were validated at the ONCOMINE database. Next, 40 coexpressed proteins of 6 hub proteins were extracted from the TCPA database. In the protein-protein interaction (PPI) network, HER1, HER2, and CTNNB1 were at the center. Function enrichment analysis illustrated that 46 proteins were mainly involved in the EGFR (HER1) tyrosine kinase inhibitor resistance pathway. Conclusion Studies indicated that 6 hub proteins might be considered as new targets for CRC therapies, and the protein risk signature can be used to predict the OS of CRC patients.

Highlights

  • According to the 2020 Colorectal Cancer Statistics, colorectal cancer (CRC) is the second most common cancer death in the United States [1]

  • With the help of the UALCAN website, we further found that 6 hub proteins were differentially expressed in cancer and normal tissues and in different CRC stages, which were validated at the ONCOMINE database

  • In order to mine the molecular characteristics of 6 hub proteins, we performed protein-protein interaction (PPI) and enrichment analysis based on the 6 hub proteins and their coexpressed proteins. We found that these proteins were mainly enriched in EGFR (HER1) tyrosine kinase inhibitor resistance, regulation of DNA metabolic process, and pathways in cancers, all of which were directly associated with tumorigenesis

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Summary

Introduction

According to the 2020 Colorectal Cancer Statistics, colorectal cancer (CRC) is the second most common cancer death in the United States [1]. Protein risk signature has never been constructed to predict the prognosis of CRC patients. Protein expression profile and clinical information of 390 CRC patients/samples were downloaded from the TCPA and TCGA database, respectively. Based on the TCPA and TCGA database, we screened 6 hub proteins and first constructed protein risk signature, all of which were significantly associated with CRC patients’ overall survival (OS). 6 hub proteins were differentially expressed in cancer and normal tissues and in different CRC stages, which were validated at the ONCOMINE database. Studies indicated that 6 hub proteins might be considered as new targets for CRC therapies, and the protein risk signature can be used to predict the OS of CRC patients

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