Abstract
To clarify the molecular mechanisms underlying the poor prognosis of right-sided and mucinous colon cancer at the proteomic level. A tandem mass tag-proteomics approach was used to identify differentially expressed proteins (DEPs) in colon carcinoma tissues from different locations and with different histological types to reveal the underlying mechanisms of these differences at the protein level. In additional, the DEPs were analyzed using bioinformatics methods. The proteomics profiles among colon cancers with different tumor locations and histological types were dramatically distinguished. In terms of tumor locations, the right-sided carcinoma specific DEPs may promote the tumor progression via activating inflammation, metastasis associated pathways. When referring to histological types, the mucinous colon cancers perhaps increased the invasion and metastasis through distinct mechanisms in different tumor locations. For mucinous cancer located in right-sided colon, the mucinous specific DEPs were mainly associated with ECM-related remodeling and the IL-17 signal pathway. For mucinous cancer located in left-sided colon, the mucinous specific DEPs showed a strong relationship with ACE2/Ang-(1–7)/MasR axis. The proteomics profiles of colon cancers showed distinct differences related to locations and histological types. These results suggested a distinct mechanism underlying the diverse subtypes of colon cancers.
Highlights
Colorectal cancer (CRC) is the second leading cause of cancer-related death and the fourth most frequently diagnosed cancer worldwide [1]
Group; cancer tissues from six patients with left-sided mucinous colon cancer were included in the LMC group; cancer tissues from eight patients with left-sided non-mucinous colon cancer were included in the LNMC group; cancer tissues from seven patients with rightsided mucinous colon cancer were included in the RMC group; and cancer tissues from eight patients with right-sided mucinous colon cancer were included in the right-sided non-mucinous colon cancer (RNMC) group
LMC, RMC and RNMC, LMC and LNMC, to obtain a comprehensive description of colon cancer differentially expressed proteins (DEPs) associated with different sites and histological types
Summary
Colorectal cancer (CRC) is the second leading cause of cancer-related death and the fourth most frequently diagnosed cancer worldwide [1]. With improvements in precise and individualized treatments, there is a pressing requirement for the refinement of the classification of CRC subtypes based on their tumor locations and histological characteristics. According to the location of the primary tumor, CRC can be divided into left-sided. A retrospective analysis showed that the location of the primary tumor can be used to predict the treatment outcome and metastasis of colon cancer [2]. The prognosis of right-sided tumors was found to be worse than that of left-sided tumor [7]. In another retrospective study of 4034 patients with stage III colon cancer, patients with right-sided tumors had shorter overall survival than those with left-sided tumors [8].
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