Age-Associated Proteomic Signatures and Potential Clinically Actionable Targets of Colorectal Cancer

The occurrence and prevalence of colorectal cancer (CRC) is closely associated with age. More than 90% of patients with CRC are diagnosed after 50 years of age. However, CRC incidence of young individuals has been increasing since 1990s, whereas the overall CRC frequency is declining. Distinct overall survival rates between young and aged patients with CRC have been established. Tremendous efforts have been made to clarify the underlying mechanisms of age-dependent clinical differences, but it still remains elusive. Here, we performed proteomic profiling of 50 patients with CRC and revealed proteomic signatures of CRC across age groups. Gene set enrichment analysis showed that distinct age-dependent clinical outcomes might mainly attribute to varied MYC targets V1/V2, E2F targets and G2M checkpoint gene sets, which were associated with cancer cell proliferation, cell apoptosis, tumor growth, and tumor metastasis. Multiple linear regression analysis revealed a large number of functional proteins, such as NOP2, CSE1L, NHP2, NOC2L and CDK1, with adjusted expression significantly correlated with age (p < 0.05). Among them, NHP2 is a core component of the telomerase complex associated with age. High NHP2 expression predicted poor overall survival, with a more significant correlation in aged patients with CRC. Knockdown of NHP2 significantly suppressed cancer cell proliferation. In addition, we revealed some age-related potential clinically actionable targets, such as PSEN1, TSPO, and CDK1, which might be more suitable for patients with late-onset CRC. Collectively, this study identifies age-associated proteomic signatures and potential therapeutic targets of CRC and may help make a precise decision on CRC treatment. [Display omitted] •The proteomic signatures of early-onset CRC are disclosed.•Alterations of some proteins between cancerous and normal tissues are age-correlated.•NHP2, overexpressed in tumors especially in aged patients, predicts poor prognosis.•Potential age-dependent druggable targets and their inhibitors are summarized. The incidence of early-onset colorectal cancer (CRC) has been increasing since 1990s, whereas the overall CRC frequency is declining. The underlying mechanisms of age-related clinical differences remain unknown. Here, we reported the proteomic signatures of CRC across age groups. Lots of proteins with adjusted intensities significantly correlated with age. Some proteins were verified as potential clinically actionable targets. T