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Simple Summary: Colorectal cancer (CRC) is one of the most common cancers, which has a poor prognosis and is prone to recurrence and metastasis. DPP7 is a prolyl peptidase, which is an enzyme characterized by the feature of cleaving proline-containing peptides. We found that the expression level of DPP7 in CRC samples was significantly higher than that in adjacent non-tumor tissues by analyzing public colorectal cancer data and surgical specimens of CRC patients. Moreover, the increased expression of DPP7 is correlated with a higher stage of cancer and shorter overall survival, indicating the diagnostic value of DPP7 for CRC. Furthermore, functional annotations indicated that DPP7 is involved in neuroactive ligand–receptor interaction and olfactory transduction signaling. Our data demonstrated that DPP7 is a promising diagnostic and prognostic biomarker as well as a new therapeutic target for CRC. Colorectal cancer has a poor prognosis and is prone to recurrence and metastasis. DPP7, a prolyl peptidase, is reported to regulate lymphocyte quiescence. However, the correlation of DPP7 with prognosis in CRC remains unclear. With publicly available cohorts, the Wilcoxon rank-sum test and logistic regression were employed to analyze the relationship between DPP7 expression and the clinicopathological features of CRC patients. Specific pathways of differentially expressed genes were determined through biofunctional analysis and gene set enrichment analysis (GSEA). qPCR and immunohistochemical staining were used to determine DPP7 expression levels in surgical specimens. The public dataset and analysis of the biospecimens of CRC patients revealed that DPP7, in the CRC samples, was expressed significantly higher than in non-tumor tissues. Moreover, increased DPP7 was significantly associated with a higher N stage, lymphatic invasion, and shorter overall survival. Functionally, DPP7 is involved in neuroactive ligand–receptor interaction and olfactory transduction signaling. We identified a series of targeted drugs and small-molecule drugs with responses to DPP7. To conclude, DPP7 is a valuable diagnostic and prognostic biomarker for CRC and considered as a new therapeutic target. [ABSTRACT FROM AUTHOR]

• Highly expressed CXCL1-3, 5, 8 exert an important effect on CRC oncogenesis. • Highly expressed CXCL10-11 serve as positive prognostic factors for CRC patients. • CXCL9-11 may recruit anti-tumor CD8+ T cells and NK cells in CRC patients. The C-X-C motif (CXC) chemokines play an important role in inflammatory processes and angiogenesis and are also associated with tumor development, progression and metastasis. They can be either promoting or inhibiting factors in colorectal cancers (CRC). The expression patterns and prognostic values of the CXC family still need further investigation. In this study, we investigated data related to transcription, translation, survival and tumor immune infiltration for CXC chemokines in patients with CRC from the ONCOMINE, GEPIA, cBioPortal, HPA and TIMER databases. We found that the expression levels of CXCL1-3, CXCL5, and CXCL8 were higher in CRC tissues than in colorectal tissues. Expression among stages significantly varied for CXCL1-3 and CXCL9-11. The survival analysis revealed that high transcriptional levels of CXCL4 and CXCL9-11 could serve as positive prognostic factors for patients with CRC. CXCL9-11 were highly associated with CD8+ T cells and natural killer (NK) cells in the tumor immune infiltration analysis, indicating their role in the antitumor immune response. This study implies that CXCL1-3, CXCL5, and CXCL8 are important factors during CRC oncogenesis and that CXCL9-11 could be new biomarkers for the prognosis of CRC. [ABSTRACT FROM AUTHOR]