Abstract
Background: Colorectal cancer (CRC) ranks among the leading causes of cancerrelated deaths.
Objective: This study aimed to illuminate the relationship between DPP7 (also known as DPP2) and CRC through a combination of bioinformatics and experimental methodologies.
Methods: A multi-dimensional bioinformatic analysis on DPP7 was executed, covering its expression, survival implications, clinical associations, functional roles, immune interactions, and drug sensitivities. Experimental validations involved siRNA-mediated DPP7 knockdown and various cellular assays.
Results: Data from the Cancer Genome Atlas (TCGA) identified high DPP7 expression in solid CRC tumors, with elevated levels adversely affecting patient prognosis. A shift from the N0 to the N2 stage in CRC was associated with increased DPP7 expression. Functional insights indicated the involvement of DPP7 in cancer progression, particularly in extracellular matrix disassembly. Immunological analyses showed its association with immunosuppressive entities, and in vitro experiments in CRC cell lines underscored its oncogenic attributes.
Conclusion: DPP7 could serve as a CRC prognosis marker, functioning as an oncogene and representing a potential immunotherapeutic target.
Graphical Abstract
[http://dx.doi.org/10.1002/path.5073] [PMID: 29537081]
[http://dx.doi.org/10.1016/S0959-8049(00)00015-0] [PMID: 10785591]
[http://dx.doi.org/10.1038/ncomms12499] [PMID: 27530650]
[http://dx.doi.org/10.3389/fimmu.2015.00387] [PMID: 26300881]
[http://dx.doi.org/10.3390/cancers13143588] [PMID: 34298800]
[http://dx.doi.org/10.3389/fonc.2020.00405] [PMID: 32296640]
[http://dx.doi.org/10.1038/ni.3201]
[http://dx.doi.org/10.3389/fimmu.2022.830863] [PMID: 35309368]
[http://dx.doi.org/10.1111/cei.12781] [PMID: 26919392]
[http://dx.doi.org/10.1038/ni.3210] [PMID: 26194276]
[http://dx.doi.org/10.1111/cei.12757] [PMID: 26671446]
[http://dx.doi.org/10.1002/dmrr.2530] [PMID: 24446278]
[http://dx.doi.org/10.1016/j.cca.2007.01.024] [PMID: 17328877]
[http://dx.doi.org/10.1016/j.exphem.2010.08.008] [PMID: 20817072]
[http://dx.doi.org/10.4049/jimmunol.163.6.3092] [PMID: 10477574]
[http://dx.doi.org/10.1002/eji.201041157] [PMID: 21469121]
[http://dx.doi.org/10.1016/j.intimp.2022.109608] [PMID: 36700778]
[http://dx.doi.org/10.1016/j.trim.2023.101860] [PMID: 37230395]
[PMID: 35559414]
[http://dx.doi.org/10.1371/journal.pone.0107468] [PMID: 25229481]
[http://dx.doi.org/10.1186/s12967-023-04029-2] [PMID: 36879254]
[http://dx.doi.org/10.1016/j.lfs.2023.121659] [PMID: 37011878]
[http://dx.doi.org/10.3389/fmolb.2020.584053] [PMID: 33195430]
[http://dx.doi.org/10.1016/j.dnarep.2020.103025] [PMID: 33248388]
[http://dx.doi.org/10.1016/j.jbc.2022.102374] [PMID: 35970393]
[http://dx.doi.org/10.1016/j.bbrc.2019.10.108] [PMID: 31640855]
[http://dx.doi.org/10.1038/sj.leu.2404247] [PMID: 16673019]
[http://dx.doi.org/10.3390/cancers11060836] [PMID: 31213005]
[http://dx.doi.org/10.1038/s41571-021-00549-2] [PMID: 34508258]
[PMID: 32266087]
[http://dx.doi.org/10.1016/j.diabres.2010.02.017] [PMID: 20303610]
[http://dx.doi.org/10.1111/j.1742-4658.2009.07526.x] [PMID: 20074209]
[http://dx.doi.org/10.1111/j.1471-4159.1989.tb01877.x] [PMID: 2564425]
[http://dx.doi.org/10.1016/j.biocel.2008.02.022] [PMID: 18396440]
b) Maes, B.; Lambeir, A.M.; Van der Veken, P.; De Winter, B.; Augustyns, K.; Scharpe, S.; Meester, I. De;, In vivo effects of a potent, selective DPPII inhibitor: UAMC00039 is a possible tool for the elucidation of the physiological function of DPPII. Adv. Exp. Med. Biol., 2006, 575, 73-85.;
c) Maes, B.; Lambeir, A.M.; Van der Veken, P.; De Winter, B.; Augustyns, K.; Scharpe, S.; Meester, I. De Kinetic investigation of human dipeptidyl peptidase II (DPPII)-mediated hydrolysis of dipeptide derivatives and its identification as quiescent cell proline dipeptidase (QPP)/dipeptidyl peptidase 7 (DPP7). Biochem. J., 2005, 386(pt 2), 315-324.
[http://dx.doi.org/10.1016/j.bbamcr.2022.119212] [PMID: 35090967]
[http://dx.doi.org/10.1101/gad.1624008] [PMID: 18381890]
[http://dx.doi.org/10.1038/s41420-022-00868-y] [PMID: 35210431]
[http://dx.doi.org/10.1016/j.yjmcc.2020.09.008] [PMID: 32971071]
[http://dx.doi.org/10.1111/cas.14069] [PMID: 31102428]
[http://dx.doi.org/10.1172/jci.insight.154646] [PMID: 35192548]
[http://dx.doi.org/10.1158/0008-5472.CAN-10-2460] [PMID: 20884631]
[http://dx.doi.org/10.1016/j.canlet.2020.10.032] [PMID: 33132120]
[http://dx.doi.org/10.1097/FJC.0000000000000453] [PMID: 28009720]
[http://dx.doi.org/10.1165/rcmb.2021-0406OC] [PMID: 35081328]
[http://dx.doi.org/10.3390/cells10010104] [PMID: 33429982]
[http://dx.doi.org/10.3748/wjg.14.5162] [PMID: 18777593]
[http://dx.doi.org/10.1371/journal.pone.0166233] [PMID: 27898692]