Login Register Cart 0
Generic placeholder image

Current Cancer Drug Targets

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Pan-cancer Analysis Confirms the Prognostic and Immunological Effects of Prostate Tumor Overexpressed-1 in Human Cancers

Author(s): Fashun Liu, Songlin Wan, Yue Li, Zhenxiong Ye, Daojiang Li and Zhen Li*

Volume 24, Issue 1, 2024

Published on: 19 April, 2023

Page: [28 - 45] Pages: 18

DOI: 10.2174/1568009623666230316153813

Price: $65

conference banner
Abstract

Background: Prostate tumor overexpressed-1 (PTOV1) is a conserved oncogenic adaptor protein associated with cancer progression and may be an independent prognostic marker for several malignancies. Consequently, using pan-cancer research to explore the significance of PTOV1 is valuable, and may reveal novel targets for cancer treatment.

Methods: A comprehensive bioinformatics analysis of PTOV1 was performed. The qRT-PCR was utilized to confirm the aberrant PTOV1 expression in several cancer cell lines.

Results: We observed that PTOV1 mRNA expression was high in 18 cancer tissues and was thereafter associated with poor survival prognosis in a range of malignancies. The immune subtypes of 14 malignancies and the molecular subtypes of six malignancies were related to PTOV1. A substantial association between PTOV1 and immune checkpoint (ICP) genes was also observed. Tumor mutational burden (TMB), microsatellite instability (MSI), and DNA methylation analyses indicated that PTOV1 acts as a cancer-promoting agent in a series of tumors. In addition, an enrichment study of PTOV1 and related genes revealed that RNA splicing may be responsible for the involvement of PTOV1 in cancers. Lastly, we also verified that PTOV1 expression was elevated in bladder cancer, breast cancer, CESC, LIHC cell lines via qRT-PCR.

Conclusion: Our bioinformatics research indicated that PTOV1 may be involved in tumor immunity. Furthermore, differentially expressed PTOV1 was found to be related to poor prognosis in cancers, and RNA splicing may be the specific mechanism for this effect. Therefore, PTOV1 mRNA and the corresponding protein may function as potential prognostic indicators and therapeutic targets in various cancers.

« Previous Next »
Graphical Abstract

[1]
Benedit, P.; Paciucci, R.; Thomson, T.M.; Valeri, M.; Nadal, M.; Càceres, C.; de Torres, I.; Estivill, X.; Lozano, J.J.; Morote, J.; Reventós, J. PTOV1, a novel protein overexpressed in prostate cancer containing a new class of protein homology blocks. Oncogene, 2001, 20(12), 1455-1464.
[http://dx.doi.org/10.1038/sj.onc.1204233] [PMID: 11313889]
[2]
Santamaría, A.; Fernández, P.L.; Farré, X.; Benedit, P.; Reventós, J.; Morote, J.; Paciucci, R.; Thomson, T.M. PTOV-1, a novel protein overexpressed in prostate cancer, shuttles between the cytoplasm and the nucleus and promotes entry into the S phase of the cell division cycle. Am. J. Pathol., 2003, 162(3), 897-905.
[http://dx.doi.org/10.1016/S0002-9440(10)63885-0] [PMID: 12598323]
[3]
Cánovas, V.; Lleonart, M.; Morote, J.; Paciucci, R. The role of prostate tumor overexpressed 1 in cancer progression. Oncotarget, 2017, 8(7), 12451-12471.
[http://dx.doi.org/10.18632/oncotarget.14104] [PMID: 28029646]
[4]
Youn, H.S.; Park, U.H.; Kim, E.J.; Um, S.J. PTOV1 antagonizes MED25 in RAR transcriptional activation. Biochem. Biophys. Res. Commun., 2011, 404(1), 239-244.
[http://dx.doi.org/10.1016/j.bbrc.2010.11.100] [PMID: 21110951]
[5]
Shilkaitis, A.; Green, A.; Christov, K. Retinoids induce cellular senescence in breast cancer cells by RAR-β dependent and independent pathways: Potential clinical implications. (Review). Int. J. Oncol., 2015, 47(1), 35-42.
[http://dx.doi.org/10.3892/ijo.2015.3013] [PMID: 25997921]
[6]
Artavanis-Tsakonas, S.; Rand, M.D.; Lake, R.J. Notch signaling: Cell fate control and signal integration in development. Science, 1999, 284(5415), 770-776.
[http://dx.doi.org/10.1126/science.284.5415.770] [PMID: 10221902]
[7]
Kolev, V.; Mandinova, A.; Guinea-Viniegra, J.; Hu, B.; Lefort, K.; Lambertini, C.; Neel, V.; Dummer, R.; Wagner, E.F.; Dotto, G.P. EGFR signalling as a negative regulator of Notch1 gene transcription and function in proliferating keratinocytes and cancer. Nat. Cell Biol., 2008, 10(8), 902-911.
[http://dx.doi.org/10.1038/ncb1750] [PMID: 18604200]
[8]
Alaña, L.; Sesé, M.; Cánovas, V.; Punyal, Y.; Fernández, Y.; Abasolo, I.; de Torres, I.; Ruiz, C.; Espinosa, L.; Bigas, A.; y Cajal, S.R.; Fernández, P.L.; Serras, F.; Corominas, M.; Thomson, T.M.; Paciucci, R. Prostate tumor OVerexpressed-1 (PTOV1) down-regulates HES1 and HEY1 notch targets genes and promotes prostate cancer progression. Mol. Cancer, 2014, 13(1), 74.
[http://dx.doi.org/10.1186/1476-4598-13-74] [PMID: 24684754]
[9]
Li, R.; Leng, A.; Liu, X.; Hu, T.; Zhang, L.; Li, M.; Jiang, X.; Zhou, Y.; Xu, C. Overexpressed PTOV1 associates with tumorigenesis and progression of esophageal squamous cell carcinoma. Tumour Biol., 2017, 39(6), 1-10.
[http://dx.doi.org/10.1177/1010428317705013] [PMID: 28651486]
[10]
Guo, F.; Feng, L.; Hu, J.L.; Wang, M.L.; Luo, P.; Zhong, X.M.; Deng, A.M. Increased PTOV1 expression is related to poor prognosis in epithelial ovarian cancer. Tumour Biol., 2015, 36(1), 453-458.
[http://dx.doi.org/10.1007/s13277-014-2662-x] [PMID: 25270739]
[11]
Yang, Q.; Lin, H.; Wu, S.; Lei, F.; Zhu, X.; Song, L.; Hong, M.; Guo, L. Prostate tumor overexpressed 1 (PTOV1) is a novel prognostic marker for nasopharyngeal carcinoma progression and poor survival outcomes. PLoS One, 2015, 10(8), e0136448.
[http://dx.doi.org/10.1371/journal.pone.0136448] [PMID: 26305455]
[12]
Shen, H.; Liao, B.; Wan, Z.; Zhao, Y.; You, Z.; Liu, J.; Lan, J.; He, S. PTOV1 promotes cisplatin-induced chemotherapy resistance by activating the nuclear factor kappa B pathway in ovarian cancer. Mol. Ther. Oncolytics, 2021, 20, 499-507.
[http://dx.doi.org/10.1016/j.omto.2021.02.008] [PMID: 33738336]
[13]
Cánovas, V.; Puñal, Y.; Maggio, V.; Redondo, E.; Marín, M.; Mellado, B.; Olivan, M.; Lleonart, M.; Planas, J.; Morote, J.; Paciucci, R. Prostate tumor overexpressed-1 (PTOV1) promotes docetaxel-resistance and survival of castration resistant prostate cancer cells. Oncotarget, 2017, 8(35), 59165-59180.
[http://dx.doi.org/10.18632/oncotarget.19467] [PMID: 28938627]
[14]
Wu, Z.; Liu, Z.; Jiang, X.; Mi, Z.; Meng, M.; Wang, H.; Zhao, J.; Zheng, B.; Yuan, Z. Depleting PTOV1 sensitizes non-small cell lung cancer cells to chemotherapy through attenuating cancer stem cell traits. J. Exp. Clin. Cancer Res., 2019, 38(1), 341.
[http://dx.doi.org/10.1186/s13046-019-1349-y] [PMID: 31387622]
[15]
Allina, D.O.; Andreeva, Y.Y.; Zavalishina, L.E.; Moskvina, L.V.; Frank, G.A. Estimation of the diagnostic potential of APOD, PTOV1, and EPHA4 for prostatic neoplasms. Arkh. Patol., 2016, 78(5), 9-14.
[http://dx.doi.org/10.17116/patol20167859-14] [PMID: 27804940]
[16]
Li, T.; Fu, J.; Zeng, Z.; Cohen, D.; Li, J.; Chen, Q.; Li, B.; Liu, X.S. TIMER2.0 for analysis of tumor-infiltrating immune cells. Nucleic Acids Res., 2020, 48(W1), W509-W514.
[http://dx.doi.org/10.1093/nar/gkaa407] [PMID: 32442275]
[17]
Tang, Z.; Kang, B.; Li, C.; Chen, T.; Zhang, Z. GEPIA2: An enhanced web server for large-scale expression profiling and interactive analysis. Nucleic Acids Res., 2019, 47(W1), W556-W560.
[http://dx.doi.org/10.1093/nar/gkz430] [PMID: 31114875]
[18]
Wu, C.; MacLeod, I.; Su, A.I. BioGPS and MyGene.info: Organizing online, gene-centric information. Nucleic Acids Res., 2013, 41(D1), D561-D565.
[http://dx.doi.org/10.1093/nar/gks1114] [PMID: 23175613]
[19]
Nagy, Á.; Munkácsy, G.; Győrffy, B. Pancancer survival analysis of cancer hallmark genes. Sci. Rep., 2021, 11(1), 6047.
[http://dx.doi.org/10.1038/s41598-021-84787-5] [PMID: 33723286]
[20]
Mizuno, H.; Kitada, K.; Nakai, K.; Sarai, A. PrognoScan: A new database for meta-analysis of the prognostic value of genes. BMC Med. Genomics, 2009, 2(1), 18.
[http://dx.doi.org/10.1186/1755-8794-2-18] [PMID: 19393097]
[21]
Gao, J.; Aksoy, B.A.; Dogrusoz, U.; Dresdner, G.; Gross, B.; Sumer, S.O.; Sun, Y.; Jacobsen, A.; Sinha, R.; Larsson, E.; Cerami, E.; Sander, C.; Schultz, N. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci. Signal., 2013, 6(269), 11.
[http://dx.doi.org/10.1126/scisignal.2004088] [PMID: 23550210]
[22]
Ru, B.; Wong, C.N.; Tong, Y.; Zhong, J.Y.; Zhong, S.S.W.; Wu, W.C.; Chu, K.C.; Wong, C.Y.; Lau, C.Y.; Chen, I.; Chan, N.W.; Zhang, J. TISIDB: An integrated repository portal for tumor–immune system interactions. Bioinformatics, 2019, 35(20), 4200-4202.
[http://dx.doi.org/10.1093/bioinformatics/btz210] [PMID: 30903160]
[23]
Hu, J.; Qiu, D.; Yu, A.; Hu, J.; Deng, H.; Li, H.; Yi, Z.; Chen, J.; Zu, X. YTHDF1 is a potential pan-cancer biomarker for prognosis and immunotherapy. Front. Oncol., 2021, 11, 607224.
[http://dx.doi.org/10.3389/fonc.2021.607224] [PMID: 34026603]
[24]
Szklarczyk, D.; Gable, A.L.; Nastou, K.C.; Lyon, D.; Kirsch, R.; Pyysalo, S.; Doncheva, N.T.; Legeay, M.; Fang, T.; Bork, P.; Jensen, L.J.; von Mering, C. The STRING database in 2021: Customizable protein–protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res., 2021, 49(D1), D605-D612.
[http://dx.doi.org/10.1093/nar/gkaa1074] [PMID: 33237311]
[25]
Cui, X.; Zhang, X.; Liu, M.; Zhao, C.; Zhang, N.; Ren, Y.; Su, C.; Zhang, W.; Sun, X.; He, J.; Gao, X.; Yang, J. A pan-cancer analysis of the oncogenic role of staphylococcal nuclease domain-containing protein 1 (SND1) in human tumors. Genomics, 2020, 112(6), 3958-3967.
[http://dx.doi.org/10.1016/j.ygeno.2020.06.044] [PMID: 32645525]
[26]
Sun, Y.; Sun, X.; Liu, S.; Liu, L.; Chen, J. The overlap between regeneration and fibrosis in injured skeletal muscle is regulated by phosphatidylinositol 3-kinase/Akt signaling pathway - A bioinformatic analysis based on lncRNA microarray. Gene, 2018, 672, 79-87.
[http://dx.doi.org/10.1016/j.gene.2018.06.001] [PMID: 29870770]
[27]
Loizides, S.; Constantinidou, A. Triple negative breast cancer: Immunogenicity, tumor microenvironment, and immunotherapy. Front. Genet., 2023, 13, 1095839-1095839.
[http://dx.doi.org/10.3389/fgene.2022.1095839] [PMID: 36712858]
[28]
Wang, L.H.; Wu, C.F.; Rajasekaran, N.; Shin, Y.K. Loss of tumor suppressor gene function in human cancer: An overview. Cell. Physiol. Biochem., 2018, 51(6), 2647-2693.
[http://dx.doi.org/10.1159/000495956] [PMID: 30562755]
[29]
Xu, D.; Liu, X.; Wang, Y.; Zhou, K.; Wu, J.; Chen, J.; Chen, C.; Chen, L.; Zheng, J. Identification of immune subtypes and prognosis of hepatocellular carcinoma based on immune checkpoint gene expression profile. Biomed. Pharmacother., 2020, 126, 109903.
[http://dx.doi.org/10.1016/j.biopha.2020.109903] [PMID: 32113055]
[30]
Dostert, C.; Grusdat, M.; Letellier, E.; Brenner, D. The TNF family of ligands and receptors: Communication modules in the immune system and beyond. Physiol. Rev., 2019, 99(1), 115-160.
[http://dx.doi.org/10.1152/physrev.00045.2017] [PMID: 30354964]
[31]
D’Assoro, A.; Leon-Ferre, R.; Braune, E.B.; Lendahl, U. Roles of notch signaling in the tumor microenvironment. Int. J. Mol. Sci., 2022, 23(11), 6241.
[http://dx.doi.org/10.3390/ijms23116241] [PMID: 35682918]
[32]
Cui, Y.; Ma, W.; Lei, F.; Li, Q.; Su, Y.; Lin, X.; Lin, C.; Zhang, X.; Ye, L.; Wu, S.; Li, J.; Yuan, Z.; Song, L. Prostate tumour overexpressed-1 promotes tumourigenicity in human breast cancer via activation of Wnt/β-catenin signalling. J. Pathol., 2016, 239(3), 297-308.
[http://dx.doi.org/10.1002/path.4725] [PMID: 27060981]
[33]
Chen, Y.; McAndrews, K.M.; Kalluri, R. Clinical and therapeutic relevance of cancer-associated fibroblasts. Nat. Rev. Clin. Oncol., 2021, 18(12), 792-804.
[http://dx.doi.org/10.1038/s41571-021-00546-5] [PMID: 34489603]
[34]
Ganesh, S.K.; Subathra Devi, C. Molecular and therapeutic insights of rapamycin: A multi-faceted drug from Streptomyces hygroscopicus. Mol. Biol. Rep., 2023, 50, 1-19.
[http://dx.doi.org/10.1007/s11033-023-08283-x] [PMID: 36696023]
[35]
Yang, R.; Yu, Y. Glucocorticoids are double-edged sword in the treatment of COVID-19 and cancers. Int. J. Biol. Sci., 2021, 17(6), 1530-1537.
[http://dx.doi.org/10.7150/ijbs.58695] [PMID: 33907516]
[36]
Edelman, G.; Rodon, J.; Lager, J.; Castell, C.; Jiang, J.; Van Allen, E.M.; Wagle, N.; Lindeman, N.I.; Sholl, L.M.; Shapiro, G.I.; Phase, I. Phase I trial of a tablet formulation of pilaralisib, a Pan-Class I PI3K inhibitor, in patients with advanced solid tumors. Oncologist, 2018, 23(4), 401-e38.
[http://dx.doi.org/10.1634/theoncologist.2017-0691] [PMID: 29593099]
[37]
Lim, J.S.; Ibaseta, A.; Fischer, M.M.; Cancilla, B.; O’Young, G.; Cristea, S.; Luca, V.C.; Yang, D.; Jahchan, N.S.; Hamard, C.; Antoine, M.; Wislez, M.; Kong, C.; Cain, J.; Liu, Y.W.; Kapoun, A.M.; Garcia, K.C.; Hoey, T.; Murriel, C.L.; Sage, J. Intratumoural heterogeneity generated by Notch signalling promotes small-cell lung cancer. Nature, 2017, 545(7654), 360-364.
[http://dx.doi.org/10.1038/nature22323] [PMID: 28489825]
[38]
Marqués, N.; Sesé, M.; Cánovas, V.; Valente, F.; Bermudo, R.; de Torres, I.; Fernández, Y.; Abasolo, I.; Fernández, P.L.; Contreras, H.; Castellón, E.; Celià-Terrassa, T.; Méndez, R.; Ramón y Cajal, S.; Thomson, T.M.; Paciucci, R. Regulation of protein translation and c-Jun expression by prostate tumor overexpressed 1. Oncogene, 2014, 33(9), 1124-1134.
[http://dx.doi.org/10.1038/onc.2013.51] [PMID: 23455324]
[39]
Karna, S.K.L.; Ahmad, F.; Lone, B.A.; Pokharel, Y.R. Knockdown of PTOV1 and PIN1 exhibit common phenotypic anti-cancer effects in MDA-MB-231 cells. PLoS One, 2019, 14(5), e0211658.
[http://dx.doi.org/10.1371/journal.pone.0211658] [PMID: 31083670]
[40]
Lei, F.; Zhang, L.; Li, X.; Lin, X.; Wu, S.; Li, F.; Liu, J. Overexpression of prostate tumor overexpressed 1 correlates with tumor progression and predicts poor prognosis in breast cancer. BMC Cancer, 2014, 14(1), 457.
[http://dx.doi.org/10.1186/1471-2407-14-457] [PMID: 24947166]
[41]
Ziani, L.; Chouaib, S.; Thiery, J. Alteration of the antitumor immune response by cancer-associated fibroblasts. Front. Immunol., 2018, 9, 414.
[http://dx.doi.org/10.3389/fimmu.2018.00414] [PMID: 29545811]
[42]
Liu, T.; Han, C.; Wang, S.; Fang, P.; Ma, Z.; Xu, L.; Yin, R. Cancer-associated fibroblasts: An emerging target of anti-cancer immunotherapy. J. Hematol. Oncol., 2019, 12(1), 86.
[http://dx.doi.org/10.1186/s13045-019-0770-1] [PMID: 31462327]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy