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BMC Cancer
Published in: BMC Cancer 1/2023

Open Access 01-12-2023 | Biomarkers | Research

ORC6, a novel prognostic biomarker, correlates with T regulatory cell infiltration in prostate adenocarcinoma: a pan-cancer analysis

Authors: Yuan Lin, Ying Zhang, Zhouting Tuo, Liang Gao, Demao Ding, Liangkuan Bi, Dexin Yu, Zhengmei Lv, Jiani Wang, Xin Chen

Published in: BMC Cancer | Issue 1/2023

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Abstract

Background

The origin recognition complex (ORC), a six-subunit DNA-binding complex, participates in DNA replication in cancer cells. Specifically in prostate cancers, ORC participates the androgen receptor (AR) regulated genomic amplification and tumor proliferation throughout the entire cell cycle. Of note, ORC6, the smallest subunit of ORC, has been reported to be dysregulated in some types of cancers (including prostate cancer), however, its prognostic and immunological significances remain yet to be elucidated.

Methods

In the current study, we comprehensively investigated the potential prognostic and immunological role of ORC6 in 33 human tumors using multiple databases, such as TCGA, Genotype-Tissue Expression, CCLE, UCSC Xena, cBioPortal, Human Protein Atlas, GeneCards, STRING, MSigDB, TISIDB, and TIMER2 databases.

Results

ORC6 expression was significantly upregulated in 29 types of cancers compared to the corresponding normal adjacent tissues. ORC6 overexpression correlated with higher stage and worse prognostic outcomes in most cancer types analyzed. Additionally, ORC6 was involved in the cell cycle pathway, DNA replication, and mismatch repair pathways in most tumor types. A negative correlation was observed between the tumor endothelial cell infiltration and ORC6 expression in almost all tumors, whereas the immune infiltration of T regulatory cell was noted to be statistically positively correlated with the expression of ORC6 in prostate cancer tissues. Furthermore, in most tumor types, immunosuppression-related genes, especially TGFBR1 and PD-L1 (CD274), exhibited a specific correlation with the expression of ORC6.

Conclusions

This comprehensive pan-cancer analysis revealed that ORC6 expression serves as a prognostic biomarker and that ORC6 is involved in the regulation of various biological pathways, the tumor microenvironment, and the immunosuppression status in several human cancers, suggesting its potential diagnostic, prognostic, and therapeutic value in pan-cancer, especially in prostate adenocarcinoma.
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Literature
1.
2.
3.
Thomae AW, Baltin J, Pich D, Deutsch MJ, Ravasz M, Zeller K, Gossen M, Hammerschmidt W, Schepers A. Different roles of the human Orc6 protein in the replication initiation process. Cell Mol Life Sci. 2011;68(22):3741–56.PubMedCrossRef
4.
Hu Y, Wang L, Li Z, Wan Z, Shao M, Wu S, Wang G. Potential Prognostic and Diagnostic Values of CDC6, CDC45, ORC6 and SNHG7 in Colorectal Cancer. Onco Targets Ther. 2019;12:11609–21.PubMedPubMedCentralCrossRef
5.
Chen H, Bao L, Hu J, Wu D, Tong X. ORC6, Negatively Regulated by miR-1-3p, Promotes Proliferation, Migration, and Invasion of Hepatocellular Carcinoma Cells. Front Cell Dev Biol. 2021;9:652292.PubMedPubMedCentralCrossRef
6.
Gavin EJ, Song B, Wang Y, Xi Y, Ju J. Reduction of Orc6 expression sensitizes human colon cancer cells to 5-fluorouracil and cisplatin. PLoS ONE. 2008;3(12):e4054.PubMedPubMedCentralCrossRef
7.
Mao R, Wang Z, Zhang Y, Chen Y, Liu Q, Zhang T, Liu Y. Development and validation of a novel prognostic signature in gastric adenocarcinoma. Aging. 2020;12(21):22233–52.PubMedCrossRef
8.
Fujita K, Nonomura N. Role of Androgen Receptor in Prostate Cancer: A Review. World J Men’s Health. 2019;37(3):288–95.
9.
10.
D’Antonio JM, Vander Griend DJ, Isaacs JT. DNA licensing as a novel androgen receptor mediated therapeutic target for prostate cancer. Endocr Relat Cancer. 2009;16(2):325–32.
11.
Wei J, Yin Y, Deng Q, Zhou J, Wang Y, Yin G, Yang J, Tang Y. Integrative Analysis of MicroRNA and Gene Interactions for Revealing Candidate Signatures in Prostate Cancer. Front Genet. 2020;11:176.PubMedPubMedCentralCrossRef
12.
Huo G, Wang Y, Chen J, Song Y, Zhang C, Guo H, Zuo R, Zhu F, Cui J, Chen W, et al. A Pan-Cancer Analysis of the Oncogenic Role of Twinfilin Actin Binding Protein 1 in Human Tumors. Front Oncol. 2021;11:692136.PubMedPubMedCentralCrossRef
13.
Kamal Y, Dwan D, Hoehn HJ, Sanz-Pamplona R, Alonso MH, Moreno V, Cheng C, Schell MJ, Kim Y, Felder SI, et al. Tumor immune infiltration estimated from gene expression profiles predicts colorectal cancer relapse. Oncoimmunology. 2021;10(1):1862529.PubMedPubMedCentralCrossRef
14.
15.
Chen F, Fan Y, Cao P, Liu B, Hou J, Zhang B, Tan K. Pan-Cancer Analysis of the Prognostic and Immunological Role of HSF1: A Potential Target for Survival and Immunotherapy. Oxid Med Cell Longev. 2021;2021:5551036.PubMedPubMedCentral
16.
Thorsson V, Gibbs DL, Brown SD, Wolf D, Bortone DS, Ou Yang TH, Porta-Pardo E, Gao GF, Plaisier CL, Eddy JA, et al. The Immune Landscape of Cancer. Immunity. 2018;48(4):812-830 e814.PubMedPubMedCentralCrossRef
17.
18.
19.
Kanehisa M, Furumichi M, Sato Y, Ishiguro-Watanabe M, Tanabe M. KEGG: integrating viruses and cellular organisms. Nucleic Acids Res. 2021;49(D1):D545–51.PubMedCrossRef
20.
Kanehisa M, Furumichi M, Sato Y, Kawashima M, Ishiguro-Watanabe M. KEGG for taxonomy-based analysis of pathways and genomes. Nucleic Acids Res. 2023;51(D1):D587–92.PubMedCrossRef
21.
Chen X, Bernemann C, Tolkach Y, Heller M, Nientiedt C, Falkenstein M, Herpel E, Jenzer M, Grullich C, Jager D, et al. Overexpression of nuclear AR-V7 protein in primary prostate cancer is an independent negative prognostic marker in men with high-risk disease receiving adjuvant therapy. Urologic oncology. 2018;36(4):161 e119-161 e130.CrossRef
22.
Dong B, Wu C, Li SH, Huang L, Zhang C, Wu B, Sheng Y, Liu Y, Ye G, Qi Y. Correlation of m6A methylation with immune infiltrates and poor prognosis in non-small cell lung cancer via a comprehensive analysis of RNA expression profiles. Ann Transl Med. 2021;9(18):1465.PubMedPubMedCentralCrossRef
23.
Fu Y, Wei X, Han Q, Le J, Ma Y, Lin X, Xu Y, Liu N, Wang X, Kong X, et al. Identification and characterization of a 25-lncRNA prognostic signature for early recurrence in hepatocellular carcinoma. BMC Cancer. 2021;21(1):1165.PubMedPubMedCentralCrossRef
24.
Thiemeyer H, Taher L, Schille JT, Packeiser EM, Harder LK, Hewicker-Trautwein M, Brenig B, Schutz E, Beck J, Nolte I, et al. An RNA-Seq-Based Framework for Characterizing Canine Prostate Cancer and Prioritizing Clinically Relevant Biomarker Candidate Genes. Int J Mol Sci. 2021;22(21):11481.
25.
Zhang K, Fu G, Pan G, Li C, Shen L, Hu R, Zhu S, Chen Y, Cui H. Demethylzeylasteral inhibits glioma growth by regulating the miR-30e-5p/MYBL2 axis. Cell Death Dis. 2018;9(10):1035.PubMedPubMedCentralCrossRef
26.
Prasanth SG, Prasanth KV, Stillman B. Orc6 involved in DNA replication, chromosome segregation, and cytokinesis. Science. 2002;297(5583):1026–31.PubMedCrossRef
27.
Pan Q, Li F, Ding Y, Huang H, Guo J. ORC6 acts as a biomarker and reflects poor outcome in clear cell renal cell carcinoma. J Cancer. 2022;13(8):2504–14.PubMedPubMedCentralCrossRef
28.
Jardim DL, Goodman A, de Melo GD, Kurzrock R. The Challenges of Tumor Mutational Burden as an Immunotherapy Biomarker. Cancer Cell. 2021;39(2):154–73.PubMedCrossRef
29.
Jiang Z, Yin W, Zhu H, Tan J, Guo Y, Xin Z, Zhou Q, Cao Y, Wu Z, Kuang Y, et al. METTL7B is a novel prognostic biomarker of lower-grade glioma based on pan-cancer analysis. Cancer Cell Int. 2021;21(1):383.PubMedPubMedCentralCrossRef
30.
31.
Marabelle A, Fakih M, Lopez J, Shah M, Shapira-Frommer R, Nakagawa K, Chung HC, Kindler HL, Lopez-Martin JA, Miller WH Jr, et al. Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study. Lancet Oncol. 2020;21(10):1353–65.PubMedCrossRef
32.
33.
Forde PM, Chaft JE, Smith KN, Anagnostou V, Cottrell TR, Hellmann MD, Zahurak M, Yang SC, Jones DR, Broderick S, et al. Neoadjuvant PD-1 Blockade in Resectable Lung Cancer. N Engl J Med. 2018;378(21):1976–86.PubMedPubMedCentralCrossRef
34.
Mandal R, Samstein RM, Lee KW, Havel JJ, Wang H, Krishna C, Sabio EY, Makarov V, Kuo F, Blecua P, et al. Genetic diversity of tumors with mismatch repair deficiency influences anti-PD-1 immunotherapy response. Science. 2019;364(6439):485–91.PubMedPubMedCentralCrossRef
35.
Overman MJ, McDermott R, Leach JL, Lonardi S, Lenz HJ, Morse MA, Desai J, Hill A, Axelson M, Moss RA, et al. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. Lancet Oncol. 2017;18(9):1182–91.PubMedPubMedCentralCrossRef
36.
Zhao P, Li L, Jiang X, Li Q. Mismatch repair deficiency/microsatellite instability-high as a predictor for anti-PD-1/PD-L1 immunotherapy efficacy. J Hematol Oncol. 2019;12(1):54.PubMedPubMedCentralCrossRef
37.
Paz-Ares L, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Ozguroglu M, Ji JH, et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019;394(10212):1929–39.PubMedCrossRef
38.
Dummer R, Ascierto PA, Gogas HJ, Arance A, Mandala M, Liszkay G, Garbe C, Schadendorf D, Krajsova I, Gutzmer R, et al. Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2018;19(5):603–15.PubMedCrossRef
39.
40.
Liu J-Q, Deng M, Xue N-N, Li T-X, Guo Y-X, Gao L, Zhao D, Fan R-T. lncRNA KLF3-AS1 suppresses cell migration and invasion in ESCC by impairing miR-185-5p-targeted KLF3 inhibition. Mol Ther Nucleic Acids. 2020;20:231–41.PubMedPubMedCentralCrossRef
41.
Liu J, Xue N, Guo Y, Niu K, Gao L, Zhang S, Gu H, Wang X, Zhao D, Fan R. CircRNA_100367 regulated the radiation sensitivity of esophageal squamous cell carcinomas through miR-217/Wnt3 pathway. Aging (Albany NY). 2019;11(24):12412–27.PubMedCrossRef
42.
Feng D, Zhang F, Li D, Shi X, Xiong Q, Wei Q, Yang L. Developing an immune-related gene prognostic index associated with progression and providing new insights into the tumor immune microenvironment of prostate cancer. Immunology. 2022;166(2):197–209.PubMedCrossRef
43.
Song W, Ren J, Xiang R, Kong C, Fu T. Identification of pyroptosis-related subtypes, the development of a prognosis model, and characterization of tumor microenvironment infiltration in colorectal cancer. Oncoimmunology. 2021;10(1):1987636.PubMedPubMedCentralCrossRef
44.
Ino Y, Yamazaki-Itoh R, Shimada K, Iwasaki M, Kosuge T, Kanai Y, Hiraoka N. Immune cell infiltration as an indicator of the immune microenvironment of pancreatic cancer. Br J Cancer. 2013;108(4):914–23.PubMedPubMedCentralCrossRef
45.
Remark R, Becker C, Gomez JE, Damotte D, Dieu-Nosjean MC, Sautes-Fridman C, Fridman WH, Powell CA, Altorki NK, Merad M, et al. The non-small cell lung cancer immune contexture. A major determinant of tumor characteristics and patient outcome. Am J Respir Crit Care Med. 2015;191(4):377–90.PubMedPubMedCentralCrossRef
46.
Feng D, Xiong Q, Wei Q, Yang L. Cellular landscape of tumour microenvironment in prostate cancer. Immunology. 2023;168(2):199–202.PubMedCrossRef
47.
Fridman WH, Galon J, Dieu-Nosjean MC, Cremer I, Fisson S, Damotte D, Pages F, Tartour E, Sautes-Fridman C. Immune infiltration in human cancer: prognostic significance and disease control. Curr Top Microbiol Immunol. 2011;344:1–24.PubMed
48.
49.
Xue N, Zhou R, Deng M, Li Y, Hu Y, Gao L, Zhang Y, Song X, Liu J, Fan R. High serum superoxide dismutase activity improves radiation-related quality of life in patients with esophageal squamous cell carcinoma. Clinics (Sao Paulo). 2021;76:e2226.PubMedCrossRef
50.
Chen X, Song E. Turning foes to friends: targeting cancer-associated fibroblasts. Nat Rev Drug Discovery. 2019;18(2):99–115.PubMedCrossRef
51.
Biffi G, Tuveson DA. Diversity and Biology of Cancer-Associated Fibroblasts. Physiol Rev. 2021;101(1):147–76.PubMedCrossRef
52.
Nagl L, Horvath L, Pircher A, Wolf D. Tumor Endothelial Cells (TECs) as Potential Immune Directors of the Tumor Microenvironment - New Findings and Future Perspectives. Front Cell Dev Biol. 2020;8:766.PubMedPubMedCentralCrossRef
53.
54.
Shevyrev D, Tereshchenko V. Treg Heterogeneity, Function, and Homeostasis. Front Immunol. 2019;10:3100.PubMedCrossRef
55.
Farhood B, Najafi M, Mortezaee K. CD8(+) cytotoxic T lymphocytes in cancer immunotherapy: A review. J Cell Physiol. 2019;234(6):8509–21.PubMedCrossRef
56.
Karpisheh V, Mousavi SM, NaghaviSheykholeslami P, Fathi M, MohammadpourSaray M, Aghebati-Maleki L, Jafari R, MajidiZolbanin N, Jadidi-Niaragh F. The role of regulatory T cells in the pathogenesis and treatment of prostate cancer. Life Sci. 2021;284:119132.PubMedCrossRef
Metadata
Title
ORC6, a novel prognostic biomarker, correlates with T regulatory cell infiltration in prostate adenocarcinoma: a pan-cancer analysis
Authors
Yuan Lin
Ying Zhang
Zhouting Tuo
Liang Gao
Demao Ding
Liangkuan Bi
Dexin Yu
Zhengmei Lv
Jiani Wang
Xin Chen
Publication date
01-12-2023
Publisher
BioMed Central
Keyword
Biomarkers
Published in
BMC Cancer / Issue 1/2023
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-023-10763-z

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