PPIH acts as a potential predictive biomarker for patients with common solid tumors.
Humans
Biomarkers, Tumor
/ blood
Prognosis
Female
Liver Neoplasms
/ genetics
Gene Expression Regulation, Neoplastic
Carcinoma, Hepatocellular
/ genetics
Neoplasms
/ genetics
Male
Computational Biology
/ methods
RNA, Messenger
/ genetics
Kaplan-Meier Estimate
Breast Neoplasms
/ genetics
Stomach Neoplasms
/ genetics
Colonic Neoplasms
/ genetics
Gene Regulatory Networks
PPIH
Combined diagnosis
Common solid tumors
Predictive biomarker
TCGA
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
04 Jun 2024
04 Jun 2024
Historique:
received:
22
02
2024
accepted:
28
05
2024
medline:
5
6
2024
pubmed:
5
6
2024
entrez:
4
6
2024
Statut:
epublish
Résumé
Our previous studies have indicated that mRNA and protein levels of PPIH are significantly upregulated in Hepatocellular Carcinoma (LIHC) and could act as predictive biomarkers for patients with LIHC. Nonetheless, the expression and implications of PPIH in the etiology and progression of common solid tumors have yet to be explored, including its potential as a serum tumor marker. We employed bioinformatics analyses, augmented with clinical sample evaluations, to investigate the mRNA and protein expression and gene regulation networks of PPIH in various solid tumors. We also assessed the association between PPIH expression and overall survival (OS) in cancer patients using Kaplan-Meier analysis with TCGA database information. Furthermore, we evaluated the feasibility and diagnostic efficacy of PPIH as a serum marker by integrating serological studies with established clinical tumor markers. Through pan-cancer analysis, we found that the expression levels of PPIH mRNA in multiple tumors were significantly different from those in normal tissues. This study is the first to report that PPIH mRNA and protein levels are markedly elevated in LIHC, Colon adenocarcinoma (COAD), and Breast cancer (BC), and are associated with a worse prognosis in these cancer patients. Conversely, serum PPIH levels are decreased in patients with these tumors (LIHC, COAD, BC, gastric cancer), and when combined with traditional tumor markers, offer enhanced sensitivity and specificity for diagnosis. Our findings propose that PPIH may serve as a valuable predictive biomarker in tumor patients, and its secreted protein could be a potential serum marker, providing insights into the role of PPIH in cancer development and progression.
Sections du résumé
BACKGROUND
BACKGROUND
Our previous studies have indicated that mRNA and protein levels of PPIH are significantly upregulated in Hepatocellular Carcinoma (LIHC) and could act as predictive biomarkers for patients with LIHC. Nonetheless, the expression and implications of PPIH in the etiology and progression of common solid tumors have yet to be explored, including its potential as a serum tumor marker.
METHODS
METHODS
We employed bioinformatics analyses, augmented with clinical sample evaluations, to investigate the mRNA and protein expression and gene regulation networks of PPIH in various solid tumors. We also assessed the association between PPIH expression and overall survival (OS) in cancer patients using Kaplan-Meier analysis with TCGA database information. Furthermore, we evaluated the feasibility and diagnostic efficacy of PPIH as a serum marker by integrating serological studies with established clinical tumor markers.
RESULTS
RESULTS
Through pan-cancer analysis, we found that the expression levels of PPIH mRNA in multiple tumors were significantly different from those in normal tissues. This study is the first to report that PPIH mRNA and protein levels are markedly elevated in LIHC, Colon adenocarcinoma (COAD), and Breast cancer (BC), and are associated with a worse prognosis in these cancer patients. Conversely, serum PPIH levels are decreased in patients with these tumors (LIHC, COAD, BC, gastric cancer), and when combined with traditional tumor markers, offer enhanced sensitivity and specificity for diagnosis.
CONCLUSION
CONCLUSIONS
Our findings propose that PPIH may serve as a valuable predictive biomarker in tumor patients, and its secreted protein could be a potential serum marker, providing insights into the role of PPIH in cancer development and progression.
Identifiants
pubmed: 38834966
doi: 10.1186/s12885-024-12446-9
pii: 10.1186/s12885-024-12446-9
doi:
Substances chimiques
Biomarkers, Tumor
0
RNA, Messenger
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
681Informations de copyright
© 2024. The Author(s).
Références
Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022;72(1):7–33.
doi: 10.3322/caac.21708
pubmed: 35020204
Morad G, Helmink BA, Sharma P, Wargo JA. Hallmarks of response, resistance, and toxicity to immune checkpoint blockade. Cell. 2021;184(21):5309–37.
pubmed: 34624224
pmcid: 8767569
doi: 10.1016/j.cell.2021.09.020
Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade. Science. 2018;359(6382):1350–5.
pubmed: 29567705
pmcid: 7391259
doi: 10.1126/science.aar4060
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7–34.
Liu B, Fan Y, Song Z, et al. Identification of DRP1 as a prognostic factor correlated with immune infiltration in breast cancer. Int Immunopharmacol. 2020;89Pt B:107078.
doi: 10.1016/j.intimp.2020.107078
Horowitz DS, Lee EJ, Mabon SA, Misteli T. A cyclophilin functions in pre-mRNA splicing. EMBO J. 2002;21(3):470–80.
pubmed: 11823439
pmcid: 125845
doi: 10.1093/emboj/21.3.470
Teigelkamp S, Achsel T, Mundt C, et al. The 20kD protein of human [U4/U6.U5] tri-snRNPs is a novel cyclophilin that forms a complex with the U4/U6-specific 60kD and 90kD proteins. RNA. 1998;4(2):127–41.
pubmed: 9570313
pmcid: 1369602
Rajiv C, Jackson SR, Cocklin S, Eisenmesser EZ, Davis TL. The spliceosomal proteins PPIH and PRPF4 exhibit bi-partite binding. Biochem J. 2017;474(21):3689–704.
pubmed: 28935721
doi: 10.1042/BCJ20170366
Wahl MC, Will CL, Lührmann R. The spliceosome: design principles of a dynamic RNP machine. Cell. 2009;136(4):701–18.
pubmed: 19239890
doi: 10.1016/j.cell.2009.02.009
Li J, Zhou W, Wei J, Xiao X, An T, Wu W, et al. Prognostic Value and Biological functions of RNA binding proteins in stomach adenocarcinoma. Onco Targets Ther. 2021;14:1689–705.
pubmed: 33707953
pmcid: 7942957
doi: 10.2147/OTT.S297973
Gao L, Li GS, Li JD, et al. Identification of the susceptibility genes for COVID-19 in lung adenocarcinoma with global data and biological computation methods. Comput Struct Biotechnol J. 2021;19:6229–39.
pubmed: 34840672
pmcid: 8605816
doi: 10.1016/j.csbj.2021.11.026
Li M, Liu Z, Wang J, et al. Systematic analysis identifies a specific RNA-Binding protein-related Gene Model for Prognostication and Risk-Adjustment in HBV-Related Hepatocellular Carcinoma. Front Genet. 2021;12:707305.
pubmed: 34422009
pmcid: 8371711
doi: 10.3389/fgene.2021.707305
Ye J, Pang Y, Yang X, et al. PPIH gene regulation system and its prognostic significance in hepatocellular carcinoma: a comprehensive analysis. Aging. 2023;15(20):11448–70.
pubmed: 37874737
pmcid: 10637785
Pang Y, Tan G, Yang X, et al. Iron-sulphur cluster biogenesis factor LYRM4 is a novel prognostic biomarker associated with immune infiltrates in hepatocellular carcinoma. Cancer Cell Int. 2021;21(1):463.
pubmed: 34488769
pmcid: 8419973
doi: 10.1186/s12935-021-02131-3
Chen Y, Xie H, Xie T, Yang X, Pang Y, Ye S. Elevated expression of PDZD11 is Associated with Poor Prognosis and Immune infiltrates in Hepatocellular Carcinoma. Front Genet. 2021;12:669928.
pubmed: 34093661
pmcid: 8176286
doi: 10.3389/fgene.2021.669928
Ou Q, Ma N, Yu Z, et al. Nudix hydrolase 1 is a prognostic biomarker in hepatocellular carcinoma. Aging. 2020;12(8):7363–79.
pubmed: 32341205
pmcid: 7202498
doi: 10.18632/aging.103083
Wyatt C, Pernaute B, Gohr A, et al. A developmentally programmed splicing failure contributes to DNA damage response attenuation during mammalian zygotic genome activation. Sci Adv. 2022;8(15):eabn4935.
pubmed: 35417229
pmcid: 9007516
doi: 10.1126/sciadv.abn4935
Luo Q, Zhang L, Luo C, Jiang M. Emerging strategies in cancer therapy combining chemotherapy with immunotherapy. Cancer Lett. 2019;454:191–203.
pubmed: 30998963
doi: 10.1016/j.canlet.2019.04.017
Brown ZJ, Tsilimigras DI, Ruff SM, et al. Management of Hepatocellular Carcinoma: a review. JAMA Surg. 2023;158(4):410–20.
pubmed: 36790767
doi: 10.1001/jamasurg.2022.7989
Duran SR, Jaquiss R. Hepatocellular Carcinoma. N Engl J Med. 2019;381(1):e2.
pubmed: 31269386
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.
pubmed: 30207593
doi: 10.3322/caac.21492
López MJ, Carbajal J, Alfaro AL, et al. Characteristics of gastric cancer around the world. Crit Rev Oncol Hematol. 2023;181:103841.
pubmed: 36240980
doi: 10.1016/j.critrevonc.2022.103841
Harbeck N, Penault-Llorca F, Cortes J, et al. Breast cancer. Nat Rev Dis Primers. 2019;5(1):66.
pubmed: 31548545
doi: 10.1038/s41572-019-0111-2
Sung H, Ferlay J, Siegel RL, et al. Global Cancer statistics 2020: GLOBOCAN estimates of incidence and Mortality Worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49.
pubmed: 33538338
doi: 10.3322/caac.21660
Nguyen TB, Do DN, Nguyen-Thanh T, Tatipamula VB, Nguyen HT. Identification of Five Hub Genes as key prognostic biomarkers in Liver Cancer via Integrated Bioinformatics Analysis. Biology (Basel). 2021;10(10):957.
pubmed: 34681056
Peng L, Jiang J, Chen HN, et al. Redox-sensitive cyclophilin a elicits chemoresistance through realigning cellular oxidative status in colorectal cancer. Cell Rep. 2021;37(9):110069.
pubmed: 34852234
doi: 10.1016/j.celrep.2021.110069
Guichard C, Amaddeo G, Imbeaud S, et al. Integrated analysis of somatic mutations and focal copy-number changes identifies key genes and pathways in hepatocellular carcinoma. Nat Genet. 2012;44(6):694–8.
pubmed: 22561517
pmcid: 3819251
doi: 10.1038/ng.2256
Lin Y, Liang R, Qiu Y, et al. Expression and gene regulation network of RBM8A in hepatocellular carcinoma based on data mining. Aging. 2019;11(2):423–47.
pubmed: 30670676
pmcid: 6366983
doi: 10.18632/aging.101749
Zhuang D, Liang L, Zhang H, Feng X. miR-202 suppresses Hepatocellular Carcinoma Progression via Downregulating BCL2 expression. Oncol Res. 2020;28(4):399–408.
pubmed: 32272979
pmcid: 7851524
doi: 10.3727/096504020X15864296270581
Zhai J, Qu S, Li X, et al. miR-129 suppresses tumor cell growth and invasion by targeting PAK5 in hepatocellular carcinoma. Biochem Biophys Res Commun. 2015;464(1):161–7.
pubmed: 26116538
doi: 10.1016/j.bbrc.2015.06.108
Zhao Y, Xu Z, Zhou J, Yang H. miR–141 inhibits proliferation, migration and invasion in human hepatocellular carcinoma cells by directly downregulating TGFβR1. Oncol Rep. 2019;42(5):1656–66.
pubmed: 31545479
Liu W, Zheng L, Zhang R, et al. Circ-ZEB1 promotes PIK3CA expression by silencing miR-199a-3p and affects the proliferation and apoptosis of hepatocellular carcinoma. Mol Cancer. 2022;21(1):72.
pubmed: 35277182
pmcid: 8915544
doi: 10.1186/s12943-022-01529-5
Wang W, Lin H, Zhou L, et al. MicroRNA-30a-3p inhibits tumor proliferation, invasiveness and metastasis and is downregulated in hepatocellular carcinoma. Eur J Surg Oncol. 2014;40(11):1586–94.
pubmed: 24290372
doi: 10.1016/j.ejso.2013.11.008
Ma C, Huang S, Xu L, Tian L, Yang Y, Wang J. Transcription co-activator P300 activates Elk1-aPKC-ι signaling mediated epithelial-to-mesenchymal transition and malignancy in hepatocellular carcinoma. Oncogenesis. 2020;9(3):32.
pubmed: 32144235
pmcid: 7060348
doi: 10.1038/s41389-020-0212-5
Tang Z, Gu Y, Shi Z, et al. Multiplex immune profiling reveals the role of serum immune proteomics in predicting response to preoperative chemotherapy of gastric cancer. Cell Rep Med. 2023;4(2):100931.
pubmed: 36724786
pmcid: 9975277
doi: 10.1016/j.xcrm.2023.100931
Qi F, Zhou A, Yan L, et al. The diagnostic value of PIVKA-II, AFP, AFP-L3, CEA, and their combinations in primary and metastatic hepatocellular carcinoma. J Clin Lab Anal. 2020;34(5):e23158.
pubmed: 31821607
doi: 10.1002/jcla.23158
Lu Q, Li J, Cao H, Lv C, Wang X, Cao S. Comparison of diagnostic accuracy of Midkine and AFP for detecting hepatocellular carcinoma: a systematic review and meta-analysis. Biosci Rep. 2020;40(3):BSR20192424.
pubmed: 32039435
pmcid: 7087326
doi: 10.1042/BSR20192424
Li L, Shao M, Peng P, et al. High expression of GFAT1 predicts unfavorable prognosis in patients with hepatocellular carcinoma. Oncotarget. 2017;8(12):19205–17.
pubmed: 28186970
pmcid: 5386678
doi: 10.18632/oncotarget.15164
Feng F, Tian Y, Xu G, et al. Diagnostic and prognostic value of CEA, CA19-9, AFP and CA125 for early gastric cancer. BMC Cancer. 2017;17(1):737.
pubmed: 29121872
pmcid: 5679342
doi: 10.1186/s12885-017-3738-y
Wang W, Chen XL, Zhao SY, et al. Prognostic significance of preoperative serum CA125, CA19-9 and CEA in gastric carcinoma. Oncotarget. 2016;7(23):35423–36.
pubmed: 27097114
pmcid: 5085240
doi: 10.18632/oncotarget.8770
Song X, Liang B, Wang C, Shi S. Clinical value of color doppler ultrasound combined with serum CA153, CEA and TSGF detection in the diagnosis of breast cancer. Exp Ther Med. 2020;20(2):1822–8.
pubmed: 32742414
pmcid: 7388249
doi: 10.3892/etm.2020.8868
Zhang XO, Dong R, Zhang Y, et al. Diverse alternative back-splicing and alternative splicing landscape of circular RNAs. Genome Res. 2016;26(9):1277–87.
pubmed: 27365365
pmcid: 5052039
doi: 10.1101/gr.202895.115
Kristensen LS, Jakobsen T, Hager H, Kjems J. The emerging roles of circRNAs in cancer and oncology. Nat Rev Clin Oncol. 2022;19(3):188–206.
pubmed: 34912049
doi: 10.1038/s41571-021-00585-y
Qi L, Wang W, Zhao G et al. Circular RNA circitga7 accelerates glioma progression via miR-34a-5p/VEGFA axis. Aging (Albany NY). 2021. 13(9): 13138–52.
Killela PJ, Pirozzi CJ, Healy P, et al. Mutations in IDH1, IDH2, and in the TERT promoter define clinically distinct subgroups of adult malignant gliomas. Oncotarget. 2014;5(6):1515–25.
pubmed: 24722048
pmcid: 4039228
doi: 10.18632/oncotarget.1765
Huang A, Zheng H, Wu Z, Chen M, Huang Y. Circular RNA-protein interactions: functions, mechanisms, and identification. Theranostics. 2020;10(8):3503–17.
pubmed: 32206104
pmcid: 7069073
doi: 10.7150/thno.42174