Skip to content
2000
Volume 25, Issue 10
  • ISSN: 1568-0096
  • E-ISSN: 1873-5576

Abstract

Objective

This study aimed to investigate the expression pattern of phosphatidylinositol 3-kinase class III (PIK3C3/vps34) in gastric cancer (GC) tissues and their juxtaposed normal counterparts and its correlation with the clinicopathological attributes and prognostic outlook of afflicted individuals.

Methods

Immunohistochemical (IHC) staining was used to ascertain the expression levels of PIK3C3/vps34 across 60 GC tissues juxtaposed with their normal counterparts. Statistical methodologies were used to scrutinize the correlation between PIK3C3/vps34 expression and clinicopathological features, along with prognostic implications for GC patients.

Results

In GC tissues, the positive expression rate of PIK3C3/vps34 was 23.3% (14/60), which contrasted sharply with the markedly elevated rate of 66.7% (40/60) observed in adjacent tissues. The positive expression proportion of PIK3C3/vps34 within GC tissues exhibited a notable decrease than in adjacent tissues ( 0.05). The expression of PIK3C3/vps34 inversely correlated with tumor size, degree of tissue differentiation, depth of tumor infiltration, and incidence of lymph node metastasis ( 0.05), whereas no significant associations were found with patient sex, age, tumor location, TNM staging, or distant metastasis ( 0.05). As the tumor diameter increases, the degree of tissue differentiation diminishes, tumor infiltration depth intensifies, lymph node metastasis emerges, the TNM stage progresses, and PIK3C3/vps34 expression level within GC tissues declines correspondingly. Kaplan-Meier survival analysis unveiled a prolonged survival duration among GC patients exhibiting heightened PIK3C3/vps34 expression than in their counterparts with diminished expression (HR=0.66, 95% CI: 0.55-0.80), demonstrating statistical significance ( 0.05). Protein interaction analysis revealed noteworthy interactions involving PIK3C3 with Beclin 1, UVRAG, and ATG14.

Conclusion

PIK3C3/vps34 is downregulated in GC tissues, exerting a pivotal role in tumorigenesis, and is intimately linked with the prognostic trajectory of GC patients. It may serve as a significant biomarker for prognostic evaluation and a promising molecular therapeutic target for GC.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/ccdt/10.2174/0115680096334160240916102105
2024-10-01
2025-12-25

  • From This Site

    /content/journals/ccdt/10.2174/0115680096334160240916102105
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. SungH. FerlayJ. SiegelR.L. LaversanneM. SoerjomataramI. JemalA. BrayF. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries.CA Cancer J. Clin.202171320924910.3322/caac.21660 33538338
     [Google Scholar]
  2. FengR.M. ZongY.N. CaoS.M. XuR.H. Current cancer situation in China: good or bad news from the 2018 Global Cancer Statistics?Cancer Commun. (Lond.)201939111210.1186/s40880‑019‑0368‑6 31030667
     [Google Scholar]
  3. ZhangX. PengY. JinZ. HuangW. ChengY. LiuY. FengX. YangM. HuangY. ZhaoZ. WangL. WeiY. FanX. ZhengD. MeltzerS.J. Integrated miRNA profiling and bioinformatics analyses reveal potential causative miRNAs in gastric adenocarcinoma.Oncotarget2015632328783288910.18632/oncotarget.5419 26460735
     [Google Scholar]
  4. EllsonC.D. AndrewsS. StephensL.R. HawkinsP.T. The PX domain: a new phosphoinositide-binding module.J. Cell Sci.200211561099110510.1242/jcs.115.6.1099 11884510
     [Google Scholar]
  5. VirbasiusJ.V. SongX. PomerleauD.P. ZhanY. ZhouG.W. CzechM.P. Activation of the Akt-related cytokine-independent survival kinase requires interaction of its phox domain with endosomal phosphatidylinositol 3-phosphate.Proc. Natl. Acad. Sci. USA20019823129081291310.1073/pnas.221352898 11606732
     [Google Scholar]
  6. DaydeD. GuerardM. PerronP. HatatA-S. BarrialC. EyminB. GazzeriS. Nuclear trafficking of EGFR by Vps34 represses Arf expression to promote lung tumor cell survival.Oncogene201635303986399410.1038/onc.2015.480 26686095
     [Google Scholar]
  7. LvQ. WangW. XueJ. HuaF. MuR. LinH. YanJ. LvX. ChenX. HuZ.W. DEDD interacts with PI3KC3 to activate autophagy and attenuate epithelial-mesenchymal transition in human breast cancer.Cancer Res.201272133238325010.1158/0008‑5472.CAN‑11‑3832 22719072
     [Google Scholar]
  8. BarthaÁ. GyőrffyB. TNMplot.com: A Web Tool for the Comparison of Gene Expression in Normal, Tumor and Metastatic Tissues.Int. J. Mol. Sci.2021225262210.3390/ijms22052622 33807717
     [Google Scholar]
  9. PostaM. GyőrffyB. Analysis of a large cohort of pancreatic cancer transcriptomic profiles to reveal the strongest prognostic factors.Clin. Transl. Sci.20231681479149110.1111/cts.13563 37260110
     [Google Scholar]
  10. SzklarczykD. KirschR. KoutrouliM. NastouK. MehryaryF. HachilifR. GableA.L. FangT. DonchevaN.T. PyysaloS. BorkP. JensenL.J. von MeringC. The STRING database in 2023: protein–protein association networks and functional enrichment analyses for any sequenced genome of interest.Nucleic Acids Res.202351D1D638D64610.1093/nar/gkac1000 36370105
     [Google Scholar]
  11. KampfC. OlssonI. RybergU. SjöstedtE. PonténF. Production of tissue microarrays, immunohistochemistry staining and digitalization within the human protein atlas.J. Vis. Exp.20126363362010.3791/362022688270
     [Google Scholar]
  12. GaoJ.P. XuW. LiuW.T. YanM. ZhuZ.G. Tumor heterogeneity of gastric cancer: From the perspective of tumor-initiating cell.World J. Gastroenterol.201824242567258110.3748/wjg.v24.i24.2567 29962814
     [Google Scholar]
  13. MachlowskaJ. BajJ. SitarzM. MaciejewskiR. SitarzR. Gastric Cancer: Epidemiology, Risk Factors, Classification, Genomic Characteristics and Treatment Strategies.Int. J. Mol. Sci.20202111401210.3390/ijms21114012 32512697
     [Google Scholar]
  14. MunsonM.J. GanleyI.G. MTOR, PIK3C3, and autophagy: Signaling the beginning from the end.Autophagy201511122375237610.1080/15548627.2015.1106668 26565689
     [Google Scholar]
  15. OhashiY. Activation Mechanisms of the VPS34 Complexes.Cells202110113124312410.3390/cells10113124 34831348
     [Google Scholar]
  16. LiuY. YangQ. ChenS. LiZ. FuL. Targeting VPS34 in autophagy: An update on pharmacological small-molecule compounds.Eur. J. Med. Chem.202325611546710.1016/j.ejmech.2023.115467 37178482
     [Google Scholar]
  17. OhashiY. TremelS. WilliamsR.L. VPS34 complexes from a structural perspective.J. Lipid Res.201960222924110.1194/jlr.R089490 30397185
     [Google Scholar]
  18. BackerJ.M. The intricate regulation and complex functions of the Class III phosphoinositide 3-kinase Vps34.Biochem. J.2016473152251227110.1042/BCJ20160170 27470591
     [Google Scholar]
  19. LawF. RocheleauC.E. Vps34 and the Armus/TBC-2 Rab GAPs: Putting the brakes on the endosomal Rab5 and Rab7 GTPases.Cell. Logist.201774e140353010.1080/21592799.2017.1403530 29296513
     [Google Scholar]
  20. WangX. GuM. JuY. ZhouJ. Overcoming radio-resistance in esophageal squamous cell carcinoma via hypermethylation of PIK3C3 promoter region mediated by KDM5B loss.J. Radiat. Res. (Tokyo)202263333134110.1093/jrr/rrac004 35333349
     [Google Scholar]
  21. XieW. JinS. CuiJ. The NEDD4-USP13 axis facilitates autophagy via deubiquitinating PIK3C3.Autophagy20201661150115110.1080/15548627.2020.1743071 32174250
     [Google Scholar]
  22. SuH. LiuW. PIK3C3/VPS34 control by acetylation.Autophagy20181461086108710.1080/15548627.2017.1385676 28980854
     [Google Scholar]
  23. FunderburkS.F. WangQ.J. YueZ. The Beclin 1–VPS34 complex – at the crossroads of autophagy and beyond.Trends Cell Biol.201020635536210.1016/j.tcb.2010.03.002 20356743
     [Google Scholar]
  24. SongW. PostoakJ.L. YangG. GuoX. PuaH.H. BaderJ. RathmellJ.C. KobayashiH. HaaseV.H. LeaptrotK.L. Schrimpe-RutledgeA.C. SherrodS.D. McLeanJ.A. ZhangJ. WuL. Van KaerL. Lipid kinase PIK3C3 maintains healthy brown and white adipose tissues to prevent metabolic diseases.Proc. Natl. Acad. Sci. USA20231201e221487412010.1073/pnas.2214874120 36574710
     [Google Scholar]
  25. QiC. ZouL. WangS. MaoX. HuY. ShiJ. ZhangZ. WuH. Vps34 Inhibits Hepatocellular Carcinoma Invasion by Regulating Endosome-Lysosome Trafficking via Rab7-RILP and Rab11.Cancer Res. Treat.202254118219810.4143/crt.2020.578 33781048
     [Google Scholar]
  26. WangX. GuM. JuY. ZhouJ. PIK3C3 Acts as a Tumor Suppressor in Esophageal Squamous Cell Carcinoma and Was Regulated by MiR-340-5p.Med. Sci. Monit.202026e92064210.12659/MSM.920642 32207410
     [Google Scholar]
  27. WangH. YuanH. GuoQ. ZengX. LiuM. JiR. ChenZ. GuanQ. ZhengY. WangY. ZhouY. A novel circRNA, hsa_circ_0069382, regulates gastric cancer progression.Cancer Cell Int.20232313510.1186/s12935‑023‑02871‑4 36841760
     [Google Scholar]
  28. HamidiA.A. TaghehchianN. ZangoueiA.S. AkhlaghipourI. MaharatiA. BasiratZ. MoghbeliM. Molecular mechanisms of microRNA-216a during tumor progression.Cancer Cell Int.20232311910.1186/s12935‑023‑02865‑2 36740668
     [Google Scholar]
  29. GuoZ. ZhangY. XuW. ZhangX. JiangJ. Engineered exosome-mediated delivery of circDIDO1 inhibits gastric cancer progression via regulation of MiR-1307-3p/SOCS2 Axis.J. Transl. Med.202220132610.1186/s12967‑022‑03527‑z35864511
     [Google Scholar]
/content/journals/ccdt/10.2174/0115680096334160240916102105
Loading
Expression, Characteristics, and Clinical Target Prediction of PIK3C3/ vps34 in Gastric Cancer
Curr. Cancer Drug Targets< 25, 1298 (2025); https://doi.org/10.2174/0115680096334160240916102105
/content/journals/ccdt/10.2174/0115680096334160240916102105
/content/journals/ccdt/10.2174/0115680096334160240916102105
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher's website along with the published article.

file format download Download

  • Article Type:     Research Article
Keyword(s): Bioinformatics analysis; Gastric cancer; Immunohistochemistry; PIK3C3/vps34; Prognosis; UVRAG

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test