Abstract
Purpose
Plasmalemma vesicle-associated protein (PLVAP) is involved in many immune‑related signals; however, its role in stomach adenocarcinoma (STAD) remains to be elucidated. This study investigated PLVAP expression in tumor tissues and defined the value in STAD patients.
Methods
A total of 96 patient paraffin-embedded STAD specimens and 30 paraffin-embedded adjacent non-tumor specimens from the Ninth Hospital of Xi’an were consecutively recruited in analyses. All RNA‑sequence data were available from the Cancer Genome Atlas database (TCGA). PLVAP protein expression was detected using immunohistochemistry. Microbial community analysis was performed by 16S rRNA gene sequencing using Illumina MiSeq. PLVAP mRNA expression was explored with the Tumor Immune Estimation Resource (TIMER), GEPIA, and UALCAN databases. The effect of PLVAP mRNA on prognosis was analyzed via GEPIA, and Kaplan–Meier plotter database. GeneMANIA and STRING databases were used to predict gene/protein interactions and functions. The relationships between PLVAP mRNA expression and tumor-infiltrated immune cells were analyzed via the TIMER and GEPIA databases.
Results
Significantly elevated transcriptional and proteomic PLVAP expressions were found in STAD samples. Increased PLVAP protein and mRNA expression were significantly associated with advanced clinicopathological parameters and correlated with shorter disease-free survival (DFS) and overall survival (OS) in TCGA (P < 0.001). The microbiota in the PLVAP-rich (3+) group was significantly different from that in the PLVAP-poor (1+) group (P < 0.05). The results from TIMER showed that high PLVAP mRNA expression had significant positive correlations with CD4 + T cell (r = 0.42, P < 0.001).
Conclusion
PLVAP is a potential biomarker to predict the prognosis of patients with STAD, and the high level of PLVAP protein expression was closely related to bacteria. The relative abundance of Fusobacteriia was positvely associated with the level of PLVAP. In conclusion, positive staining for PLVAP was useful for predicting the poor prognosis of STAD with Fusobacteriia infection.
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Data availability
The data underlying this study will be shared on request to the corresponding author.
Abbreviations
- PLVAP:
-
Plasmalemma vesicle-associated protein
- STAD:
-
Stomach adenocarcinoma
- TCGA:
-
The Cancer Genome Atlas
- IHC:
-
Immunohistochemistry
- OUT:
-
Operational taxonomic units
- KEGG:
-
Kyoto Encyclopedia of Genes and Genomes
- DFS:
-
Disease-free survival
- OS:
-
Overall survival
- TME:
-
Tumor microenvironment
- 16S rRNA:
-
16S ribosomal RNA
- KM:
-
Kaplan–Meier
- TIMER:
-
Tumor immune estimation resource
- MVD:
-
Microvessel density
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Funding
This research is supported by Ninth Hospital of Xi’an (Grant Reference Number 2022qn02); The Foundation of Xi’an science and technology project (No. 21YXYJ0069); the science research project of Xi’an traditional Chinese medicine (No. SZY202203).
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Yu.W. collected and analyzed all data, performed the statistics, drafted the initial manuscript, and reviewed the final version. Z.L. and C.H. were involved in data collection and reviewed the manuscript. Y.W. and Y.H. conceptualized and designed the study. Yu.W., Y.W., and Y.H. supervised the data collection, reviewed, and revised the manuscript.
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Wen, Y., Wang, Y., Huang, Y. et al. PLVAP protein expression correlated with microbial composition, clinicopathological features, and prognosis of patients with stomach adenocarcinoma. J Cancer Res Clin Oncol 149, 7139–7153 (2023). https://doi.org/10.1007/s00432-023-04607-3
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DOI: https://doi.org/10.1007/s00432-023-04607-3