354P - Decreased INPP5B expression predicts poor prognosis in lung adenocarcinoma

Background

INPP5B, a inositol 5-phosphatase, plays an important role in many biological processes through phosphorylating PI(4,5)P₂ and/or PI(3,4,5)P₃ at the 5-position. Nevertheless, little is known about its function and cellular pathways in tumors. This study aims to investigate the potential role of INPP5B as a diagnostic and prognostic biomarker for lung adenocarcinoma (LUAD), as well as its biological functions and molecular mechanisms in LUAD.

Methods

TCGA, GEO, CTPAC, and HPA datasets were used for differential expression analysis and pathological stratification comparison. The prognostic and diagnostic role of INPP5B was determined by Kaplan-Meier curves, univariate and multivariate Cox regression analysis, and receiver operating characteristics (ROC) curve analyses. The potential mechanism of INPP5B was explored through GO, KEGG, and GSEA enrichment analysis, as well as GeneMANIA and STRING protein-protein interaction (PPI) network. PicTar, PITA, and miRmap databases were used for exploring miRNA targeting INPP5B. In molecular biology experiments, immunohistochemical analyses and Western blot analyses were used to determine protein expression. Co-immunoprecipitation assay was used to detect protein-protein interactions.

Results

INPP5B was decreased in LUAD tissues compared with normal adjacent tissues. And the low expression of INPP5B was associated with late-stage pathological features. In addition, INPP5B was found to be a significant independent prognostic and diagnostic factor for LUAD patients. Hsa-miR-582-5p was predicted as a negative regulator of INPP5B mRNA expression. INPP5B was significantly correlated with the expression of PTEN and the activity of PI3K/AKT signaling pathways, as determined by enrichment analysis and PPI network. In vitro experiments partially confirmed the aforementioned findings. INPP5B could interact directly with PTEN to inhibit the phosphorylation of PTEN. INPP5B overexpression inhibited LUAD cell proliferation and migration while downregulating the AKT pathway.

Conclusions

Our results demonstrated that INPP5B could inhibit the proliferation and metastasis of LUAD cells. It could serve as a novel diagnostic and prognostic biomarker for LUAD patients.

Clinical trial identification

LUAD tissues and corresponding para-cancerous tissues were collected from 10 different LUAD patients at Hangzhou First People’s Hospital. The Ethics Committee of Hangzhou First People's Hospital has approved this study. (registration number:ⅡT-20210907-0031-01;registration date:2021.09.13).

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

This study was funded by National Natural Science Foundation of China (81702887), Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province (2020E10021), Zhejiang Provincial Natural Science Foundation(LY19H310004,LTY21H160001), Scientific and Technological Developing Scheme of Hangzhou City (20191203B49), Science Research Foundation of Zhejiang Health Bureau (2020RC026).

Disclosure

All authors have declared no conflicts of interest.