Signature identification of relapse-related overall survival of early lung adenocarcinoma after radical surgery

Han, Peng; Yue, Jiaqi; Kong, Kangle; Huang, Shan; Cao, Pei; Deng, Yu; Фан, Ли; Zhao, Bo

doi:10.7717/peerj.11923

Cited by 3 publications

(1 citation statement)

References 71 publications

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“…This was partially supported by a recent study that was published when we were preparing the current manuscript. Han et al [ 27 ] developed a four-gene signature including INPP5B which could effectively predict the recurrence of early lung cancer patients and associated survival chances following surgery. However, their study was based on a model of multi-gene signatures.…”

Section: Discussionmentioning

confidence: 99%

Decreased INPP5B expression predicts poor prognosis in lung adenocarcinoma

Deng

Lin

et al. 2022

Cancer Cell Int

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Background Inositol Polyphosphate-5-Phosphatase B (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. CCK8 assays and colony formation assays were used for the measurement of cell proliferation. Cell cycle was assessed by PI staining with flow cytometry. Cell migration was performed by Transwell assays and wound healing assays. Result 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. INPP5B overexpression inhibited LUAD cell proliferation and migration while downregulating the AKT pathway. Conclusion 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. Trial registration 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)

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Section: Discussionmentioning

confidence: 99%

Decreased INPP5B expression predicts poor prognosis in lung adenocarcinoma

Deng

Lin

et al. 2022

Cancer Cell Int

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MiRNA-144–5p down-modulates CDCA3 to regulate proliferation and apoptosis of lung adenocarcinoma cells

Luo

Xia²,

Zhang³

et al. 2022

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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Edge-based relative entropy as a sensitive indicator of critical transitions in biological systems

Hong,

Tong,

Liu

et al. 2024

J Transl Med

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Background Disease progression in biosystems is not always a steady process but is occasionally abrupt. It is important but challenging to signal critical transitions in complex biosystems. Methods In this study, based on the theoretical framework of dynamic network biomarkers (DNBs), we propose a model-free method, edge-based relative entropy (ERE), to identify temporal key biomolecular associations/networks that may serve as DNBs and detect early-warning signals of the drastic state transition during disease progression in complex biological systems. Specifically, by combining gene‒gene interaction (edge) information with the relative entropy, the ERE method converts gene expression values into network entropy values, quantifying the dynamic change in a biomolecular network and indicating the qualitative shift in the system state. Results The proposed method was validated using simulated data and real biological datasets of complex diseases. The applications show that for certain diseases, the ERE method helps to reveal so-called “dark genes” that are non-differentially expressed but with high ERE values and of essential importance in both gene regulation and prognosis. Conclusions The proposed method effectively identified the critical transition states of complex diseases at the network level. Our study not only identified the critical transition states of various cancers but also provided two types of new prognostic biomarkers, positive and negative edge biomarkers, for further practical application. The method in this study therefore has great potential in personalized disease diagnosis.

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Signature identification of relapse-related overall survival of early lung adenocarcinoma after radical surgery

Cited by 3 publications

References 71 publications

Decreased INPP5B expression predicts poor prognosis in lung adenocarcinoma

Decreased INPP5B expression predicts poor prognosis in lung adenocarcinoma

MiRNA-144–5p down-modulates CDCA3 to regulate proliferation and apoptosis of lung adenocarcinoma cells

Edge-based relative entropy as a sensitive indicator of critical transitions in biological systems

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