Bionformatics analysis reveals TSPAN1 as a candidate biomarker of progression and prognosis in pancreatic cancer

Ma, Chenhui; Cui, Zelong; Wang, YiChao; Zhang, Lei; Wen, Jiaxin; Guo, Huaibin; Li, Na; Zhang, Wanxing

doi:10.17305/bjbms.2020.5096

Cited by 8 publications

(7 citation statements)

References 53 publications

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“…Another study has identified TSPAN1 as one of the potential diagnostic markers and was expressed at a high level in PC tissues and cells, which was consistent with our study results [ 19 ]. Ma C et al identified TSPAN1 could be involved in PC progression and act as a critical biomarker for diagnosing and predicting patient survival with PC through weighted gene co-expression network analysis [ 20 ]. Even so, the role of TSPAN1 in the prognosis of PC is not yet clear.…”

Section: Discussionmentioning

confidence: 99%

Screening and Validation of Independent Predictors of Poor Survival in Pancreatic Cancer

Shui

Cai

Changyong

et al. 2021

Pathol. Oncol. Res.

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Pancreatic cancer is a digestive system malignant tumor with high mortality and poor prognosis, but the mechanisms of progression remain unclear in pancreatic cancer. It’s necessary to identify the hub genes in pancreatic cancer and explore the novel potential predictors in the prognosis of pancreatic cancer. We downloaded two mRNA expression profiles from Gene Expression Omnibus and The Cancer Genome Atlas Pancreatic Cancer (TCGA-PAAD) datasets to screen the commonly differentially expressed genes in pancreatic cancer by limma package in R. Subsequently, measurement of the functional similarity among the 38 DEGs in common was performed to identify the hub genes using GOSemSim package. Then, survival analysis and Cox regression were applied to explore prognosis-related hub genes using the survival package. Statistics analysis by two-tailed Student’s t-test or one-way based on TCGA-PAAD datasets and qPCR detection in clinical samples were performed to explore the correlations between expression of hub genes in pancreatic cancer tissues and clinical parameters. Based on integrated analysis of TCGA and GEO datasets, we screened 38 DEGs in common, which were all up-regulated. The functional similarity results showed that 10 DEGs including TSPAN1, MSLN, C1orf116, PKP3, CEACAM6, BAIAP2L1, PPL, RAB25, ERBB3, and AP1M2 in the DEGs in common, which had the higher average functional similarity, were considered as the hub genes. Survival analysis results and Cox regression analysis showed that TSPAN1, CEACAM6, as well as ERBB3 were all associated with poor overall survival of PC. qPCR results showed that the expression levels of TSPAN1 and ERBB3 were significantly upregulated in the PC tissues. The statistical analysis results revealed that TSPAN1 expression correlated significantly with histologic grade, T stage, clinical stage, and vital status by two-tailed Student’s t-test or one-way ANOVA; ERBB3 expression correlated significantly with T stage, clinical stage, and vital status by two-tailed Student’s t-test or one-way ANOVA. We found that TSPAN1 and ERBB3 could be independent predictors of poor survival in pancreatic cancer.

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Section: Discussionmentioning

confidence: 99%

Screening and Validation of Independent Predictors of Poor Survival in Pancreatic Cancer

Shui

Cai

Changyong

et al. 2021

Pathol. Oncol. Res.

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“…TSPAN1 is a transmembrane protein that has been reported to be elevated in many human cancers and to be involved in tumor progression [8][9][10][11][12]. According to our previous RNA-Seq with TSPAN1overexpressing, shTSPAN1 and their corresponding control PANC-1 cells.…”

Section: Fam110a Is An Essential Target Of Tspan1 Pdacmentioning

confidence: 99%

“…Tetraspanin 1 (TSPAN1) is a member of the tetraspanin family, which is a family of small transmembrane proteins. TSPAN1 has been reported to be elevated in many human cancers and to be involved in tumor progression [8][9][10][11][12]. Our previous study has revealed that TSPAN1 is an oncogene that promotes cell proliferation, migration, invasion and tumorigenesis in PDAC [8].…”

Section: Introductionmentioning

confidence: 99%

TSPAN1-elevated FAM110A promotes pancreatic cancer progression by transcriptionally regulating HIST1H2BK

Huang¹,

Li²,

Zhao³

et al. 2022

J. Cancer

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Background: FAM110A belongs to the FAM110 family, which mainly functions in biological processes associated with the cell cycle. However, the biological functions in which FAM110A participates are largely undefined. In particular, its potential role in cancer remains unknown. The goal of this study was to uncover the role and mechanism of FAM110A in pancreatic cancer. Methods: Based on bioinformatics databases, qPCR and Western blot assays, we verified the elevated expression level of FAM110A in PDAC. Subsequently, FAM110A, HIST1H2BK and TSPAN1 overexpression or knockdown stable transfected cells were employed for biological functions' studies to explore the role in PDAC in vitro and in vivo. RNA-Seq, Western blot and luciferase-reporter assays were used to explore mechanism of FAM110A action in PDAC, and the involved pathway was verified by tumor phenotypic rescue experiments. Results: In this study, we demonstrated for the first time that FAM110A is an oncogene that promotes cell proliferation, migration, invasion and tumorigenesis in pancreatic cancer. HIST1H2BK was identified as the downstream target of FAM110A, while the promotion effect caused by FAM110A overexpression could be abolished by HIST1H2BK knockdown. Moreover, for the first time, we revealed the oncogenic role of HIST1H2BK in pancreatic cancer, and the tumor-promoting capacity of HIST1H2BK may be associated with its regulatory effect on G9a. In addition, we demonstrated that TSPAN1 displayed a positive transcriptional regulatory effect on FAM110A. Conclusions: Collectively, FAM110A plays an oncogenic role in PDAC, and the newly identified TSPAN1/FAM110A/HIST1H2BK/G9a pathway is involved in the modulation of pancreatic cancer progression and provides a novel prognostic and therapeutic strategy for pancreatic cancer treatment.

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“…Tetraspanin1 TSPAN-1, NET-1 Intestine, testis Regulation of cell development, activation, growth and motility (Liu et al, 2019;Wang L. et al, 2021). Prognostic role in prostate (Stinnesbeck et al, 2021), pancreatic (Ma C. et al, 2021), and cervical (Wollscheid et al, 2002) cancer Plays an important role in normal bladder epithelial physiology (Wu et al, 1995;Lobban et al, 1998;Ogawa et al, 1999;Hall et al, 2005). Upregulation connected with lung cancer cells (Byun et al, 2020), downregulation enhances apoptosis of bladder carcinoma cells (Zhu et al, 2015) and reduced expression associated with gastric adenocarcinoma (Zheng et al, 2014) Tetraspanin22 TSPAN22, PRPH2, CACD2, rd2, RDS, RP7, Peripherin 2 Retina Essential for retina photoreceptor outer segment disk morphogenesis (Donato et al, 2021) and involved in retinal degeneration (Travis et al, 1991), macular dystrophy (Kumaran et al, 1993;Çavdarli et al, 2020) and retinitis pigmentosa (Kajiwara et al, 1991;Farrar et al, 1992;Jordan et al, 1992; Tetraspanin23 TSPAN23, ROM1, ROM, Retinal outer segment membrane protein 1 Retina Plays a role in rod outer segment (ROS) morphogenesis (Conley et al, 2017).…”

Section: Protein Functionmentioning

confidence: 99%

Tetraspanins as Potential Modulators of Glutamatergic Synaptic Function

Becic

Leifeld

Shaukat

et al. 2022

Front. Mol. Neurosci.

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Tetraspanins (Tspans) comprise a membrane protein family structurally defined by four transmembrane domains and intracellular N and C termini that is found in almost all cell types and tissues of eukaryotes. Moreover, they are involved in a bewildering multitude of diverse biological processes such as cell adhesion, motility, protein trafficking, signaling, proliferation, and regulation of the immune system. Beside their physiological roles, they are linked to many pathophysiological phenomena, including tumor progression regulation, HIV-1 replication, diabetes, and hepatitis. Tetraspanins are involved in the formation of extensive protein networks, through interactions not only with themselves but also with numerous other specific proteins, including regulatory proteins in the central nervous system (CNS). Interestingly, recent studies showed that Tspan7 impacts dendritic spine formation, glutamatergic synaptic transmission and plasticity, and that Tspan6 is correlated with epilepsy and intellectual disability (formerly known as mental retardation), highlighting the importance of particular tetraspanins and their involvement in critical processes in the CNS. In this review, we summarize the current knowledge of tetraspanin functions in the brain, with a particular focus on their impact on glutamatergic neurotransmission. In addition, we compare available resolved structures of tetraspanin family members to those of auxiliary proteins of glutamate receptors that are known for their modulatory effects.

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Bionformatics analysis reveals TSPAN1 as a candidate biomarker of progression and prognosis in pancreatic cancer

Cited by 8 publications

References 53 publications

Screening and Validation of Independent Predictors of Poor Survival in Pancreatic Cancer

Screening and Validation of Independent Predictors of Poor Survival in Pancreatic Cancer

TSPAN1-elevated FAM110A promotes pancreatic cancer progression by transcriptionally regulating HIST1H2BK

Tetraspanins as Potential Modulators of Glutamatergic Synaptic Function

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