The role of phosphoprotein phosphatases catalytic subunit genes in pancreatic cancer

Hang, Junjie; Lau, Shun; Yin, Ruohan; Zhu, Lina; Zhou, Siyuan; Yuan, Xin; Wu, Lixia

doi:10.1042/bsr20203282

Cited by 12 publications

(10 citation statements)

References 47 publications

(50 reference statements)

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“…Finally, while the molecular function of phosphatase encoded by PPEF1 is not known in detail, it has been connected to apoptosis regulation and the response to calcium (Ca 2+ is also second messenger controlling cell death) 64 . It exerts a tumorigenic role in breast cancer 65 and was found to be overexpressed in pancreatic carcinoma 66 which confirms both its prognostic value in LUAD (poorer survival when highly expressed) and literature data regarding lung cancer 64 .…”

Section: Discussionsupporting

confidence: 77%

Prognostic significance of AP-2α/γ targets as cancer therapeutics

Kołat

Kałuzińska

Płuciennik

2022

Sci Rep

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Identifying genes with prognostic importance could improve cancer treatment. An increasing number of reports suggest the existence of successful strategies based on seemingly “untargetable” transcription factors. In addition to embryogenesis, AP-2 transcription factors are known to play crucial roles in cancer development. Members of this family can be used as prognostic factors in oncological patients, and AP-2α/γ transcription factors were previously investigated in our pan-cancer comparative study using their target genes. The present study investigates tumors that were previously found similar with an emphasis on the possible role of AP-2 factors in specific cancer types. The RData workspace was loaded back to R environment and 3D trajectories were built via Monocle3. The genes that met the requirement of specificity were listed using top_markers(), separately for mutual and unique targets. Furthermore, the candidate genes had to meet the following requirements: correlation with AP-2 factor (through Correlation AnalyzeR) and validated prognostic importance (using GEPIA2 and subsequently KM-plotter or LOGpc). Eventually, the ROC analysis was applied to confirm their predictive value; co-dependence of expression was visualized via BoxPlotR. Some similar tumors were differentiated by AP-2α/γ targets with prognostic value. Requirements were met by only fifteen genes (EMX2, COL7A1, GRIA1, KRT1, KRT14, SLC12A5, SEZ6L, PTPRN, SCG5, DPP6, NTSR1, ARX, COL4A3, PPEF1 and TMEM59L); of these, the last four were excluded based on ROC curves. All the above genes were confronted with the literature, with an emphasis on the possible role played by AP-2 factors in specific cancers. Following ROC analysis, the genes were verified using immunohistochemistry data and progression-related signatures. Staining differences were observed, as well as co-dependence on the expression of e.g. CTNNB1, ERBB2, KRAS, SMAD4, EGFR or MKI67. In conclusion, prognostic value of targets suggested AP-2α/γ as candidates for novel cancer treatment. It was also revealed that AP-2 targets are related to tumor progression and that some mutual target genes could be inversely regulated.

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Section: Discussionsupporting

confidence: 77%

Prognostic significance of AP-2α/γ targets as cancer therapeutics

Kołat

Kałuzińska

Płuciennik

2022

Sci Rep

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“…The PPP2CA gene encodes the α subtype of the PP2A catalytic subunit, which regulates PP2A activity by selecting PP2A regulatory subunits (12). In previous studies, the upregulation of PPP2CA was considered to be related to the poor prognosis of triple-negative breast cancer (13) and pancreatic cancer (14). High expression of PPP2CA is also related to glioma, and mir-130b-ceRNA can promote the epithelial-mesenchymal transition and invasion of glioma by targeting PPP2CA (15).…”

Section: Discussionmentioning

confidence: 99%

The effect of PPP2CA expression on the prognosis of patients with hepatocellular carcinoma and its molecular biological characteristics

Liang¹,

Huang²,

Yang³

et al. 2021

J Gastrointest Oncol

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Background: To investigate the role of the PPP2CA gene in the prognosis of patients with hepatocellular carcinoma (HCC) and its molecular biological characteristics. Methods: We performed comparison of the expression of PPP2CA in HCC and non-HCC tissues of HCC patients who underwent surgery for the first time in the Tumor Hospital of Guangxi Medical University from July 2017 to July 2019, and retrospectively analyzed the relevant clinical data and prognosis. The GSE76427 data set and bioinformatics and public databases were used to compare the expression of PPP2CA between HCC and non-cancer tissues. Gene Ontology (GO) analysis was performed of PPP2CA and its differential genes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. A protein-protein interaction (PPI) network of PPP2CA and its differentially expressed genes (DEGs) was constructed from the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database and visualized by Cytoscape software. Results: The immunohistochemistry (IHC) of tissue sections confirmed that PPP2CA was highly expressed in most HCC tissues; the high expression of PPP2CA was significantly correlated with microvascular invasion (MVI) and portal vein tumor thrombi (P<0.05). Participants in the PPP2CA high expression group had worse overall survival (OS; P=0.04) and recurrence-free survival (RFS; P=0.019). The PPP2CA gene and 71 DEGs were mainly enriched in the nuclear division, organelle fission, nuclear chromosome separation, and chromatid separation process, and KEGG analysis revealed enrichment in drug metabolism-cytochrome metabolism of xenobiotics by P450 and cytochrome P450. Finally, through the PPI network, CCNA2, AURKB, TOP2A, NCAPG, MCM2, CDC20, CCMB2, AURKA, and MGST1 were identified as the top 9 highly connected hub genes. Conclusions:The PPP2CA gene is highly expressed in HCC tissues. The high expression of PPP2CA is significantly associated with poor prognosis. Through the analysis of DEGs, GO and KEGG pathway analysis, it was found that PPP2CA may act on liver cancer through multiple targets and multiple pathways, and PPP2CA plays a promoting role in HCC.

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“…Our findings support the hypothesis that PPP1CB facilitates the progression of PAAD. The expression of PPP1CB [16] .…”

Section: Discussionmentioning

confidence: 99%

“…These data demonstrate that the expression levels of PPP1CB in PAAD tissue may have prognostic significance in predicting outcomes for patients with PAAD. In recent years, it has been reported that PPP1CA, PPP1CB, PPP2CA, PPP2CB , and PPP3CA accelerate the progression of pancreatic cancer, while PPP3CB, PPP5C , and PPP6C hinder PAAD progression [ 16 ] .…”

Section: Discussionmentioning

confidence: 99%

“…As a regulator of endothelial cell migration, PPP1CB may be an effective target for anti-angiogenic therapy and inhibition of tumor growth [ 15 ]. Additionally, PPP1CA, PPP1CB, PPP2CA, PPP2CB , and PPP3CA facilitate PAAD progression, while PPP3CB, PPP5C , and PPP6C inhibit PAAD progression, however the role of PPP1CB has not been thoroughly investigated [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

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The expression and clinical prognostic value of protein phosphatase 1 catalytic subunit beta in pancreatic cancer

Wang

et al. 2021

Bioengineered

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Pancreatic cancer (PAAD) is a common malignancy with a poor survival rate. The identification of novel biomarkers could improve clinical outcomes for patients with PAAD. Here we evaluated the expression and clinical significance of PPP1CB in PAAD. PPP1CB expression was higher in PAAD tissue than in matched paracancerous tissue (P < 0.05). We predicted a network of regulatory targets and protein interaction partners of PPP1CB, and identified a PPI network consisting of 39 node genes. The expression of 33 node genes was higher in PAAD tissue than in matching paracancerous tissue. High expression of the node genes ACTN4, ANLN, CLTB, IQGAP1, SPTAN1, and TMOD3 was associated with improved overall survival (P < 0.05). SiRNA knockdown of PPP1CB significantly reduced the migration and invasion of PAAD cells. A PPP1CB immunohistochemical staining was performed using a tissue microarray (TMA), consisting of tumor samples collected from 91 patients with PAAD (88 of which contained matched paracancerous tissues). The expression of PPP1CB in PAAD was significantly higher than in the matched paracancerous tissue, (P = 0.016). High PPP1CB expression was associated with patient sex (P = 0.048), alcohol use (P = 0.039), CEA (P= 0.038), N stage (P = 0.001), and invasion of nerve (P = 0.036). Furthermore, high PPP1CB expression was associated with significantly poorer overall survival (P = 0.022). Our data demonstrate that PPP1CB is associated with the migration and invasion of PAAD cells, and may be useful as an independent prognostic indicator for clinical outcome in patients with PAAD.

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The role of phosphoprotein phosphatases catalytic subunit genes in pancreatic cancer

Cited by 12 publications

References 47 publications

Prognostic significance of AP-2α/γ targets as cancer therapeutics

Prognostic significance of AP-2α/γ targets as cancer therapeutics

The effect of PPP2CA expression on the prognosis of patients with hepatocellular carcinoma and its molecular biological characteristics

The expression and clinical prognostic value of protein phosphatase 1 catalytic subunit beta in pancreatic cancer

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