Expression of platelet-derived endothelial cell growth factor/thymidine phosphorylase in cervical intraepithelial neoplasia

Isaka, Shigeyuki; Sawai, Keisuke; Tomiie, Mari; Kamiura, Shoji; Koyama, Masayasu; Azuma, Chihiro; Ishiguro, Shingo; Murata, Yuji; Saji, Fumitaka

doi:10.3892/ijo.21.2.281

Cited by 5 publications

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“…91 TYPH is highly expressed in microvessels of CIN and SCC and appears to be involved in angiogenesis in CIN. 92 TYPH activity is increased in invasive cervical SCC, with the highest level in lymph node metastases. 93 Based on these analyses, we demonstrated that the data of iTRAQ-based proteomics were not only supported by the qRT-PCR and IHC verification, and bioinformatic evaluation, but also highly consistent with earlier findings.…”

Section: Discussionmentioning

confidence: 94%

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Proteomic identification of potential biomarkers for cervical squamous cell carcinoma and human papillomavirus infection

Song

Tulake

et al. 2017

Tumour Biol.

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It is known that high-risk human papillomavirus infection is the main etiological factor in cervical carcinogenesis. However, human papillomavirus screening is not sufficient for early diagnosis. In this study, we aimed to identify potential biomarkers common to cervical carcinoma and human papillomavirus infection by proteomics for human papillomavirus-based early diagnosis and prognosis. To this end, we collected 76 cases of fresh cervical tissues and 116 cases of paraffin-embedded tissue slices, diagnosed as cervical squamous cell carcinoma, cervical intraepithelial neoplasia II-III, or normal cervix from ethnic Uighur and Han women. Human papillomavirus infection by eight oncogenic human papillomavirus types was detected in tissue DNA samples using a quantitative polymerase chain reaction. The protein profile of cervical specimens from human papillomavirus 16-positive squamous cell carcinoma and human papillomavirus-negative normal controls was analyzed by proteomics and bioinformatics. The expression of candidate proteins was further determined by quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry. We identified 67 proteins that were differentially expressed in human papillomavirus 16-positive squamous cell carcinoma compared to normal cervix. The quantitative reverse transcriptase-polymerase chain reaction analysis verified the upregulation of ASAH1, PCBP2, DDX5, MCM5, TAGLN2, hnRNPA1, ENO1, TYPH, CYC, and MCM4 in squamous cell carcinoma compared to normal cervix (p < 0.05). In addition, the transcription of PCBP2, MCM5, hnRNPA1, TYPH, and CYC was also significantly increased in cervical intraepithelial neoplasia II-III compared to normal cervix. Immunohistochemistry staining further confirmed the overexpression of PCBP2, hnRNPA1, ASAH1, and DDX5 in squamous cell carcinoma and cervical intraepithelial neoplasia II-III compared to normal controls (p < 0.05). Our data suggest that the expression of ASAH1, PCBP2, DDX5, and hnRNPA1, and possibly MCM4, MCM5, CYC, ENO1, and TYPH, is upregulated during cervical carcinogenesis and potentially associated with human papillomavirus infection. Further validation studies of the profile will contribute to establishing auxiliary diagnostic markers for human papillomavirus-based cancer prognosis. KeywordsCervical carcinoma, isobaric tags for relative and absolute quantitation, proteomics, human papillomavirus infection, cervical specimen Date

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 94%

Proteomic identification of potential biomarkers for cervical squamous cell carcinoma and human papillomavirus infection

Song

Tulake

et al. 2017

Tumour Biol.

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“…It has also been suggested that TP expression in interstitial cells has an important role in tumor vascularity for patients with stage IIB to IVB uterine cervical carcinomas and that the abundance of microvessels is an independent prognostic factor (12,13) . TP expression in tumor cells is reported to have no relation with vascularization 14 ; yet, it is said to be associated with increasing tumor diameter, invasiveness, and metastasis to lymph nodes (15–18) . TP expression in tumor cells is further suggested to significantly elevate microvessel density and to be a poor prognostic factor (19,20) .…”

Section: Discussionmentioning

confidence: 99%

Expression of thymidine phosphorylase as an effect prediction factor for uterine cervical squamous cell carcinoma after radiotherapy: an immunohistochemical study

Nakashima¹,

Nakano²,

Ametani³

et al. 2006

Int J Gynecol Cancer

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Prognoses in cases of uterine cervical squamous cell carcinoma treated with radiotherapy were investigated in association with immunohistochemical expression of an angiogenic factor, thymidine phosphorylase (TP). Forty-six cases of uterine cervical squamous cell carcinoma mainly treated with radiotherapy during 1992-2001 at our clinic were studied. All were diagnosed as stages IIB to IVA. Paraffin-embedded biopsy specimens excised before radiotherapy were stained immunohistochemically using anti-TP monoclonal antibody. The extent of staining in both tumor and interstitial cells was graded as (-), (+/-), (+), and (2+). Specimens with TP expression levels of (2+) and (+) were regarded as positively stained and those with TP expression levels of (+/-) and (-) as negatively stained. The efficacy of radiotherapy in both groups was analyzed by the Kaplan-Meier method. With tumor cells, 5-year survival rates for the positive (n= 38) and negative (n= 8) staining groups were 73.9% and 42.9%, respectively; the rate being significantly higher for the TP-positive group (log rank, P= 0.0096). Contrarily, with staining for interstitial cells, the 5-year survival rates for the positive (n= 20) and negative (n= 26) staining groups were 74.1% and 64.6%, respectively, with no significant difference (log rank, P= 0.406). The efficacy of radiotherapy in the group with positive staining of tumor cells was significantly better than in the negative staining group. Immunohistochemical expression of TP in tumor cells is suggested as a useful prognostic factor for uterine cervical squamous cell carcinomas treated with radiotherapy. Choosing therapy for individual cases by referring to factors including TP expression should contribute to an improved prognosis.

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“…Angiogenesis, the formation of new blood vessels from pre-existing vessels, is not only a critical step in embryogenesis and wound healing, but also contributes to the pathogenesis of tumor growth and chronic inflammation [ 8 , 10 , 21 , 23 , 24 ]. It is a complex process involving extensive interaction between the cells, soluble factors and extracellular matrix (ECM) components.…”

Section: Discussionmentioning

confidence: 99%

Experimentally induced puromycine aminonucleoside nephrosis (PAN) in rats: evaluation of angiogenic protein platelet-derived endothelial cell growth factor (PD-ECGF) expression in glomeruli

et al. 2012

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BackgroundIn experimentally induced puromycine aminonucleoside nephrosis (PAN) animal models, nephrotic syndrome with minimal change disease and focal and segmental sclerosis-like nephritis similar to that in human is demonstrated; however, the real mechanism of PAN is not yet elucidated. Platelet derived endothelial cell growth factor (PD-ECGF), an endothelial mitogen protein, is believed to take part in microvessel formation and in stimulation of angiogenesis and its expression has not been totally demonstrated in PAN rats yet. In this study, we aimed to examine PD-ECGF expression in acute and chronic PAN induced in rats and find out the association between its expression and the stages of angiogenesis in kidney.MethodsFor the experiment, twenty-four Male Wistar Albino rats were used and divided into four groups; control group (n = 6), pre-proteinuria group (n = 6), acute group (n = 6) and chronic group (n = 6). We compared statistically all data by One-way ANOVA Test followed by Dunn Multiple Comparison Test.ResultsProteinurea levels in control and pre-proteinuria groups were not statistically different; however, it was remarkably higher in the acute nephrosis group and significantly greater in the chronic nephrosis group than control group (p < 0.0025). In pre-proteinuria group, the serum albumin and creatinine clearances also did not significantly differ from the control group. On the other hand, in the acute and chronic nephrosis groups, serum albumin and creatinine clearances progressively decreased (p < 0.05). In our immunohistochemical studies, we showed elevated PD-ECGF expression in glomeruli of acute and chronic PAN rats. Microscopic and ultrastructural appearances of the glomeruli of acute and chronic PAN showed various sequential steps of angiogenesis, macrophages and immature capillaries with primitive lumens and apoptotic endothelial cells in the increased mesangial matrix.ConclusionsIt is reported that acute and chronic PAN progressively increase PD-ECGF expression and following induction of angiogenesis in the affected glomeruli.

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Expression of platelet-derived endothelial cell growth factor/thymidine phosphorylase in cervical intraepithelial neoplasia

Cited by 5 publications

References 0 publications

Proteomic identification of potential biomarkers for cervical squamous cell carcinoma and human papillomavirus infection

Proteomic identification of potential biomarkers for cervical squamous cell carcinoma and human papillomavirus infection

Expression of thymidine phosphorylase as an effect prediction factor for uterine cervical squamous cell carcinoma after radiotherapy: an immunohistochemical study

Experimentally induced puromycine aminonucleoside nephrosis (PAN) in rats: evaluation of angiogenic protein platelet-derived endothelial cell growth factor (PD-ECGF) expression in glomeruli

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