Increased nucleophosmin expression is a strong predictor of recurrence and prognosis in patients with N0M0 upper tract urothelial carcinoma undergoing radical nephroureterectomy

Sawazaki, Harutake; Ito, Keiichi; Kuroda, Kenji; Sato, Akinori; Asakuma, Junichi; Horiguchi, Akio; Seguchi, Kazuyoshi; Asano, Tomohiko

doi:10.1007/s00345-016-1977-1

Cited by 7 publications

(7 citation statements)

References 22 publications

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“…Of these 442 proteins, 102 ( t ‐test <0·05) and 20 (B‐H adjusted t ‐test P < 0·05) proteins were differentially expressed between the two patient groups (all 102 are listed in Table SII) (Fig ). Sixty‐five proteins were overexpressed in the REF/REL group and several of these proteins (Elongation factor 1‐beta, 14‐3‐3 protein gamma, nucleophosmin 1, RAP1B, Heat shock protein 60 and IMP dehydrogenase 2) have previously been described as negative prognostic factors or involved in drug resistance in other malignancies (De Bortoli et al , ; Li et al , ; Raungrut et al , ; Zhou et al , ; Yang et al , ; Sawazaki et al , ). Two proteins overexpressed in the REF/REL group have been reported as a negative prognostic marker or associated with multidrug resistance in DLBCL: Y‐box protein 1 (Miao et al , ) and pontin/RuvBL1 protein (Nishiu et al , ).…”

Section: Resultsmentioning

confidence: 99%

Expression of ribosomal and actin network proteins and immunochemotherapy resistance in diffuse large B cell lymphoma patients

et al. 2018

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Diffuse large B cell lymphoma (DLBCL) patients with early relapse or refractory disease have a very poor outcome. Immunochemotherapy resistance will probably, also in the era of targeted drugs, remain the major cause of treatment failure. We used proteomic mass spectrometry to analyse the global protein expression of micro-dissected formalin-fixed paraffin-embedded tumour tissues from 97 DLBCL patients: 44 with primary refractory disease or relapse within 1 year from diagnosis (REF/REL), and 53 who were progression-free more than 5 years after diagnosis (CURED). We identified 2127 proteins: 442 were found in all patients and 102 were differentially expressed. Sixty-five proteins were overexpressed in REF/REL patients, of which 46 were ribosomal proteins (RPs) compared with 2 of the 37 overexpressed proteins in CURED patients (P = 7·6 × 10 ). Twenty of 37 overexpressed proteins in CURED patients were associated with actin regulation, compared with 1 of 65 in REF/REL patients (P = 1·4 × 10 ). Immunohistochemical staining showed higher expression of RPS5 and RPL17 in REF/REL patients while MARCKS-like protein, belonging to the actin network, was more highly expressed in CURED patients. Even though functional studies aimed at individual proteins and protein interactions to evaluate potential clinical effect are needed, our findings suggest new mechanisms behind immunochemotherapy resistance in DLBCL.

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Section: Resultsmentioning

confidence: 99%

Expression of ribosomal and actin network proteins and immunochemotherapy resistance in diffuse large B cell lymphoma patients

et al. 2018

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“…[20][21][22] Sawazaki et al reported that nucleophosmin is strongly associated with the recurrence and prognosis of urothelial carcinoma patients with radical nephroureterectomy. 23 Chen et al revealed that NPM1 inhibits apoptosis through its effects on Akt activity in breast cancer. 24 However, the upstream molecular mechanisms through which NPM1 promotes cancer progression remain unclear.…”

Section: Discussionmentioning

confidence: 99%

<p>Aurora-B Promotes Osteosarcoma Cell Growth and Metastasis Through Activation of the NPM1/ERK/NF-κβ/MMPs Axis</p>

Song

Zhou

Peng

et al. 2020

CMAR

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Osteosarcoma (OS) is the most common primary malignant tumor of the bone in young adolescents and children. We explored the underlying mechanism of Aurora-B in promoting OS cell proliferation and metastasis. Patient and Methods: Bioinformatics was employed to predict the substrate of Aurora-B. IHC and Western blot were used to confirm the correlation between Aurora-B and NPM1. ERK/NF-κβ pathway-related proteins were detected by Western blot and immunofluorescence (IF). CCK8, wound healing, transwell, and Tunel assays were used to identify the cell proliferation, migration and apoptosis potential. Spontaneous metastasis xenografts were established to confirm the role of Aurora-B and NPM1. Results: Aurora-B promotes NPM1 phosphorylation on Ser125. The phosphorylation of NPM1 Ser125 induced by Aurora-B activates the ERK/NF-κβ signaling. Further study revealed that Aurora-B promotes proliferation, migration and inhibits apoptosis via phosphorylating NPM1 in vitro and in vivo. Conclusion: Aurora-B promotes OS malignancy via phosphorylating NPM1 Ser125 and activating ERK/NF-κβ signaling.

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“…NPM expression predicts recurrence and survival in upper tract urothelial carcinoma. High NPM expression significantly correlates with tumor location [ 52 ]. NPM is a multifunctional oligomeric phosphoprotein and is encoded by the NPM1 gene [ 53 , 54 ].…”

Section: Discussionmentioning

confidence: 99%

Differential expression of NPM, GSTA3, and GNMT in mouse liver following long-term in vivo irradiation by means of uranium tailings

Liang

et al. 2018

Bioscience Reports

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Uranium tailings (UT) are formed as a byproduct of uranium mining and are of potential risk to living organisms. In the present study, we sought to identify potential biomarkers associated with chronic exposure to low dose rate γ radiation originating from UT. We exposed C57BL/6J mice to 30, 100, or 250 μGy/h of gamma radiation originating from UT samples. Nine animals were included in each treatment group. We observed that the liver central vein was significantly enlarged in mice exposed to dose rates of 100 and 250 μGy/h, when compared with nonirradiated controls. Using proteomic techniques, we identified 18 proteins that were differentially expressed (by a factor of at least 2.5-fold) in exposed animals, when compared with controls. We chose glycine N-methyltransferase (GNMT), glutathione S-transferase A3 (GSTA3), and nucleophosmin (NPM) for further investigations. Our data showed that GNMT (at 100 and 250 μGy/h) and NPM (at 250 μGy/h) were up-regulated, and GSTA3 was down-regulated in all of the irradiated groups, indicating that their expression is modulated by chronic gamma radiation exposure. GNMT, GSTA3, and NPM may therefore prove useful as biomarkers of gamma radiation exposure associated with UT. The mechanisms underlying those changes need to be further studied.

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Increased nucleophosmin expression is a strong predictor of recurrence and prognosis in patients with N0M0 upper tract urothelial carcinoma undergoing radical nephroureterectomy

Cited by 7 publications

References 22 publications

Expression of ribosomal and actin network proteins and immunochemotherapy resistance in diffuse large B cell lymphoma patients

Expression of ribosomal and actin network proteins and immunochemotherapy resistance in diffuse large B cell lymphoma patients

<p>Aurora-B Promotes Osteosarcoma Cell Growth and Metastasis Through Activation of the NPM1/ERK/NF-κβ/MMPs Axis</p>

Differential expression of NPM, GSTA3, and GNMT in mouse liver following long-term in vivo irradiation by means of uranium tailings

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