Alterations of the serum peptidome in renal cell carcinoma discriminating benign and malignant kidney tumors

Gianazza, Erica; Chinello, Clizia; Mainini, Veronica; Cazzaniga, Marta; Squeo, Valeria; Albo, Giancarlo; Signorini, Stefano; Pierro, Salvatore S. Di; Ferrero, Stefano; Nicolardi, Simone; Burgt, Yuri E. M. van der; Deelder, André M.; Magni, Fulvio

doi:10.1016/j.jprot.2012.07.032

Cited by 46 publications

(43 citation statements)

References 77 publications

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“…It has also been demonstrated that SDPR is an important tumor suppressor in certain cancers, including prostate cancer,20,35 breast cancer,21,36 and hepatocellular carcinoma 37. In particular, a previous study reported that SDPR was remarkably downregulated in RCC cells,22 which sparked our interest in conducting this study to investigate the functional and prognostic roles of its AS lncRNA in RCC.…”

Section: Discussionmentioning

confidence: 91%

Downregulation of lncRNA SDPR-AS is associated with poor prognosis in renal cell carcinoma

Song

Gong

et al. 2017

OTT

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Renal cell carcinoma (RCC) is a common type of kidney cancer. Normally, surgical treatment can prolong life, but only for patients with early stage tumors. However, it is difficult for early detection strategies to distinguish between benign and malignant kidney tumors. Therefore, potential biomarkers for early diagnosis and prognosis of RCC are needed. Intriguingly, mounting evidence has demonstrated that many long noncoding RNAs (lncRNAs) are strongly linked to cancers. Indeed, promising RCC-associated lncRNA biomarkers have also been identified. However, the functional and prognostic roles of the antisense (AS) serum deprivation response (SDPR) lncRNA (SDPR-AS) in RCC remain largely unknown. The aims of this study were to investigate the expression and prognostic relevance of SDPR-AS in RCC. We uncovered the downregulated expressions of both lncRNA SDPR-AS and its protein-coding gene, SDPR, in RCC tissues compared to the matched normal tissues. Furthermore, SDPR-AS and SDPR expressions were positively correlated. Overexpression and knockdown experiments suggested that SDPR-AS and SDPR were coregulated in RCC cell lines. In addition, overexpression of SDPR-AS suppressed cell migration and invasion, but not cell growth. Furthermore, expression of SDPR-AS was associated with tumor differentiation and lymphatic metastasis. Kaplan–Meier survival and log-rank tests demonstrated the association of elevated expression of SDPR-AS with increased overall survival. In conclusion, our results suggest that the SDPR-AS may serve as a prognostic biomarker and therapeutic target of RCC.

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Section: Discussionmentioning

confidence: 91%

Downregulation of lncRNA SDPR-AS is associated with poor prognosis in renal cell carcinoma

Song

Gong

et al. 2017

OTT

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“…However, it has been reported that SDPR expression is down-regulated significantly in not only breast cancer but also in cancers of kidney and prostate (15). Moreover, SDPR protein down-regulation was observed in serum from patients with malignant kidney tumors, and hence it was suggested as a possible diagnostic marker to discriminate malignant tumors from benign formations (16). Interestingly, SDPR is localized to 2q32-33, a region with a significant level of loss of heterozygosity that is associated with a high degree of recurrence in breast cancer (17,18).…”

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confidence: 99%

SDPR functions as a metastasis suppressor in breast cancer by promoting apoptosis

Öztürk

Papageorgis

Wong

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Metastatic dissemination of breast cancer cells represents a significant clinical obstacle to curative therapy. The loss of function of metastasis suppressor genes is a major rate-limiting step in breast cancer progression that prevents the formation of new colonies at distal sites. However, the discovery of new metastasis suppressor genes in breast cancer using genomic efforts has been slow, potentially due to their primary regulation by epigenetic mechanisms. Here, we report the use of model cell lines with the same genetic lineage for the identification of a novel metastasis suppressor gene, serum deprivation response (SDPR), localized to 2q32-33, a region reported to be associated with significant loss of heterozygosity in breast cancer. In silico metaanalysis of publicly available gene expression datasets suggests that the loss of expression of SDPR correlates with significantly reduced distant-metastasis–free and relapse-free survival of breast cancer patients who underwent therapy. Furthermore, we found that stable SDPR overexpression in highly metastatic breast cancer model cell lines inhibited prosurvival pathways, shifted the balance of Bcl-2 family proteins in favor of apoptosis, and decreased migration and intravasation/extravasation potential, with a corresponding drastic suppression of metastatic nodule formation in the lungs of NOD/SCID mice. Moreover, SDPR expression is silenced by promoter DNA methylation, and as such it exemplifies epigenetic regulation of metastatic breast cancer progression. These observations highlight SDPR as a potential prognostic biomarker and a target for future therapeutic applications.

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“…Meanwhile, Peptide 1984.7, a degraded derivative of thymosin beta-4-like protein 3(TMSL3), may be an significant prognostic biomarker for lung adenocarcinoma patients with BM. Gianazza et al also found an up-expressed fragment of TMSL3 at 5337.62 Da by MALDI-TOF MS serum in renal cell carcinoma (9).And the potential prognostic value of peptide 1984.7 remains to be further investigated The m/z 1969.9 Da may also serve as an significant prognostic biomarker for lung adenocarcinoma patients while m/z 1984.7 Da serve as an significant prognostic biomarker for advanced lung adenocarcinoma with BM. Few paper have investigated the prognostic value of peptide 1969.9 and 1984.7 Da.…”

Section: Discussionmentioning

confidence: 96%

Serum Proteomic Profiling of Lung Adenocarcinoma with Brain Metastasis Based on Matrix-Assisted Laser Ionization Time of Flight Mass Spectrometry Analysis

Mou¹,

Tong²,

Ren³

et al. 2014

Am. J. Biomed. Sci.

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Background: Once patients presented with brain metastasis, the prognosis is poor with shortened survival of up to 6 months, and therefore early recognition of brain metastasis may be beneficial to outcomes of patients. The present work focused on serum proteomic biomarkers that represent the status of lung adenocarcinoma especially for patients with brain metastasis. Methods: 100 serum samples including 25 from lung adenocarcinoma patients with brain metastasis，25 from lung adenocarcinoma patients without metastasis and 50 from healthy controls were analyzed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). ClinProt software and binary logistic regression method were used to develop classification model using MS spectral data. Univariate and Cox multivariate analysis were also performed to evaluate the potential prognostic value of serum peptides. Results: A series of 14 significant short peptides was detected in serum of lung adenocarcinoma patients as compared with healthy controls. Of these, a panel consisting of peptides m/z 1969.9 and 2213.4 Da had the highest diagnostic value for discriminating lung adenocarcinoma from healthy controls with a sensitivity of 91.7% and a specificity of 79.2%. The panel consisting of peptides m/z 1781.5 and 1984.7 Da had the highest diagnostic value for discriminating advanced lung adenocarcinoma with brain metastasis from patients without metastasis with a sensitivity of 84.6% and a specificity of 79.2%. Univariate and Cox multivariate analysis disclosed that peptide m/z 1969.9 Da remained an independent predictors for lung adenocarcinoma patients while peptide m/z 1984.7 Da shows favourable value on pre-warning lung adenocarcinoma patients Am. J. Biomed. Sci. 2014, 6(2), 105-116; doi: 10.5099/aj140200105 © 2014 by NWPII. All rights reserved 106 with brain metastasis after chemotherapy. Conclusion: We have completed a preliminary study to describe the serum proteomic profile of lung adenocarcinoma patients with brain metastasis, and our proteomic models may improve the diagnosis and prognosis of lung adenocarcinoma patients and helps us to better understand the pathogenesis of disease process of brain metastasis.

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Alterations of the serum peptidome in renal cell carcinoma discriminating benign and malignant kidney tumors

Cited by 46 publications

References 77 publications

Downregulation of lncRNA SDPR-AS is associated with poor prognosis in renal cell carcinoma

Downregulation of lncRNA SDPR-AS is associated with poor prognosis in renal cell carcinoma

SDPR functions as a metastasis suppressor in breast cancer by promoting apoptosis

Serum Proteomic Profiling of Lung Adenocarcinoma with Brain Metastasis Based on Matrix-Assisted Laser Ionization Time of Flight Mass Spectrometry Analysis

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