Quantitative proteomic analysis to discover potential diagnostic markers and therapeutic targets in human renal cell carcinoma

Okamura, Noboru; Masuda, Taro; Gotoh, Akinobu; Shirakawa, Toshiro; Terao, Shuji; Kaneko, Naoki; Suganuma, Kazuki; Watanabe, Mamoru; Matsubara, Toshiya; Seto, Ryota; Matsumoto, Jun; Kawakami, Megumi; Yamamori, Motohiro; Nakamura, Tsutomu; Yagami, Tatsurou; Sakaeda, Toshiyuki; Fujisawa, Masato; Nishimura, Osamu; Okumura, Katsuhiko

doi:10.1002/pmic.200700619

Cited by 37 publications

(37 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, accumulating evidence indicates that the dipeptidase appears to do more than just perform its enzymatic activity. The protein was found to be upregulated in breast and renal cell carcinoma (9,10). Furthermore, it has been suggested that CNDP2 has distinct patterns of expression within grades in kidney cancer (19).…”

Section: Discussionmentioning

confidence: 98%

“…However, not all tumors express a low CNDP2 level, and the molecular function of CNDP2 is largely unknown. Okamura et al (9) showed through quantitative proteomic analysis that renal cell carcinoma tissues have a high level of CNDP2 expression. Tripathi et al (10) found that CNDP2 was upregulated in breast cancer tissues compared with normal breast epithelium.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Underexpressed CNDP2 Participates in Gastric Cancer Growth Inhibition through Activating the MAPK Signaling Pathway

Zhang

Miao

Xin

et al. 2013

Mol Med

View full text Add to dashboard Cite

Increasing evidence suggests that cytosolic non-specific dipeptidase 2 (CNDP2) appears to do more than just perform an enzymatic activity; it is functionally important in cancers as well. Here, we show that the expression of CNDP2 is commonly downregulated in gastric cancer tissues. The ectopic expression of CNDP2 resulted in significant inhibition of cell proliferation, induction of cell apoptosis and cell cycle arrest, and suppressed gastric tumor growth in nude mice. We further revealed that the reintroduction of CNDP2 transcriptionally upregulated p38 and activated c-Jun NH 2 -terminal kinase (JNK), whereas the loss of CNDP2 increased the phosphorylation of extracellular signal-related kinase (ERK). These results suggest that CNDP2 acts as a functional tumor suppressor in gastric cancer via activation of the mitogen-activated protein kinase (MAPK) pathway.

show abstract

Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Underexpressed CNDP2 Participates in Gastric Cancer Growth Inhibition through Activating the MAPK Signaling Pathway

Zhang

Miao

Xin

et al. 2013

Mol Med

View full text Add to dashboard Cite

show abstract

“…2 Thus, using different strategies for proteomic analysis, several different proteins expressed in RCC were identified. [3][4][5][6][7][8][9] These proteins are candidates for biomarkers belong to different families, such as the annexins, vimentin, metabolic enzymes, proteins of signal transduction pathways, growth factors, differentiation markers, tumor suppressor genes, cytoskeletal components, and stress proteins, as well as proteins involved in resistance to chemotherapy. 10 Despite these studies, existing information on renal cell carcinoma (RCC) is limited to a small number of differentially expressed proteins, which often need to be further validated by techniques such as reverse transcription polymerase chain reaction and/or immunohistochemistry using a large number of samples of RCC.…”

Section: Editorial Commentmentioning

confidence: 99%

“…5 In the present study, plasma concentrations of the RCC-related proteins were measured to evaluate whether they have potential either as primary diagnostic markers or as follow-up markers for monitoring RCC.…”

Section: Introductionmentioning

confidence: 99%

Potential tumor markers of renal cell carcinoma: α‐Enolase for postoperative follow up, and galectin‐1 and galectin‐3 for primary detection

Kaneko¹,

Gotoh

Okamura

et al. 2012

Int J of Urology

Self Cite

View full text Add to dashboard Cite

Abbreviations & Acronyms AUC = areas under the receiver operating characteristic curve CA 125 = carbohydrate antigen 125 CA 15-3 = carbohydrate antigen 15-3 CEA = carcinoembryonic antigen CNDP = cytosolic non-specific dipeptidase CT = computed tomography CV = coefficient of variation ELISA = enzyme-linked immunosorbent assay IQR = interquartile range mAb = monoclonal antibody MHC = major histocompatibility complex MRI = magnetic resonance imaging NBS = 2-nitrobenzenesulfenyl pAb = polyclonal antibody PSA = prostate-specific antigen RCC = renal cell carcinoma ROC = receiver-operating characteristic US FDA = US Food and Drug Administration Abstract: The diagnosis of renal cell carcinoma is currently based on imaging techniques, mainly because there is no blood marker available for its detection. Thus, there is still the need for the development of novel tumor markers. We examined plasma levels of eight proteins in 15 renal cell carcinoma patients before and after surgery, and in 51 healthy controls using enzyme-linked immunosorbent assay. Plasma levels of a-enolase, calnexin, galectin-1, galectin-3 and lectin mannose-binding 2 were significantly higher in renal cell carcinoma patients than in controls (P < 0.05). Among these proteins, the sensitivities for galectin-1 and galectin-3 were higher than those for calnexin and lectin mannose-binding 2 in the specificity range from 80% to 100%. A combined use of galectin-1 and galectin-3 showed 98% specificity and 47% sensitivity. In addition, the assays showed that plasma a-enolase levels decreased significantly 4 weeks after nephrectomy (P = 0.0034), and this tendency continued until 12 weeks after nephrectomy (P = 0.0156). These findings suggest that a-enolase could be used in the postoperative follow up of renal cell carcinoma patients, whereas the combined use of galectin-1 and galectin-3 might represent a useful tool for primary detection.

show abstract

“…A number of differentially expressed proteins have been described, but their implementation as accurate and stable markers allowing early detection or prognosis of disease has failed so far [32][33][34][35][36][37]. Although novel targeted therapies such as monoclonal antibodies or tyrosine kinase inhibitors have revolutionized the treatment options for RCC patients, the discovery of putative biomarkers in RCC for the determination and monitoring of therapy efficacy and immune response is still urgently required [38][39][40][41].…”

Section: Introductionmentioning

confidence: 99%

Identification and characterization of human leukocyte antigen class I ligands in renal cell carcinoma cells

Seliger¹,

Dressler²,

Massa³

et al. 2011

Proteomics Clinical Apps

View full text Add to dashboard Cite

The presentation of tumor antigen-derived peptides by human leukocyte antigen (HLA) class I surface antigens on tumor cells is a key prerequisite to trigger effective T-cell responses in cancer patients. Multiple complementary strategies like cDNA and serological expression cloning, reverse immunology and different 'ome'-based methods have been employed to identify potential T-cell targets. This report focuses on a ligandomic profiling approach leading to the identification of 49 naturally processed HLA class I peptide ligands presented on the cell surface of renal cell carcinoma (RCC) cells. The source proteins of the defined HLA ligands are classified according to their biological function and subcellular localization. Previously established cDNA microarray data of paired tissue specimen of RCC and renal epithelium assessed the transcriptional regulation for 28 source proteins. In addition, HLA-A2-restricted, peptide-specific T cells directed against a HLA ligand derived from sulfiredoxin-1 (SRXN1) were generated, which were able to recognize and lyse ligand-presenting target cells in a HLA class I-restricted manner. Furthermore, tumorinfiltrating T cells isolated from a RCC patient were also able to kill SRXN1 expressing tumor cells. Thus, this experimental strategy might be suited to define potential candidate biomarkers and novel targets for T-cell-based immunotherapies of this disease.

show abstract

Quantitative proteomic analysis to discover potential diagnostic markers and therapeutic targets in human renal cell carcinoma

Cited by 37 publications

References 33 publications

Underexpressed CNDP2 Participates in Gastric Cancer Growth Inhibition through Activating the MAPK Signaling Pathway

Underexpressed CNDP2 Participates in Gastric Cancer Growth Inhibition through Activating the MAPK Signaling Pathway

Potential tumor markers of renal cell carcinoma: α‐Enolase for postoperative follow up, and galectin‐1 and galectin‐3 for primary detection

Identification and characterization of human leukocyte antigen class I ligands in renal cell carcinoma cells

Contact Info

Product

Resources

About