Identification of true differentially expressed mRNAs in a pair of human bladder transitional cell carcinomas using an improved differential display procedure

Gromova, Irina; Gromov, Pavel; Celis, Julio E.

doi:10.1002/(sici)1522-2683(19990201)20:2<241::aid-elps241>3.0.co;2-a

Cited by 39 publications

(15 citation statements)

References 26 publications

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“…CD24 is expressed in a large variety of human tissues: physiologically, in developing or regenerating tissues (Figarella-Branger et al, 1993;Shirasawa et al, 1993;Poncet et al, 1996;Cram et al, 1999) and a few mature cell types such as, for example, granulocytes, keratinocytes (Redondo et al, 1998) and renal tubules (Droz et al, 1990). Pathologically, CD24 has been described in B-cell neoplasia (Pirucello and Lang, 1990;Raife et al, 1994;Lavabre-Bertrand et al, 1994), renal cell carcinoma (Droz et al, 1990), small cell lung cancer (Jackson et al, 1992), nasopharyngeal carcinoma (Karran et al, 1995), hepatocellular carcinoma (Huang and Hsu, 1995), bladder carcinoma (Gromova et al, 1999), glioma (Senner et al, 1999), breast cancer (Fogel et al, 1999;Liu and Vadgama, 2000) and ovarian cancer (Welsh et al, 2001;Kristiansen et al, 2002). This ubiquitous expression obviously excludes a diagnostic use of CD24 as a specific marker for NSCLC or any other tumour type.…”

Section: Discussionmentioning

confidence: 99%

“…It is a small heavily glycosylated mucin-like glycosyl-phosphatidylinositol(GPI)-linked cell surface protein (Pirruccello and Le Bien, 1986;Fischer et al, 1990;Akashi et al, 1994), which is physiologically expressed not only in developing (Shirasawa et al, 1993;Poncet et al, 1996;Cram et al, 1999) or regenerating (Figarella-Branger et al, 1993) tissue, but also in granulocytes, pre-B-cells, keratinocytes (Redondo et al, 1998) and renal tubules (Droz et al, 1990). In neoplasia, CD24 expression has been described not only in haematologic malignancies (Pirruccello and Lang, 1990;Raife et al, 1994;LavabreBertrand et al, 1994), but also in a large variety of solid tumours, for example, renal cell carcinoma (Droz et al, 1990), small cell lung cancer (Jackson et al, 1992), nasopharyngeal carcinoma (Karran et al, 1995), hepatocellular carcinoma (Huang and Hsu, 1995), bladder carcinoma (Gromova et al, 1999), glioma (Senner et al, 1999), breast cancer (Fogel et al, 1999;Yang et al, 1999;Liu and Vadgama, 2000) and ovarian cancer (Welsh et al, 2001;Kristiansen et al, 2002). CD24 is a ligand of P-selectin (Sammar et al, 1994), an adhesion receptor on activated endothelial cells and platelets, and could thus contribute to the metastasising capacities of CD24-expressing tumour cells (Aigner et al, 1995(Aigner et al, , 1997(Aigner et al, , 1998Friederichs et al, 2000).…”

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CD24 is an independent prognostic marker of survival in nonsmall cell lung cancer patients

et al. 2003

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Originally identified as a B-cell marker, expression of the cell surface molecule CD24 has meanwhile been observed in a variety of human malignancies. It appears to function as a ligand of P-Selectin, an adhesion molecule that is present in activated platelets and endothelial cells. We aimed to determine the rate of CD24 expression in our nonsmall cell lung cancer (NSCLC) collection and to clarify its correlation with clinicopathological parameters including patients' survival. A total of 89 NSCLC were analysed immunohistochemically using a monoclonal CD24 antibody (clone 24C02) and a standard detection system (LSAB, DAKO) on NSCLC tissue microarrays (TMA). The staining was semiquantitatively scored (0, 1+, 2+, 3+) and grouped into high (2+, 3+)-and low (0, 1+)-level expression for statistical analysis. A high level of CD24 expression was observed in 45% of the cases, preferentially adenocarcinomas. Patients whose tumours had a high CD24 expression showed a significantly shorter median survival time of 23 months vs 38 months (P ¼ 0.033, log-rank test). Similarly tumour, grading, nodal status and clinical stage were significant prognostic markers in univariate survival analysis. Importantly, in the Cox regression-based multivariate analysis, CD24 expression (P ¼ 0.025) together with tumour stage (P ¼ 0.006) and grade (P ¼ 0.011) proved to be independent prognostic parameters. We hypothesise that the decreased survival of NSCLC patients with strongly CD24-positive tumours is related to an enhanced propensity of haematogenous metastasis formation, which might be P-Selectin mediated.

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CD24 is an independent prognostic marker of survival in nonsmall cell lung cancer patients

et al. 2003

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“…The HOX gene network, the most repeat-poor regions of the human genome (Lander et al, 2001), is also expressed in normal adult human organs (Cillo, 1994-95). Hox and homeobox genes appear to regulate normal development, cell differentiation (Magli et al, 1991;Cantile et al, 2003b) and control other cellular processes, as proven by the recent description of congenital (Mortlock and Innis, 1997), somatic (Nakamura et al, 1996), metabolic (Ferber et al, 2000) and neoplastic alterations (Gromova et al, 1999;Cillo et al, 2001;Abate-Shen, 2002) involving these genes.…”

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confidence: 99%

Hyperexpression of locus C genes in the HOX network is strongly associated in vivo with human bladder transitional cell carcinomas

et al. 2003

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Bladder carcinogenesis remains unclear despite the identification of chemical, environmental and genetic factors. It has recently been reported that the chromosomal region 12q13-q15, containing crucial cancer genes such as MDM2, CDK4 and GLI, is amplified in bladder cancer. In the same region are also located the genes of the locus HOX C, flanked by keratin genes whose protein product may be a prognostic marker of bladder cancer. The HOX genes constitute a network of transcription factors controlling embryonal development and play an important role in crucial adult eukaryotic cell functions. The molecular organization of this 39-gene network is unique in the genome and probably acts by regulating phenotypical cell identity. We have analysed the expression of the whole HOX gene network in pairs of normaltumour bladder and in tumoral biopsies. Comparison between normal urothelium and bladder tumour has identified dramatic variations of expression in a block of three genes (HOX C4, HOX C5 and HOX C6) localized in the HOX C locus on the chromosome 12q13 and in the paralogous group 11 HOX genes, involved during normal development in the formation of the urogenital system. These data suggest a key involvement of the HOX gene network, and especially the locus C, in bladder cancer.

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“…Toward this aim, we have examined the protein expression profiles of more than 1,000 samples (benign as well as tumors of various histopathological grades and stages) using gel-based proteomics, and we have identified a number of potentially useful biomarkers, such as adipocyte-type fatty acid-binding protein (A-FABP), 14-3-3 protein isoform , psoriasin (S100A7), GST Mu, 15-hydroxyprostaglandin dehydrogenase, tropomyosin 4, disulfide isomerase precursor (ERP60), homeobox protein (HOX-1.3), keratins 8 and 13, MRP-14, CD24, and the cytochrome oxidase III subunit among others (5)(6)(7)(8)(9)(10)(11)(12), whose expression strongly correlates with a particular step of bladder cancer progression.…”

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Bladder Cancer-associated Protein, a Potential Prognostic Biomarker in Human Bladder Cancer

Moreira

Ohlsson

Gromov

et al. 2010

Molecular & Cellular Proteomics

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It is becoming increasingly clear that no single marker will have the sensitivity and specificity necessary to be used on its own for diagnosis/prognosis of tumors. Interpatient and intratumor heterogeneity provides overwhelming odds against the existence of such an ideal marker. With this in mind, our laboratory has been applying a long term systematic approach to identify multiple biomarkers that can be used for clinical purposes. As a result of these studies, we have identified and reported several candidate biomarker proteins that are deregulated in bladder cancer. Following the conceptual biomarker development phases proposed by the Early Detection Research Network, we have taken some of the most promising candidate proteins into postdiscovery validation studies, and here we report on the characterization of one such biomarker, the bladder cancer-associated protein (BLCAP), formerly termed Bc10. To characterize BLCAP protein expression and cellular localization patterns in benign bladder urothelium and urothelial carcinomas (UCs), we used two independent sets of samples from different patient cohorts: a reference set consisting of 120 bladder specimens (formalin-fixed as well as frozen biopsies) and a validation set consisting of 2,108 retrospectively collected UCs with long term clinical followup. We could categorize the UCs examined into four groups based on levels of expression and subcellular localization of BLCAP protein and showed that loss of BLCAP expression is associated with tumor progression. The results indicated that increased expression of this protein confers an adverse patient outcome, suggesting that categorization of staining patterns for this protein may have prognostic value. Finally, we applied a combinatorial two-marker discriminator using BLCAP and adipocyte-type fatty acid-binding protein, another UC biomarker previously reported by us, and found that the combination of the two markers correlated more closely with grade and/or stage of disease than the individual markers. The implications of these results in biomarker discovery are discussed.Molecular & Cellular Proteomics 9:161-177, 2010.

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Identification of true differentially expressed mRNAs in a pair of human bladder transitional cell carcinomas using an improved differential display procedure

Cited by 39 publications

References 26 publications

CD24 is an independent prognostic marker of survival in nonsmall cell lung cancer patients

CD24 is an independent prognostic marker of survival in nonsmall cell lung cancer patients

Hyperexpression of locus C genes in the HOX network is strongly associated in vivo with human bladder transitional cell carcinomas

Bladder Cancer-associated Protein, a Potential Prognostic Biomarker in Human Bladder Cancer

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