CD74: a new prognostic factor for patients with malignant pleural mesothelioma

Otterstrom, C; Soltermann, Alex; Opitz, Isabelle; Felley‐Bosco, Emanuela; Weder, Walter; Stahel, Rolf A.; Triponez, Frédéric; Robert, John; Serre‐Beinier, Véronique

doi:10.1038/bjc.2014.117

Cited by 31 publications

(28 citation statements)

References 53 publications

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“…Irrespective of the mechanism(s) involved, CD74 now meets the criteria as a validated marker of improved prognosis in stage III melanoma patients. Similar findings that high expression of CD74 is an independent prognostic factor for OS were recently reported in mesothelioma (27). …”

Section: Discussionsupporting

confidence: 90%

Inflammatory Marker Testing Identifies CD74 Expression in Melanoma Tumor Cells, and Its Expression Associates with Favorable Survival for Stage III Melanoma

Ekmekçioglu

Davies

Tanese

et al. 2016

Clinical Cancer Research

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Purpose Inflammatory marker expression in stage III melanoma tumors was evaluated for association with outcome, using two independent cohorts of stage III melanoma patients’ tumor tissues. Experimental Design Fifteen markers of interest were selected for analysis, and their expression in melanoma tissues was determined by immunohistochemistry. Proteins associating with either overall survival (OS) or relapse-free survival (RFS) in the retrospective discovery tissue microarray (TMA) (n = 158) were subsequently evaluated in an independent validation TMA (n = 114). Cox proportional hazards regression models were used to assess the association between survival parameters and covariates, the Kaplan-Meier method to estimate the distribution of survival, and the log-rank test to compare distributions. Results Expression of CD74 on melanoma cells was unique, and in the discovery TMA it associated with favorable patient outcome (OS: HR, 0.53, P = 0.01 and RFS: HR, 0.56; P = 0.01). The validation dataset confirmed the CD74 prognostic significance and revealed that the absence of MIF and iNOS was also associated with poor survival parameters. Consistent with the protein observation, tumor CD74 mRNA expression also correlated positively (p = 0.003) with OS in the melanoma TCGA dataset. Conclusions Our data validate CD74 as a useful prognostic tumor cell protein marker associated with favorable RFS and OS in stage III melanoma. Low or negative expression of MIF in both TMAs, and of iNOS in the validation set also provided useful prognostic data. A disease-specific investigation of CD74’s functional significance is warranted, and other markers appear intriguing to pursue.

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Section: Discussionsupporting

confidence: 90%

Inflammatory Marker Testing Identifies CD74 Expression in Melanoma Tumor Cells, and Its Expression Associates with Favorable Survival for Stage III Melanoma

Ekmekçioglu

Davies

Tanese

et al. 2016

Clinical Cancer Research

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“…CD74, a transmembrane glycoprotein, associates with the major histocompatibility complex (MHC) Class II and plays important roles in the intratumoral immune response [27–29]. CD74 was overexpressed in thyroid malignancy, malignant pleural mesothelioma, and head and neck squamous cell carcinomas, and it is associated with advanced tumor stage [30–32]. Shakib et al [33] found that both CD44 and CD74 proteins were significantly overexpressed in oral squamous cell carcinoma (OSCC) patients.…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of CD44 in human colon cancer and gastric cancer: Evidence from bioinformatic analyses

2016

Oncotarget

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CD44 is a well-recognized stem cell biomarker expressed in colon and gastric cancer. In order to identify whether CD44 mRNA could be used as a prognostic marker in colon and gastric cancer, bioinformatic analyses were used in this study. cBioPortal analysis and COSMIC analysis were used to explore the CD44 mutation. CD44 mRNA levels were evaluated by using SAGE Genie tools and Oncomine analysis. Kaplan-Meier Plotter was performed to identify the prognostic roles of CD44 mRNA in these two cancers. In this study, first, we found that low alteration frequency of CD44 mRNA in colon and gastric cancer. Second, the high CD44 mRNA level was found in colon and gastric cancer, and it correlated with a benign survival rate in gastric cancer. Third, CD4 and CD74 may be used as markers to predict the prognosis of colon and gastric cancer. However, the deep mechanism(s) of these results remains unclear, further studies have to be performed in the future.

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“…Calretinin, a Ca 2+ binding protein, is a diagnostic and prognostic marker for mesothelioma (Kao et al, 2011; Linton et al, 2014; Ordóñez, 2014; Otterstrom et al, 2014). So far, molecular mechanisms driving calretinin expression in mesothelioma remain largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Posttranscriptional Regulation Controls Calretinin Expression in Malignant Pleural Mesothelioma

et al. 2017

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Calretinin (CALB2) is a diagnostic and prognostic marker in malignant pleural mesothelioma (MPM). We previously reported that calretinin expression is regulated at the mRNA level. The presence of a medium-sized (573 nucleotide) 3′ untranslated region (3′UTR) predicted to contain binding sites for miR-30a/b/c/d/e and miR-9 as well as an adenine/uridine-rich element (ARE) in all three transcripts arising from the CALB2 gene, suggests that calretinin expression is regulated via posttranscriptional mechanisms. Our aim was to investigate the role of the CALB2-3′UTR in the posttranscriptional regulation of calretinin expression in MPM. CALB2-3′UTR was inserted downstream of the luciferase reporter gene using pmiRGLO vector and reporter expression was determined after transfection into MPM cells. Targeted mutagenesis was used to generate variants harboring mutated miR-30 family and ARE binding sites. Electrophoretic mobility shift assay was used to test for the presence of ARE binding proteins. CALB2-3′UTR significantly decreased luciferase activity in MPM cells. Analysis of mutation in the ARE site revealed a further destabilization of the reporter and human antigen R (HuR) binding to the ARE sequence was detected. The mutation of two miR-30 binding sites abolished CALB2-3′UTR destabilization effect; a transient delivery of miR-30e-5p mimics or anti-miR into MPM cells resulted in a significant decrease/increase of the luciferase reporter expression and calretinin protein, respectively. Moreover, overexpression of CALB2-3′UTR quenched the effect of miR-30e-5p mimics on calretinin protein levels, possibly by sequestering the mimics, thereby suggesting a competitive endogenous RNA network. Finally, by data mining we observed that expression of miR-30e-5p was negatively correlated with the calretinin expression in a cohort of MPM patient samples. Our data show the role of (1) adenine-uridine (AU)-binding proteins in calretinin stabilization and (2) miR-30e-5p in the posttranscriptional negative regulation of calretinin expression via interaction with its 3′UTR. Furthermore, our study demonstrates a possible physiological role of calretinin’s alternatively spliced transcripts.

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CD74: a new prognostic factor for patients with malignant pleural mesothelioma

Cited by 31 publications

References 53 publications

Inflammatory Marker Testing Identifies CD74 Expression in Melanoma Tumor Cells, and Its Expression Associates with Favorable Survival for Stage III Melanoma

Inflammatory Marker Testing Identifies CD74 Expression in Melanoma Tumor Cells, and Its Expression Associates with Favorable Survival for Stage III Melanoma

Prognostic significance of CD44 in human colon cancer and gastric cancer: Evidence from bioinformatic analyses

Posttranscriptional Regulation Controls Calretinin Expression in Malignant Pleural Mesothelioma

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