Serum microRNAs as powerful cancer biomarkers

Wittmann, Jürgen; Jäck, Hans‐Martin

doi:10.1016/j.bbcan.2010.07.002

Cited by 191 publications

(176 citation statements)

References 36 publications

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“…miRNA signatures can also be identified in the peripheral circulation of cancer patients (Mitchell et al., 2008), and several tumor‐associated miRNAs have been isolated from circulating microvesicles and exosomes (Rani et al., 2011). Of note, miRNAs are relatively stable compared to mRNAs and can be profiled from paraffin‐embedded tissues and body fluids such as blood and urine (Palmero et al., 2011; Wittmann and Jack, 2010). …”

Section: Addressing Tumor Heterogeneity and Complexitymentioning

confidence: 99%

The biology of personalized cancer medicine: Facing individual complexities underlying hallmark capabilities

2012

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It is a time of great promise and expectation for the applications of knowledge about mechanisms of cancer toward more effective and enduring therapies for human disease. Conceptualizations such as the hallmarks of cancer are providing an organizing principle with which to distill and rationalize the abject complexities of cancer phenotypes and genotypes across the spectrum of the human disease. A countervailing reality, however, involves the variable and often transitory responses to most mechanism‐based targeted therapies, returning full circle to the complexity, arguing that the unique biology and genetics of a patient's tumor will in the future necessarily need to be incorporated into the decisions about optimal treatment strategies, the frontier of personalized cancer medicine. This perspective highlights considerations, metrics, and methods that may prove instrumental in charting the landscape of evaluating individual tumors so to better inform diagnosis, prognosis, and therapy. Integral to the consideration is remarkable heterogeneity and variability, evidently embedded in cancer cells, but likely also in the cell types composing the supportive and interactive stroma of the tumor microenvironment (e.g., leukocytes and fibroblasts), whose diversity in form, regulation, function, and abundance may prove to rival that of the cancer cells themselves. By comprehensively interrogating both parenchyma and stroma of patients' cancers with a suite of parametric tools, the promise of mechanism‐based therapy may truly be realized.

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Section: Addressing Tumor Heterogeneity and Complexitymentioning

confidence: 99%

The biology of personalized cancer medicine: Facing individual complexities underlying hallmark capabilities

2012

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“…[30][31][32] Indeed, in a preliminary survey of plasma samples, CRNDE-h afforded a sensitivity and specificity of 87% and 93%, respectively, for the presence of CRC (Fig. 3D), with a positive test result being returned by 13 of 15 cancer patient samples (87%) but only 1 of 15 normal controls (7%).…”

Section: Diagnostic Potential Of Crnde Transcripts and Future Workmentioning

confidence: 99%

Colorectal Neoplasia Differentially Expressed (CRNDE), a Novel Gene with Elevated Expression in Colorectal Adenomas and Adenocarcinomas

Pedersen²,

et al. 2011

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An uncharacterized gene locus (Chr16:hCG_1815491), now named colorectal neoplasia differentially expressed (gene symbol CRNDE), is activated early in colorectal neoplasia. The locus is unrelated to any known protein-coding gene. Microarray analysis of 454 tissue specimens (discovery) and 68 previously untested specimens (validation) showed elevated expression of CRNDE in >90% of colorectal adenomas and adenocarcinomas. These findings were confirmed and extended by exon microarray studies and RT-PCR assays. CRNDE transcription start sites were identified in CaCo2 and HCT116 cells by 5′-RACE. The major transcript isoforms in colorectal cancer (CRC) cell lines and colorectal tissue are CRNDE-a, -b, -d, -e, -f, -h, and -j. Except for CRNDE-d, the known CRNDE splice variants are upregulated in neoplastic colorectal tissue; expression levels for CRNDE-h alone demonstrate a sensitivity of 95% and specificity of 96% for adenoma versus normal tissue. A quantitative RT-PCR assay measuring CRNDE-h RNA levels in plasma was (with a threshold of 2 -ΔCt = 2.8) positive for 13 of 15 CRC patients (87%) but only 1 of 15 healthy individuals (7%). We conclude that individual CRNDE transcripts show promise as tissue and plasma biomarkers, potentially exhibiting high sensitivity and specificity for colorectal adenomas and cancers.

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“…Recently, a variety of potential applications of miRNAs as biomarkers has been evaluated, including early detection of tumors, tissuespecific toxicity, and pathogen detection. 24,33,41 The utilization of miRNAs as circulating biomarkers has gained great interest due to their inherent physicochemical properties. One major attribute includes the ideal stability of miRNAs in blood, which likely comes from several aspects that aid in preventing degradation: small size, association with protein complexes, and containment within exosomes and microvesicles.…”

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confidence: 99%

Evaluation of miR-122 as a Serum Biomarker for Hepatotoxicity in Investigative Rat Toxicology Studies

et al. 2015

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MicroRNAs are short noncoding RNAs involved in regulation of gene expression. Certain microRNAs, including miR-122, seem to have ideal properties as biomarkers due to good stability, high tissue specificity, and ease of detection across multiple species. Recent reports have indicated that miR-122 is a highly liver-specific marker detectable in serum after liver injury. The purpose of the current study was to assess the performance of miR-122 as a serum biomarker for hepatotoxicity in short-term (5-28 days) repeat-dose rat toxicology studies when benchmarked against routine clinical chemistry and histopathology. A total of 23 studies with multiple dose levels of experimental compounds were examined, and they included animals with or without liver injury and with various hepatic histopathologic changes. Serum miR-122 levels were quantified by reverse transcription quantitative polymerase chain reaction. Increases in circulating miR-122 levels highly correlated with serum elevations of liver enzymes, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and glutamate dehydrogenase (GLDH). Statistical analysis showed that miR-122 outperformed ALT as a biomarker for histopathologically confirmed liver toxicity and was equivalent in performance to AST and GLDH. Additionally, an increase of 4% in predictive accuracy was obtained using a multiparameter approach incorporating miR-122 with ALT, AST, and GLDH. In conclusion, serum miR-122 levels can be utilized as a biomarker of hepatotoxicity in acute and subacute rat toxicology studies, and its performance can rival or exceed those of standard enzyme biomarkers such as the liver transaminases.

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Serum microRNAs as powerful cancer biomarkers

Cited by 191 publications

References 36 publications

The biology of personalized cancer medicine: Facing individual complexities underlying hallmark capabilities

The biology of personalized cancer medicine: Facing individual complexities underlying hallmark capabilities

Colorectal Neoplasia Differentially Expressed (CRNDE), a Novel Gene with Elevated Expression in Colorectal Adenomas and Adenocarcinomas

Evaluation of miR-122 as a Serum Biomarker for Hepatotoxicity in Investigative Rat Toxicology Studies

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