Keratin 19 expression correlates with poor prognosis in breast cancer

Kabir, Nuzhat N.; Rönnstrand, Lars; Kazi, Julhash U.

doi:10.1007/s11033-014-3684-6

Cited by 39 publications

(37 citation statements)

References 18 publications

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“…By providing a targeted approach that can be rapidly applied to studying DNA at numerous regions of interest, this method helps to expand the applications of nanopore sequencing as an inexpensive alternative for generating high coverage targeted data while maintaining the advantages of long-read sequencing through directly probing the native cellular DNA. Variants passing dual-strand filter [17] Reads error-corrected using identified nanopolish variants Variants passing dual-strand filter [14] Reads error-corrected using identified nanopolish variants…”

Section: Discussionmentioning

confidence: 99%

“…Sites for methylation studies were selected by examining whole-genome nanopore methylation data from these breast cell lines 10 , searching for differentially methylated promoters between the non-tumorigenic line MCF-10A and the tumorigenic lines MCF-7 and MDA-MB-231. Candidate loci were filtered for genes where methylation status is clinically informative [16][17][18] , and compared to existing RNA-seq expression data 11 for differentially expressed genes.…”

Section: Methylation Studiesmentioning

confidence: 99%

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Targeted Nanopore Sequencing with Cas9 for studies of methylation, structural variants, and mutations

Gilpatrick

Lee

Graham

et al. 2019

Preprint

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Nanopore sequencing technology can rapidly and directly interrogate native DNA molecules. Often we are interested only in interrogating specific areas at high depth, but conventional enrichment methods have thus far proved unsuitable for long reads 1 . Existing strategies are currently limited by high input DNA requirements, low yield, short (<5kb) reads, time-intensive protocols, and/or amplification or cloning (losing base modification information). In this paper, we describe a technique utilizing the ability of Cas9 to introduce cuts at specific locations and ligating nanopore sequencing adaptors directly to those sites, a method we term 'nanopore Cas9 Targeted-Sequencing' (nCATS).We have demonstrated this using an Oxford Nanopore MinION flow cell (Capacity >10Gb+) to generate a median 165X coverage at 10 genomic loci with a median length of 18kb, representing a several hundred-fold improvement over the 2-3X coverage achieved without enrichment. We performed a pilot run on the smaller Flongle flow cell (Capacity ~1Gb), generating a median coverage of 30X at 11 genomic loci with a median length of 18kb. Using panels of guide RNAs, we show that the high coverage data from this method enables us to (1) profile DNA methylation patterns at cancer driver genes, (2) detect structural variations at known hot spots, and (3) survey for the presence of single nucleotide mutations. Together, this provides a low-cost method that can be applied even in low resource settings to directly examine cellular DNA. This technique has extensive clinical applications for assessing medically relevant genes and has the versatility to be a rapid and comprehensive diagnostic tool. We demonstrate applications of this technique by examining the well-characterized GM12878 cell line as well as three breast cell lines (MCF-10A, MCF-7, MDA-MB-231) with varying tumorigenic potential as a model for cancer. ContributionsTG and WT constructed the study. TG performed the experiments. TG, IL, and FS analyzed the data. TG, JG, ER, RB and AH and developed the method. TG and WT wrote the paper

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Section: Discussionmentioning

confidence: 99%

Section: Methylation Studiesmentioning

confidence: 99%

Targeted Nanopore Sequencing with Cas9 for studies of methylation, structural variants, and mutations

Gilpatrick

Lee

Graham

et al. 2019

Preprint

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“…The pan-cytokeratin antibody has been mainly exploited in prognostic studies of circulating and disseminated epithelial tumor cells, particularly in assessing sentinel lymph node biopsies in breast cancer (11). Other approaches comprised prognostic investigations of tumor immunostaining by cytokeratin panels (12) or single keratins (13). …”

Section: Introductionmentioning

confidence: 99%

The Pan-Cytokeratin Staining Intensity and Fractal Computational Analysis of Breast Tumor Malignant Growth Patterns Prognosticate the Occurrence of Distant Metastasis

Rajković

Plataniotis

et al. 2018

Front. Oncol.

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Improved prognosis of breast cancer outcome could prolong patient survival by reliable identification of patients at high risk of metastasis occurrence which could benefit from more aggressive treatments. Based on such clinical need, we prognostically evaluated the malignant cells in breast tumors, as the obvious potential source of unexploited prognostic information. The patient group was homogeneous, without any systemic treatments or lymph node spread, with smaller tumor size (pT1/2) and a long follow-up. Epithelial cells were labeled with AE1/AE3 pan-cytokeratin antibody cocktail and comprehensively analyzed. Monofractal and multifractal analyses were applied for quantification of distribution, shape, complexity and texture of malignant cell clusters, while mean pixel intensity and total area were measures of the pan-cytokeratin immunostaining intensity. The results surprisingly indicate that simple binary images and monofractal analysis provided better prognostic information then grayscale images and multifractal analysis. The key findings were that shapes and distribution of malignant cell clusters (by binary fractal dimension; AUC = 0.29), their contour shapes (by outline fractal dimension; AUC = 0.31) and intensity of the pan-cytokeratin immunostaining (by mean pixel intensity; AUC = 0.30) offered significant performance in metastasis risk prognostication. The results reveal an association between the lower pan-cytokeratin staining intensity and the high metastasis risk. Another interesting result was that multivariate analysis could confirm the prognostic independence only for fractal but not for immunostaining intensity features. The obtained results reveal several novel and unexpected findings highlighting the independent prognostic efficacy of malignant cell cluster distribution and contour shapes in breast tumors.

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“…This pattern is indicative of elevated transcriptional levels and synthesis of proteins participating in cancer progression. This pattern was detected for all of the genes analyzed [8][9][10][11][12] with the exception of SNX10, which showed an inverse correlation between protein and gene expression.…”

Section: Discussionmentioning

confidence: 78%

Downregulation of sorting nexin 10 is associated with overexpression of miR-30d during liver cancer progression in rats

et al. 2017

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As of 2012, liver cancer was the second leading cause of death worldwide, and hepatocellular carcinoma is the most common primary cancer of the liver. The identification of molecules that might be molecular markers or therapeutic targets is urgently needed to improve clinical management. Based on a microarray analysis performed in our laboratory, we selected six genes-namely, ANXA2, DYNLT1, PFKP, PLA2G7, KRT19, and SNX10-as candidates for validation as tumor markers of liver cancer in a rat model. Their patterns of overexpression in preneoplastic lesions and established tumors at 10 different time points between 24 h and 18 months were analyzed to identify putative tumor markers for further studies. We validated the microarray results by quantitative reverse transcription polymerase chain reaction, which revealed high transcriptional expression for five of the genes, consistent with their high protein expression during cancer progression reported in the literature. However, studies of the association of sorting nexin 10 with different types of cancer are limited, prompting further study. The characterization of sorting nexin 10 in preneoplastic lesions and established tumors revealed messenger RNA overexpression and a simultaneous decrease in sorting nexin 10 protein expression. A group of microRNAs related to sorting nexin 10 messenger RNA were selected based on a data analysis conducted using miRDB and microrna.org. An analysis of the expression of these microRNAs revealed an increase in the transcription of microRNA-30d whenever the sorting nexin 10 protein was downregulated. These results suggest that sorting nexin 10 is a potential liver cancer marker exhibiting characteristics of a putative suppressor protein that is likely regulated by microRNA-30d.

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Keratin 19 expression correlates with poor prognosis in breast cancer

Cited by 39 publications

References 18 publications

Targeted Nanopore Sequencing with Cas9 for studies of methylation, structural variants, and mutations

Targeted Nanopore Sequencing with Cas9 for studies of methylation, structural variants, and mutations

The Pan-Cytokeratin Staining Intensity and Fractal Computational Analysis of Breast Tumor Malignant Growth Patterns Prognosticate the Occurrence of Distant Metastasis

Downregulation of sorting nexin 10 is associated with overexpression of miR-30d during liver cancer progression in rats

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