Clinicopathological features and phenotypic classification of de novo‐type colorectal carcinomas differ from those of colorectal carcinomas derived from flat adenomas

Background: A new method was developed based on the relative ranking of gene expression level, overcoming the flaw of the batch effect, and having reliable results in various studies. In the current study, we defined the two methylation sites as a pair. The methylation level in a specific sample was subject to pairwise comparison to calculate a score for each CpGs-pair. The score was defined as a CpGs-pair score. If the first immune-related CpG value was higher than the second one in a specific CpGs-pair, the output score of this immune-related CpGs-pair was 1; otherwise, the output score was 0. This study aimed to construct a new classification of Kidney Clear Cell Carcinoma (KIRC) based on DNA CpGs (methylation sites) pairs. Methods: In this study, the biomarkers of 28 kinds of immune infiltration cells and corresponding methylation sites were acquired. The methylation data were compared between KIRC and normal tissue samples, and differentially methylated sites (DMSs) were obtained. Then, DNA CpGs-pairs were obtained according to the pairs of DMSs. In total, 441 DNA CpGs-pairs were utilized to construct a classification using unsupervised clustering analysis. We also analyzed the potential mechanism and therapy of different subtypes, and validated them in a testing set. Results: The classification of KIRC contained three subgroups. The clinicopathological features were different across three subgroups. The distribution of immune cells, immune checkpoints and immune-related mechanisms were significantly different across the three clusters. The mutation and copy number variation (CNV) were also different. The clinicopathological features and potential mechanism in the testing dataset were consistent with those in the training set. Conclusions: Our findings provide a new accurate and stable classification for developing personalized treatments for the new specific subtypes.

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Phenotypic Classification of preterm Birth Among Multiparous Women: A Population-Based Cohort Study

Journal of Obstetrics and Gynaecology Canada ◽

10.1016/j.jogc.2019.03.015 ◽

2019 ◽

Vol 41 (10) ◽

pp. 1433-1443.e12

Author(s):

Siavash Maghsoudlou ◽

Joseph Beyene ◽

Zhijie Michael Yu ◽

Sarah D. McDonald

Keyword(s):

Cohort Study ◽

Preterm Birth ◽

Population Based ◽

Multiparous Women ◽

Phenotypic Classification

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Prognostic impact of β-2-microglobulin expression in colorectal cancers stratified by mismatch repair status

Journal of Clinical Pathology ◽

10.1136/jclinpath-2012-200742 ◽

2012 ◽

Vol 65 (11) ◽

pp. 996-1002 ◽

Cited By ~ 21

Author(s):

Viktor Hendrik Koelzer ◽

Kristi Baker ◽

Daniela Kassahn ◽

Daniel Baumhoer ◽

Inti Zlobec

Keyword(s):

Protein Expression ◽

Mismatch Repair ◽

Immune Cell ◽

Prognostic Significance ◽

Clinicopathological Features ◽

Prognostic Impact ◽

Mismatch Repair Status ◽

First Time ◽

Intra Class Correlation Coefficient

Backgroundβ-2-microglobulin (B2M) is essential for antigen presentation, yet may also possess proto-oncogenic properties.AimTo determine the prognostic impact of B2M in patients with mismatch repair (MMR) proficient and deficient colorectal cancer (CRC) and to investigate whether this effect on outcome is dependent on the local immune response. MethodsB2M protein expression and tumour-infiltrating immune cells (CD3, CD16, CD163, CD20, CD4, CD45RO, CD56, CD68, CD8, FoxP3, GranzymeB, iNOS, mast cell tryptase, MUM1, PD1, TIA-1) were evaluated in a well characterised tissue microarray of 408 CRCs. The predictive value for clinicopathological features and the prognostic significance of B2M expression were analysed, stratified by MMR status and the immunohistological characteristics of immune cell infiltrates. ResultsInterobserver agreement for B2M staining was high (intra-class correlation coefficient=0.91). Complete B2M loss was more frequent in MMR-deficient (19.4%) compared to MMR-proficient (7.1%) tumours (p<0.001). In MMR-deficient cases, B2M loss predicted rare local recurrence (p=0.034), infrequent nodal-positivity (p=0.035), absence of distant metastasis (p=0.048; sensitivity=100%) and a trend towards favourable survival (p=0.124) independent of immune infiltrates. No associations between B2M and clinicopathological features were observed in MMR-proficient cases.ConclusionsOur data show for the first time that absence of B2M protein expression identifies MMR-deficient cancers with a favourable clinical course and absence of metastatic disease. Validation of B2M protein expression for sub-classification of MMR-deficient CRC is recommended for future clinical trials.

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