T-Cell Receptor Repertoire Characteristics Associated with Prognostic Significance in High-Grade Serous Ovarian Carcinoma.

High-grade serous ovarian carcinoma (HGSOC) is a fatal gynecological malignancy. Somatic recombination occurring during T-cell receptor (TCR) development results in TCR diversity, and the TCR repertoire, thus produced, is associated with immune response. This study analyzed the difference in the TCR repertoire and their prognostic significance in 51 patients with HGSOC. The patient's clinical characteristics, gene expression pattern, TCR clonotypes, and degree of tumor-infiltrating leukocytes (TILs) were analyzed, and the patients were divided into groups depending on their recurrence pattern, tumor-infiltrating leukocyte (TIL) score, and homologous recombinant repair pathway deficiency (HRD)-associated mutations. The TCR repertoire was low in patients with recurrence and showed the expansion of eight TCR segments. Interestingly, a few genes correlated with the TCRs also showed a difference in expression according to the prognosis. Among them, seven genes were related to immune responses and KIAA1199 was up-regulated in ovarian cancer. Our study shows that the differences in the TCR repertoire in patients with ovarian cancer and their associated immune pathways could affect the prognosis of HGSOC.

Combined Model-Based Prediction for Non-Invasive Prenatal Screening.

The risk of chromosomal abnormalities in the child increases with increasing maternal age. Although non-invasive prenatal testing (NIPT) is a safe and effective prenatal screening method, the accuracy of the test results needs to be improved owing to various testing conditions. We attempted to achieve a more accurate and robust prediction of chromosomal abnormalities by combining multiple methods. Here, three different methods, namely standard Z-score, normalized chromosome value, and within-sample reference bin, were used for 1698 reference and 109 test samples of whole-genome sequencing. The logistic regression model combining the three methods achieved a higher accuracy than any single method. In conclusion, the proposed method offers a promising approach for increasing the reliability of NIPT.

Reduced diversity of intestinal T-cell receptor repertoire in patients with Crohn's disease.

Background: The intestinal microenvironment directly determines the human T-cell receptor (TCR) repertoire. Despite its extreme diversity, TCR repertoire analysis may provide a better understanding of the immune system in patients with inflammatory bowel disease. Methods: To investigate TCR repertoires in the intestinal mucosa, RNA sequencing was performed for inflamed and non-inflamed intestinal mucosa samples obtained from 13 patients with Crohn's disease (CD) and healthy mucosa from nine non-IBD controls. Results: The gene expression frequency of the TCR repertoire showed a clear separation between inflamed mucosa of patients with CD and healthy mucosa of non-IBD controls in the hierarchical clustering heatmap. The richness of TCR repertoires measured by the Chao1 index did not show a significant difference among groups, whereas diversity measured by the D50 diversity index was decreased in the inflamed mucosa of CD patients. Rare/small TCR clonotypes occupied a large proportion of TCR repertoires in healthy mucosa of controls, whereas expanded clonotypes were common in inflamed mucosa of patients with CD. Segment usages of TRAV2, TRAV22, TRAV40, TRJ14, TRAJ51, TRBV1, TRBV21.1, and TRBJ1.5 were significantly decreased in CD patients. KEGG enrichment analysis identified the enrichment of several KEGG pathways, including inflammatory bowel disease (p = 0.0012), Th1 and Th2 cell differentiation (p = 0.0011), and intestinal immune network for IgA production (p = 0.0468). Conclusions: The diversity of the TCR repertoire is reduced in inflamed mucosa of CD patients, which might contribute to intestinal inflammation.