BRCA1 mRNA expression modifies the effect of T cell activation score on patient survival in breast cancer.

BACKGROUND: Effector CD8+ T cell activation and its cytotoxic function to eradicate tumor cells depend on the T cell recognition of tumor neoantigens, and are positively associated with improved survival in breast cancer. Tumor suppressor BRCA1 and cell cycle regulator CCND1 play a critical role in maintaining genome integrity and tumorigenesis, respectively. However, it is still unclear how BRCA1 and CCND1 expression levels affect the effect of T cell activation on breast cancer patient survival. METHODS: The interactions between T cell activation status and either BRCA1 or CCND1 expression were evaluated using Kaplan-Meier survival curves and multivariate Cox regression models in a public dataset with 1088 breast cancer patients. RESULTS: Among the patients with low BRCA1 or CCND1 expression, the Activation group showed better overall survival than the Exhaustion group. Adjusted hazards ratios were 0.43 (95% CI: 0.20-0.93) in patients with a low BRCA1 level, and 0.39 (95% CI: 0.19-0.81) in patients with a low CCND1 level, respectively. There was a significant trend in both subgroups (p-trend = 0.011 in the low BRCA1 group, and p-trend = 0.009 in the low CCND1 group). In contrast, there is no significant association in patients with either high BRCA1 or high CCND1 levels. There is a significant interaction between T cell activation status and BRCA1 level (p = 0.009), but not between T cell activation status and CCND1 level (p = 0.135). CONCLUSIONS: BRCA1 expression modified the effect of T cell activation status on patient survival in breast cancer, suggesting that the existence of neoantigens and the enhancement of neoantigen presentation in combination with immune checkpoint blockade may have synergistic effects on patient outcome.

Association of tRNA methyltransferase NSUN2/IGF-II molecular signature with ovarian cancer survival.

AIM: To investigate the association between NSUN2/IGF-II signature and ovarian cancer survival. METHODS: Using a publicly accessible dataset of RNA sequencing and clinical follow-up data, we performed Classification and Regression Tree and survival analyses. RESULTS: Patients with NSUN2 high IGF-II low had significantly superior overall and disease progression-free survival, followed by NSUN2 low IGF-II low, NSUN2 high IGF-II high and NSUN2 low IGF-II high (p < 0.0001 for overall, p = 0.0024 for progression-free survival, respectively). The associations of NSUN2/IGF-II signature with the risks of death and relapse remained significant in multivariate Cox regression models. Random-effects meta-analyses show the upregulated NSUN2 and IGF-II expression in ovarian cancer versus normal tissues. CONCLUSION: The NSUN2/IGF-II signature associates with heterogeneous outcome and may have clinical implications in managing ovarian cancer.

A Circulating Exosome RNA Signature Is a Potential Diagnostic Marker for Pancreatic Cancer, a Systematic Study.

Several exosome proteins, miRNAs and KRAS mutations have been investigated in the hope of carrying out the early detection of pancreatic cancer with high sensitivity and specificity, but they have proven to be insufficient. Exosome RNAs, however, have not been extensively evaluated in the diagnosis of pancreatic cancer. The purpose of this study was to investigate the potential of circulating exosome RNAs in pancreatic cancer detection. By retrieving RNA-seq data from publicly accessed databases, differential expression and random-effects meta-analyses were performed. The results showed that pancreatic cancer had a distinct circulating exosome RNA signature in healthy individuals, and that the top 10 candidate exosome RNAs could distinguish patients from healthy individuals with an area under the curve (AUC) of 1.0. Three (HIST2H2AA3, LUZP6 and HLA-DRA) of the 10 genes in exosomes had similar differential patterns to those in tumor tissues based on RNA-seq data. In the validation dataset, the levels of these three genes in exosomes displayed good performance in distinguishing cancer from both chronic pancreatitis (AUC = 0.815) and healthy controls (AUC = 0.8558), whereas a slight difference existed between chronic pancreatitis and healthy controls (AUC = 0.586). Of the three genes, the level of HIST2H2AA3 was positively associated with KRAS status. However, there was no significant difference in the levels of the three genes across the disease stages (stages I-IV). These findings indicate that circulating exosome RNAs have a potential early detection value in pancreatic cancer, and that a distinct exosome RNA signature exists in distinguishing pancreatic cancer from healthy individuals.

Syndecan-1 and KRAS Gene Expression Signature Associates With Patient Survival in Pancreatic Cancer.

OBJECTIVES: The purpose of this study was to investigate the association of syndecan-1 (SDC1) and KRAS molecular characteristics with patient survival in pancreatic cancer. METHODS: Both SDC1 mRNA and methylation and KRAS mRNA and somatic mutations, as well as clinical data were retrieved from The Cancer Genome Alta pancreatic cancer data set for survival analyses. Kyoto Encyclopedia of Gene and Genomes pathway analysis for coexpressed genes for either SDC1 or KRAS was performed, respectively. RESULTS: A significantly negative correlation existed between SDC1 mRNA and DNA methylation. Patients with KRAS somatic mutations had a significantly higher SDC1 mRNA but lower methylation than those without the mutations. Compared with patients with KRASSDC1 signature, those with a high level of KRAS and SDC1 alone or both had a significantly elevated mortality. The adjusted hazard ratios (95% confidence interval) were 2.30 (1.16-4.54, P = 0.017) for KRASSDC1, 2.85 (1.48-5.49, P = 0.002) for KRASSDC1, and 2.48 (1.31-4.70, P = 0.005) for KRASSDC1, respectively. Several Kyoto Encyclopedia of Gene and Genomes pathways were shared, whereas there were distinct pathways between KRAS and SDC1 coexpressed genes. CONCLUSIONS: SDC1 interplays with KRAS, and targeting both KRAS and SDC1 in combination may be more beneficial to pancreatic cancer patients.