Colorectal cancer concurrent gene signature based on coherent patterns between genomic and transcriptional alterations.

BACKGROUND: The aim of the study was to enhance colorectal cancer prognostication by integrating single nucleotide polymorphism (SNP) and gene expression (GE) microarrays for genomic and transcriptional alteration detection; genes with concurrent gains and losses were used to develop a prognostic signature. METHODS: The discovery dataset comprised 32 Taiwanese colorectal cancer patients, of which 31 were assayed for GE and copy number variations (CNVs) with Illumina Human HT-12 BeadChip v4.0 and Omni 25 BeadChip v1.1. Concurrent gains and losses were declared if coherent manners were observed between GE and SNP arrays. Concurrent genes were also identified in The Cancer Genome Atlas Project (TCGA) as the secondary discovery dataset (n = 345). RESULTS: The "universal" concurrent genes, which were the combination of z-transformed correlation coefficients, contained 4022 genes. Candidate genes were evaluated within each of the 10 public domain microarray datasets, and 1655 (2000 probe sets) were prognostic in at least one study. Consensus across all datasets was used to build a risk predictive model, while distinct relapse-free/overall survival patterns between defined risk groups were observed among four out of five training datasets. The predictive accuracy of recurrence, metastasis, or death was between 61 and 86% (cross-validation area under the receiver operating characteristic (ROC) curve: 0.548-0.833) from five independent validation studies. CONCLUSION: The colorectal cancer concurrent gene signature is prognostic in terms of recurrence, metastasis, or mortality among 1746 patients. Genes with coherent patterns between genomic and transcriptional contexts are more likely to provide prognostication for colorectal cancer.

Validation of the Taiwan Chinese version of the EORTC QLQ-CR29 to assess quality of life in colorectal cancer patients.

BACKGROUND: The increasing incidence of colorectal cancer in Taiwan has generated a need for a disease-specific quality-of-life measuring instrument. We aimed to validate the Taiwan Chinese version of the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-CR29. METHODS: A total of 108 patients were interviewed. Convergent and discriminant validity, Cronbach's alpha coefficient, test-retest reliability, and known-groups comparisons were used to examine the reliability and validity. RESULTS: We found good internal consistency reliability for multi-item scales of the QLQ-C30 and QLQ-CR29, except for the cognitive function and pain scale of the QLQ-C30. Patients in the active treatment group reported compromised functional scale scores (global health status/quality of life, QLQ-C30) and worse symptoms (blood and mucus in stool, QLQ-CR29) than those in the follow-up group. Similar results were found in comparisons based on Eastern Cooperative Oncology Group (ECOG) Performance Status and Bristol Stool Scale: higher physical function/sexual interest, less fatigue/urine frequency symptoms for patients with the lowest ECOG Performance Status (Grade 0), and borderline worse stool frequency scores from Types 5 and 6 patients on the Bristol Stool Scale. CONCLUSION: The study validated the Taiwan Chinese version of the EORTC QLQ-C30 and QLQ-CR29. The clinical applicability warrants further studies with greater number of participants.

Quality of life of inguinal hernia patients in Taiwan: The application of the hernia-specific quality of life assessment instrument.

BACKGROUND: With the development of prosthetic mesh and tension free techniques, the recurrence rate following inguinal hernia repair has been reduced, and hernia outcomes research should focus on post-operative quality of life and potential complications. STUDY DESIGN: A novel hernia quality of life assessment instrument, HERQL, was developed. The HERQL questionnaire comprises a 4-item summative pain score measuring pain and discomfort resulting from various strenuous activities. Symptomatic and functional domains, as well as post-operative satisfaction are evaluated as well. RESULTS: A total of 386 HERQL surveys were completed by 183 patients with inguinal hernias. Internal consistency reliability of the summative pain score was satisfactory, with a Cronbach's alpha of 0.85. Criterion validity was examined by concomitant assessment of the pain/discomfort and health impact subscales of the EQ-5D questionnaire, with substantial to moderate correlations. Pre-operative patients reported more severe hernia protrusion, more pain during mild to heavy exercise, and worse activity restriction and health impairment than the follow-up patients, indicating clinical validity. The conceptual structure of the HERQL demostrated the causal relationship between the formative symptomatic subscales and the reflective functional status indicators. Repeated measurement of the summative pain scores revealed an estimated time effect of -1.63, which was the rate of change in the summative pain score across the pre-operative, immediately post-operative, and follow-up 3-month periods suggesting the clinical responsiveness of the HERQL. CONCLUSIONS: This study will facilitate inguinal hernia outcomes research and enhance the quality of care for this common disease by providing a validated HERQL instrument with enhanced sensitivity.

Identification of genes and pathways related to lymphovascular invasion in breast cancer patients: A bioinformatics analysis of gene expression profiles.

Surgery is the most effective treatment for breast cancer patients. However, some patients developed recurrence and distant metastasis after surgery. Adjuvant therapy is considered for high-risk patients depending on several prognostic markers, and lymphovascular invasion has become one of such prognostic markers that help physicians to identify the risk for distant metastasis and recurrence. However, the mechanism of lymphovascular invasion in breast cancer remains unknown. This study aims to unveil the genes and pathways that may involve in lymphovascular invasion in breast cancer. In total, 108 breast cancer samples were collected during surgery and microarray analysis was performed. Significance analysis of the microarrays and limma package for R were used to examine differentially expressed genes between lymphovascular invasion-positive and lymphovascular invasion-negative cases. Network and pathway analyses were mapped using the Ingenuity Pathway Analysis and the Database for Annotation, Visualization and Integrated Discovery. In total, 86 differentially expressed genes, including 37 downregulated genes and 49 upregulated genes were identified in lymphovascular invasion-positive patients. Among these genes, TNFSF11, IL6ST, and EPAS1 play important roles in cytokine-receptor interaction, which is the most enriched pathway related to lymphovascular invasion. Moreover, the results also suggested that an imbalance between extracellular matrix components and tumor micro-environment could induce lymphovascular invasion. Our study evaluated the underlying mechanisms of lymphovascular invasion, which may further help to assess the risk of breast cancer progression and identify potential targets of adjuvant treatment.