Low prostaglandin-endoperoxide synthase-2 gene expression in colorectal carcinomas may predict poorer survival.

Abstract

Introduction: Prostaglandin-endoperoxide synthase-2 (ptgs2), otherwise called Cyclooxygenase 2, is overexpressed in colorectal carcinoma (CRC) compared to normal tissues. However, the impact of differential expression among ptgs2-positive tumours on CRC prognosis has not been well investigated. By sub-stratifying positive tumour expression, this study determined its potential influence on patients' outcomes.

Methods: The Cancer Genome Atlas database was explored to determine CRC cases with RNA-Sequence (RNA-Seq) transcript data and matched clinicopathological data alongside gene copy number variation and methylation status. Descriptive, chi-square, Fisher exact, Linear-by-Linear associations, logistic and Kaplan-Meier statistics were used to determine proportions, associations, predictors and survival between ptgs2 and tumour parameters using Statistical Package for Social Sciences version 20. Two-tailed p-value <0.05 was accepted as statistically significant.

Results: There were 534 CRC classified predominantly as adenocarcinoma not otherwise specified (86.3%) and mucinous carcinoma (12.4) histologically included in this study. Marker (ptgs2) expression ranged from 0.02 FPKM-131.89 FPKM, (Median 1.4 FPKM). The majority of the cases (53.4%) were diagnosed at an early stage and showed high ptgs2 RNA-Sequence (RNA-seq) expression in 51.5% (275/534). Significant associations were seen between ptgs2 expression and histological subtype (p < 0.001), lymphovascular invasion (p = 0.013), pN2 stage (> 6 positive lymph nodes) (p = 0.011) and American Joint Committee on Cancer Staging stage (p = 0.028), and these all had lower ptgs2 expression. On regression analysis, histological differentiation emerged as a predictor of ptgs2 expression (Odds ratio 2.749, 95% confidence interval 1.479-5.108, p < 0.001). Also, gene methylation was associated with reduced ptgs2 expression. Overall survival was significantly inferior among individuals with low ptgs2 tumours (p = 0.018) while that for disease-free survival was non-significant (p = 0.327).

Conclusion: CRCs with low ptgs2 transcripts are associated with poorer survival. This finding suggests a need for closer follow up and tailored adjuvant therapy for these patients.