Evaluation of Glycosylated PTGS2 in Colorectal Cancer for NSAIDS-Based Adjuvant Therapy

Abstract

Observational/retrospective studies indicate that prostaglandin-endoperoxide synthase-2 (PTGS2) inhibitors could positively affect colorectal cancer (CRC) patients’ survival after diagnosis. To obtain an acceptable cost/benefit balance, the inclusion of PTGS2 inhibitors in the adjuvant setting needs a selective criterion. We quantified the 72 kDa, CRC-associated, glycosylated form of PTGS2 in 100 frozen CRC specimens and evaluated PTGS2 localization by IHC in the same tumors, scoring tumor epithelial-derived and stroma-derived fractions. We also investigated the involvement of interleukin-1 beta (IL1β) in PTGS2 induction, both in vitro and in CRC lysates. Finally, we used overall survival (OS) as a criterion for patient selection. Glycosylated PTGS2 can be quantified with high sensibility in tissue lysates, but the expression in both tumor and stromal cells limits its use for predictive purposes. Immunohistochemistry (IHC) analysis indicates that stromal PTGS2 expression could exert a protective role on patient OS. Stromal PTGS2 was prevalently expressed by cancer-associated fibroblasts exerting a barrier function near the gut lumen, and it apparently favored the antitumor M1 macrophage population. IL1β was directly linked to gPTGS2 expression both in vitro and in tumors, but its activity was apparently prevalent on the stromal cell population. We suggest that stromal PTGS2 could exert a positive effect on patients OS when expressed in the luminal area of the tumor.

Bioinformatics Analysis of Differentially Expressed Genes and Protein–Protein Interaction Networks Associated with Functional Pathways in Ulcerative Colitis

“…Song et al [ 31 ] showed that reducing PTGS2 expression can help to reduce the occurrence of colorectal cancer. This possibility is consistent with the results presented by Venè et al [ 32 ], which showed that PTGS2 inhibitors have a positive effect on the prognostic survival of patients with colorectal cancer. Other researchers have shown that PTGS2 expression in colon tissue increases prostaglandin synthesis, which can cause visceral hypersensitivity in patients with irritable bowel syndrome [ 33 ].…”

Identification S100A9 as a potential biomarker in neuroblastoma

“…The expression levels of TAC1, PTGS2 and FGF1 in resected specimen of NB patients with or without metastasis were then validated by qRT-PCR. Although the expression of TAC1, PTGS2 and FGF1 were related with many kinds of tumorigenesis, such as non-small cell lung cancer, pancreatic ductal cancer, colorectal cancer, squamous cell carcinoma, gastric cancer and clear cell renal cell carcinoma [26][27][28][29][30][31][32][33], but these genes expression did not exhibit significant change as expected as the microarray results, indicating that these three genes may not the pivotal gene that participate in the metastasis of NB.…”

Random Forest approach for the identification of relationships between epigenetic marks and its application to robust assignment of chromatin states

“…For example, among these genes we found PTGS2. This gene has been associated with inflammatory stimuli and expressed in tumor cells of colorectal cancer [49, 50]. Another example is VEGF-A, a gene that encodes an angiogenic factor that has been detected up-regulated in different types of tumors such as colorectal cancer [51, 52].…”