Expression of trefoil factor 3 is decreased in colorectal cancer

Abstract

In colorectal cancer (CRC), high expression of trefoil factor 3 (TFF3) is associated with tumor progression and reduced patient survival; however, bioinformatics analyses of public ‘omics’ databases show low TFF3 expression in CRCs as compared to normal tissues. Thus, we examined TFF3 expression in CRCs and matching normal tissues to evaluate its role in CRC progression. TFF3 gene expression was characterized using the bioinformatics portal UALCAN ( ). Tissue microarrays (TMAs) of archival CRC specimens (n=96) were immunostained with anti-human TFF3 antibodies. Immunohistochemical (IHC) staining intensity was semi-quantitatively scored. For this cohort, the median follow-up was 5.4 years. Associations between clinical and pathological variables were determined using Chi-square or Fisher's exact tests. Univariate disease-free survival was estimated by the Kaplan-Meier method. Omics data analyses by UALCAN showed downregulation of TFF3 expression in CRC relative to normal tissue at protein (χ 2 , P<0.0001) levels. There was a similar decreasing trend of TFF3 expression in the pathologic stages of the CRCs (RNA, χ 2 , P=0.88 and protein, χ 2 P<0.0001). UALCAN data analysis showed that TFF3 exhibited 27% lower mRNA expression in tumors with mutant TP53 (P=0.007). Confirming the findings of omics analyses, IHC analysis of TMAs exhibited lower TFF3 expression in 95.6% (65 of 68) of the available normal-tumor matching pairs (χ 2 , P<0.0001). There was no statistically significant association of tumor TFF3 expression with patient sex, race/ethnicity, tumor location within the colorectum, Tumor, Node, Metastasis (TNM) stage, lymph node metastasis, or surgical margins. However, low TFF3 IHC staining in tumor tissue was associated with histological grade (P=0.026). Kaplan-Meier survival analysis showed no prognostic value of low TFF3 expression relative to those with high expression (log-rank, P=0.605). Our findings demonstrate low expression of TFF3 in CRCs. Association between low TFF3 and histopathological features suggests involvement of this molecule in progression of CRC.

Expression of MHC class I polypeptide-related sequence A (MICA) in colorectal cancer

“…As described before [9,21], IHC was performed according to manufacturer's instructions provided in Vector Labs's VECTASTAIN Elite Avidin-Biotin Complex Staining Kit (Cat# PK-6101 Vector Laboratories Inc., Burlingame, CA, USA). Following antigen retrieval with citrate buffer (pH 6.0) for 20 min, and incubation with 3% hydrogen peroxide, the FFPE TMA sections were deparaffinized and rehydrated during 10 min.…”

Proteomics profiling for the global and acetylated proteins of papillary thyroid cancers

“…Among them, KRT1B protein, dermcidin and keratin, type II cytoskeletal 5 are not well addressed in thyroid cancer. Except UPF0764 protein and A-gamma globin Osilo variant, 8 of the top 10 down-regulated DEPs have also mentioned in other types of cancers, adhesion G-protein-coupled receptor G1 (decreased) [ 28 ], keratin-type I cytoskeletal 16 [ 27 ], Huntingtin interacting protein-1 (decreased) [ 29 ], ribosomal protein L19 (increased) [ 30 ], Beta-1,4-galactosyltransferase 1 (negatively regulates cell survival) [ 31 ], trefoil factor 3 (decreased) [ 32 , 33 ], hemoglobin alpha-2 globin mutant [ 34 ], sulfotransferase [ 35 , 36 ]. Contrarily, only 2 proteins, trefoil factor 3 and sulfotransferase are addressed in thyroid cancer.…”

Diagnostic utility of trefoil factor families for the early detection of lung cancer and their correlation with tissue expression

“…Moreover, TFF3 was also reported to inhibit the growth of colorectal cancer cells, in a cell-type dependent manner (32). In clinical specimens, TFF3 expression was reported to be lower in colorectal cancer compared with normal tissue (33). These observations indicate that TFF1 and TFF3 can also function as tumor suppressor-like proteins.…”