Abstract
Background: While protein O-fucosyltransferase 1 (POFUT1) overexpression has been recently proposed as a potential biomarker for different cancer types, no study was carried out on POFUT1 implication in colorectal cancer (CRC). Methods: Data from 626 tumors and 51 non-tumor adjacent tissues available in FireBrowse had been used in this study. Statistical analyses on POFUT1 expression and gene copy number, NOTCH receptors (main targets of POFUT1 enzymatic activity) expression and association of POFUT1 and NOTCH1 expressions with clinical parameters were investigated. Data were completed by POFUT1 histological labeling on six tumor tissues from patients with CRC. Results: We found that POFUT1 is overexpressed from the stage I (p < 0.001) and 76.02% of tumors have a 20q11.21 amplification, associated in 90.13% of cases with a POFUT1 overexpression, compared to non-tumor adjacent tissues. The POFUT1 copy number in tumors is mainly between 2 and 3. POFUT1 is positively correlated with NOTCH1 (rs = 0.34, p < 0.001), NOTCH3 (rs = 0.087, p = 0.0297), and NOTCH4 (rs = 0.097, p = 0.0148) expressions, while negatively correlated with NOTCH2 expression (rs = −0.098, p = 0.0142). POFUT1 overexpression is markedly associated with rectal location, non-mucinous adenocarcinoma and cancer stages IV and M1. NOTCH1 overexpression is only associated with rectal location and non-mucinous adenocarcinoma. Conclusion: We conclude that POFUT1 is overexpressed in CRC from stage I, and its high expression is associated with metastatic process, probably through NOTCH pathway activation. Then, POFUT1 could represent a potential novel biomarker for CRC diagnosis.
Highlights
Colorectal cancer (CRC) is the third most commonly diagnosed cancer in males and the second in females with 1.65 million new cases and almost 835,000 deaths in 2015 [1]
We conclude that protein O-fucosyltransferase 1 (POFUT1) is overexpressed in colorectal cancer (CRC) from stage I, and its high expression is associated with metastatic process, probably through NOTCH pathway activation
Bioinformatics combined with immunohistochemistry, western blot and gene copy number analysis had been used as an approach to determine if POFUT1 could be a potential novel CRC biomarker
Summary
Colorectal cancer (CRC) is the third most commonly diagnosed cancer in males and the second in females with 1.65 million new cases and almost 835,000 deaths in 2015 [1]. POFUT1 overexpression was detected in oral squamous cell carcinoma and correlated with an increase of tumor size [31] In hepatocellular carcinomas, it was associated with a poor prognosis, as it induces an aberrant activation of NOTCH pathway, which promotes cell proliferation, migration and invasion [32]. POFUT1 gene is localized in the 20q11.21 region, which is frequently amplified in tumor cells as for breast [34] and gastric cancers [35], acute myeloid leukemia [36] and colorectal cancer with poor prognosis [37] In this last case, a positive correlation is reported between. In parallel, based on six different colorectal tumors, we detected POFUT1 and estimated the number of POFUT1 copies
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