The clinical significance of forkhead box protein A1 and its role in colorectal cancer

Abstract

Forkhead box protein A1 (FOXA1) is a transcription factor; recent studies have reported that FOXA1 has an oncogenic or tumor suppressive role in human malignancies, and its expression is associated with the prognosis of patients with cancer. However, further studies are required to determine the clinical significance of FOXA1 and its role in colorectal cancer (CRC). In the present study, FOXA1 expression was detected in 90 samples of CRC tissues and matched noncancerous tissues using immunohistochemistry. In these cases, FOXA1 expression was detected in 57.8% (52/90) of the CRC samples, whereas only 37.8% (34/90) of the noncancerous specimens exhibited a positive FOXA1 signal. In addition, the present study demonstrated that the mRNA expression levels of FOXA1 were significantly increased in CRC tissues compared with in matched tumor-adjacent tissues. Furthermore, the positive expression of FOXA1 was associated with poor clinicopathological characteristics of CRC, including poor tumor differentiation, large tumor size, lymph node metastases and advanced tumor-node-metastasis tumor stage. Notably, patients with CRC with positive FOXA1 expression exhibited a significantly reduced 5-year survival rate compared with those with negative FOXA1 expression. Multivariate Cox regression analysis revealed that FOXA1 expression was an independent prognostic indicator for patients with CRC. In addition, FOXA1 knockdown evidently inhibited cell proliferation and induced apoptosis in SW480 and HCT116 CRC cells. Notably, FOXA1 knockdown also prominently reduced the expression of yes-associated protein (YAP) in SW480 and HCT116 cells. In conclusion, the results of the present study indicated that FOXA1 may be considered a potential prognostic marker, and may promote tumor growth of CRC by upregulating YAP expression.

The high expression of FOXA1 is correlated with a favourable prognosis in salivary duct carcinomas: a study of 142 cases

“…In recent years, the relationship between the expression of FOXA1 and prognosis has been investigated in various cancers, including breast and prostate cancer . However, the influence of FOXA1 expression on prognosis differs according to the primary site.…”

“…A favourable subtype of breast cancer, luminal A type, responds well to anti‐hormonal therapy and expresses FOXA1 highly, which may act as an oestrogen regulatory gene . Conversely, an opposite correlation has been observed in prostatic, colorectal, liver, lung, ovarian and gastric cancers . In the prostate, FOXA1 plays an important role in early morphogenesis and cell differentiation .…”

“…FOXA1 knockdown by siRNA causes the suppression of cell proliferation in prostate cancer cell lines . Similarly, in some hormone‐independent cancers, such as cancers of colorectal, lung and liver origins, FOXA1 promoted proliferation, invasion and migration . More work is needed to elucidate the organ‐ or tumour‐specific functional roles of FOXA1 in the development and progression of the disease.…”

“…Androgen receptor requires its co‐regulatory protein forkhead box protein A1 (FOXA1) to form a productive transcription complex on chromatin to mediate the cell‐ and tissue‐specific regulation of the target gene expression, and to bring about the diverse biological actions of androgens . FOXA1 is known frequently as a ‘pioneer factor’, which binds highly compacted chromatin and renders bound genomic regions more accessible to other transcription factors, and which is expressed in many organs, including the prostate and mammary gland …”

“…13 FOXA1 is known frequently as a 'pioneer factor', which binds highly compacted chromatin and renders bound genomic regions more accessible to other transcription factors, [14][15][16][17] and which is expressed in many organs, including the prostate and mammary gland. [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] Only one previous report on a small study population has analysed the FOXA1 expression, as well as FOXA1 gene mutations in SDCs. 28 However, the clinicopathological significance remains unknown.…”