Clinical significance and prognostic value of Forkhead box A1 expression in human epithelial ovarian cancer

Abstract

Abstract. Forkhead box (FOX) A1 is a member of the FOX family of transcription factors, which serve a function in numerous types of tumor. The present study assessed the potential role of FOXA1 in human epithelial ovarian carcinoma (EOC). Total RNA was isolated from 16 fresh-frozen EOC tumors with paired corresponding non-malignant ovarian epithelium tissues, and FOXA1 expression was analyzed using reverse transcription-quantitative polymerase chain reaction. Immunohistochemical analysis was performed to evaluate FOXA1 expression in 110 epithelial ovarian carcinoma tissue specimens (including 80 serous papillary adenocarcinoma, 9 clear cell carcinoma, 12 endometrioid adenocarcinoma, 5 mucinous carcinoma and 4 transitional cell carcinoma specimens), 24 benign ovarian tumor surface epithelium tissues and 10 normal ovarian tissue samples. The present study analyzed the association between FOXA1 expression and clinical characteristics in patients with EOC. The Kaplan-Meier method was used for survival analysis. The results of the present study revealed that FOXA1 mRNA expression was significantly increased in EOC tissues compared with paired normal ovarian samples (P=0.014). The immunohistochemical expression of FOXA1 in EOC tissues was associated with the FIGO grade, differentiation status and overall survival time (all P<0.05). Finally, the significance of FOXA1 expression in the prognosis of the patients was evaluated. The results of Kaplan-Meier survival curve revealed that high FOXA1 expression was associated with decreased overall survival time in the patients, relative to low FOXA1 expression (P=0.0132). In conclusion, FOXA1 is overexpressed in EOC and associated with clinicopathological features, including overall survival time. FOXA1 potentially represents a novel biomarker and therapeutic target for EOC.

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 .…”

“…In recent years, the relationship between the expression of FOXA1 and prognosis has been investigated in various cancers, including breast and prostate cancer. [18][19][20][21][22][23][24][25][26][27][29][30][31][32][34][35][36][37] However, the influence of FOXA1 expression on prognosis differs according to the primary site. In SDC, we demonstrated that a high FOXA1 expression level was a good prognostic marker.…”

“…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.…”