VGLL4 with low YAP expression is associated with favorable prognosis in colorectal cancer

Abstract

The Hippo pathway is a tumor suppressive pathway regulating Yes-associated protein-TEA domain-containing sequence-specific transcription factor (YAP-TEAD) complex. VGLL (Vestigial-like) proteins are transcriptional cofactors competing with YAP for TEAD binding and interfering oncogenic activity of YAP-TEAD complex. We evaluated the expression of VGLL4, YAP, and TEAD4 and assessed their correlations with clinicopathologic factors and prognostic effects in 295 colorectal cancers. VGLL4 was positive in 164 (55.6%) cases and correlated with small tumor size, low pT classification, and absence of lymph node metastasis. YAP and TEAD4 were highly expressed in 138 (46.8%) cases and 144 (48.8%) cases, respectively, and high expressions were associated with presence of lymphovascular invasion and lymph node metastasis, or distant metastasis. VGLL4 expression was significantly correlated with low YAP expression (p < 0.001) and had significantly better overall survival than negative expression (p < 0.001). High YAP (HR, 2.108; 95% confidence interval, 1.239-3.584; p = 0.006) and TEAD4 (1.724; 1.021-2.912; p = 0.042) expressions were associated with poor overall survivals. The combined VGLL4 pos YAP low expression showed the best overall survival than other groups (p < 0.001). VGLL4 expression (0.381; 0.212-0.683; p = 0.001) and combined VGLL4 pos YAP low expression (0.227; 0.108-0.475; p < 0.001) were independent good prognostic factors in colorectal cancers. The expressions of VGLL4, YAP, and TEAD4 can be used as prognostic markers in colorectal cancer patients.

High YAP and TEAD4 immunolabelings are associated with poor prognosis in patients with gallbladder cancer

“…Immunohistochemical staining was carried out as previously described [17]. Briefly, 4‐μm thick sections were cut from each TMA and deparaffinized and hydrated in xylene and serially diluted ethanol.…”

“…The immunohistochemical staining for YAP and TEAD4 was evaluated as previously described [12, 17]. The nuclear YAP and TEAD4 immunolabelings of the tumor cells were scored by multiplying the staining intensity (0, none; 1+, weak; 2+, moderate; and 3+, strong) and the proportion of stained cells (0, none; 1, <25%; 2, 25–50%; 3, 50–75%; and 4, >75%), thus having a range from 0 to 12.…”

“…YAP is a transcriptional cofactor that controls oncogenic functions such as growth factor‐independent cellular proliferation, epithelial‐mesenchymal transition, cellular invasion, and metastasis [10, 11]. Nuclear YAP immunolabeling is associated with aggressive clinicopathologic behavior with poor prognosis in several types of cancers including gastric, cervix, ovary, and breast cancers [12–17]. Recently, Garcia et al.…”

“…TEAD4 regulates the transcriptional activity of several oncogenes that result in tumor progression, invasion, and distant metastasis [13, 19, 20]. Increased TEAD4 expression has been identified in several cancers including colorectal, breast, and stomach cancer, and correlated with unfavorable cancer behaviors [12, 17, 21, 22]. However, no previous studies to date have systematically evaluated the immunolabeling levels of YAP and TEAD4 and their correlation with clinicopathologic characteristics in gallbladder cancers.…”

VGLL4 Promotes EV71 Virus Proliferation and Accelerates the Apoptosis of Infected RD Cells

“…Vestigial-like Family Member 4 (VGLL4) is an important transcription cofactor. Relevant studies have shown that it can be a tumor suppressor to in uence the occurrence and development of tumors by promoting apoptosis of tumor cells [4,14,20]. In normal cells, it can also promote apoptosis as an inhibitor of apoptosis protein (IAP)-interacting protein [3,16].…”