Abstract:Objective To study the expression of eukaryotic translation initiation factor 3 subunit H(EIF3H) and pre-mRNA processing factor 19(PRP19) in esophageal squamous cell carcinoma(ESCC), and to analyze their correlation with Hippo/YAP pathway and prognostic value. Methods The cancer tissues and adjacent tissues of 120 ESCC patients admitted to the Department of Hematology and Oncology, Qinghai Provincial Traditional Chinese Medicine Hospital from February 2017 to February 2021 were selected. qPCR was used to detect the mRNA expression of EIF3 H, PRP19, Hippo/YAP pathway-related genes[mammalian sterile 20-like kinase 1(MST1), Yes associated protein 1(YAP1)], and immunohistochemistry was used to detect the protein expression of EIF3 H and PRP19.Pearson correlation coefficient was used to analyze the correlation between EIF3 H, PRP19 mRNA expression and Hippo/YAP pathway-related gene mRNA expression; Kaplan-Meier curve and Cox regression were used to analyze the prognostic factors of ESCC patients.Results The relative expression levels of EIF3 H, PRP19, MST1 and YAP1 mRNA in ESCC cancer tissues were higher than those in adjacent tissues( t/P=32.933/<0.001,39.204/<0.001,32.492/<0.001,41.524/<0.001); Pearson correlation analysis showed that the expression of EIF3H and PRP19 mRNA was positively correlated with the expression of MST1 and YAP1 mRNA in ESCC patients(EIF3H: r/P=0.663/<0.001,0.706/<0.001; PRP19: r/P=0.678/<0.001,0.724/<0.001); the positive rates of EIF3 H and PRP19 protein in cancer tissues were 65.00 %(78/120) and 63.33 %(76/120), respectively, which were higher than 5.00 %(6/120) and 6.67%(8/120) in adjacent tissues, the difference was statistically significant( χ2/P=94.945/<0.001,84.689/<0.001);The positive rates of EIF3H and PRP19 protein in ESCC patients with TNM stage Ⅲ and lymph node metastasis were higher than those in TNM stage Ⅰ~ Ⅱ and no lymph node metastasis( χ2/P=17.802/<0.001,12.624/<0.001,16.800/<0.001,12.146/<0.001); The 3-year overall survival(OS) of 120 ESCC patients was 58.33 %(70/120), the 3-year OS of EIF3H positive group and PRP19 positive group was 43.59 %(34/78) and 40.79 %(31/76), respectively, which was lower than 85.71 %(36/42) and 88.64 %(39/44) of EIF3H negative group and PRP19 negative group, and the difference was statistically significant(Log Rank χ2=20.970,19.350,P<0.001). TNM stage Ⅲ, lymph node metastasis, EIF3 H positive and PRP19 positive were independent risk factors affecting the prognosis of ESCC patients[HR(95%CI)=1.665(1.145-2.421),1.501(1.205-1.869),1.539(1.209-1.958),1.391(1.139-1.699)].Conclusion The elevated expression of EIF3H and PRP19 in ESCC may promote tumor progression through the Hippo/YAP pathway and serve as markers for assessing the prognosis of ESCC.
Key words:Esophageal squamous cell carcinoma ; Eukaryotic translation initiation factor 3 subunit H ; Pre-mRNA processing factor 19 ; Hippo/YAP pathway ; Prognosis
Funding: Health Research Project of Qinghai Province(2021-wjzdx-77)