Significant Association Of YAP1 And HSPC111 Proteins With Poor Prognosis In Chinese Gastric Cancer Patients

Objective:In the present study,we evaluate the expression pattern and relationships between YAP1 and HSPC111(HBV pre-S2 trans-regulated protein 3)in gastric cancer(GC),and assess the clinical significance of them.Methods:The Cancer Genome Atlas database was used to evaluate mRNA expression of HSPC111 as well as core components of Hipoo-YAP1 pathway and poor prognosis of GC patients in GC tissues.At the same time,Western blot(WB)and qRT-PCR were applied to assess protein and RNA levels of YAP1 and HSPC111 in 30 paired gastric cancer(GC)samples.Formalin-fixed,paraffin-embedded samples from 120 GC patients were collected for immunohistochemistry analysis for staining pattern of YAP1 and HSPC111 in gastric cancer(GC)tissues at the Department of Pathology of the First Affiliated Hospital of Nanchang University,from January 2009 to December 2012.Next,we use WB and qRT-PCR to detect the correlation between YAP1 and HSPC111 in GC cell lines and gastric cancer.In addition,the chi-square test was adopted to examine the relationships of YAP1 and HSPC111 expression with reference to clinical characteristics.Finally,Kaplan-Meier analysis and log-rank testing were used to evaluate the prognostic value of YAP1 and HSPC111 expression in GC(gastric cancer).Results:1)Results of TCGA(the Cancer Genome Atlas database)revealed that high YAP1 mRNA expression was significantly linked to poor prognosis of GC patients,and that mRNA levels of HSPC111 evidently increased in GC tissues.2)In GC cell lines and clinical samples,increased expressions of both YAP1 and HSPC111 were also detected.3)A correlation between expression levels of HSPC111 and nuclear and cytoplasmic YAP1 in clinical samples(nuclear:r = 0.2615,P = 0.004;cytoplasm:r =-0.3721,P<0.001)and cell lines was also discovered by Spearman correlation coefficient analysis and WB(western blot),respectively.4)The chi-square test determined that nuclear expression of YAP1 was positively correlated with clinical stage(P = 0.041),tumor size(P = 0.023),and lymph node metastasis(P = 0.007),HSPC111 expression,by contrast,was concerned with lymph node metastasis(P = 0.014).5)Kaplan-Meier analysis and log-rank testing indicated that patients who were HSPC111-and nuclear YAP1-positive were related to the worst prognosis(34.5 ± 4.8 months,p = 0.001).And univariate and multivate Cox regression revealed that depth of invasion(P = 0.014),tumor size(P= 0.010)and nuclear YAP1 expression(P = 0.000)might act as independent prognostic factors for GC patients.Conclusion:Our analysis revealed that expression levels of YAP1 and HSPC111 are both up-regulated in gastric cancer.In addition,our data show that elevated expression of YAP1 and HSPC111 is negatively associated with the GC patient prognoses.Statistical analysis demonstrated that an increase in the expression of these two proteins was associated with the poorest survival rate among GC patients.We suggested strong correlation between YAP1 and HSPC111 and firstly detected that the Hippo-YAP1 pathway might play a crucial role in ribosomal biogenesis.