| 【Background】Gastric cancer is a disease with one of the poorest prognoses, being the second cause oftumor-related mortality in the world. Its five-year overall survival is25%orless,especially in USA, Europe, and China. Every year,1million new cases of gastriccancer are diagnosed and700,000die of this disease worldwide. Most patients with gastriccancer are diagnosed with advanced gastric cancer, and overall survival rate remains poor.To provide new insights into the pathology of the disease and to permit earlier diagnosis,there is a need for new prognostic tumor markers that are more sensitive than thosecurrently available, such as CEA and CA19-9.Nevertheless, the diagnosis of gastriccancer and the cure rate is still low, the prognosis is poor. Thus, the discovery of newtumor markers for the early diagnosis is very important. Previous reports have showed thatLRPPRC was highly expressed in most cancers, such as hepatoma cancer, lungadenocarcinoma, esophageal squamous cell carcinoma, colon cancer and lymphoma, andProstate Cancer. However, the LRPPRC expression in gastric cancer and its correlationwith gastric cancer is still unclear. In the study, we will research the relationship of inLRPPRC expression and gastric cancer. 【Aims】1. First, we want to explore the correlation between LRPPRC protein expression levelsand clinicopathological parameters of gastric cancer.2. Second, we want to observe the function and role of LRPPRC in gastric cancerdevelopment and progression.【Methods】1.Immunohistochemistry was used to detect the LRPPRC expression level in253cases ofgastric carcinoma and adjacent tissues. And the correlation between LRPPRC proteinexpression levels and clinicopathological parameters of gastric cancer was analysised bySPSS.2.Western Blot was used to detect the protein expression level of LRPPRC in SV40transfection immortalized gastric mucosa epithelial cells GES-1and six gastric cancer celllines (KATOIII, SGC7901, BGC823, MKN45, MKN28, and XGC9811).3. LRPPRC specific siRNA was constructed and its inhibitory effect in gastric cancercells was validated by Western Blot.4. MTT assay was used to observe the proliferation ratio in LRPPRC inhibited gastriccancer cells.5. Transwell assay was used to observe the metastasis and invasion phenotype in LRPPRCinhibited gastric cancer cells.【Results】1.Immunohistochemistry found that positive LRPPRC expression in gastric cancer tissues(219/253,86.6%) was significantly higher than that in paired noncancerous tissues(132/253,52.2%)(P＜0.001).further statistical analysis of the relationship betweenLRPPRC expression and clinical cases parameters with gastric cancer patients,Resultshowed that high expression of LRPPRC was significantly correlated with the depth oftumor infiltration (T stage P＜0.001, N stage P＜0.001and M stage P=0.002),whereas notwith age, gender, tumor locus, tumor grade and TNM stage. To further study the prognostic value for the diagnosis of expression levels LRPPRC in gastric cancer, weconducted a survival analysis. The overall survival analysis using the Kaplan-Meyermethod revealed that the prognosis of gastric cancer patients whose tumors with higher ormoderate LRPPRC expression showed significantly shorter survival than those with no orweak LRPPRC expression (P＜0.001). Univariate analysis showed that the followingfactors were significantly related to postoperative survival: depth (P=0.004), lymph nodemetastasis (P=0.007), distant metastasis (P＜0.001),TNM stage (P=0.004), and LRPPRCexpression (P＜0.001). Furthermore, a Multivariate analysis indicated that TNM stage(P=0.004), and LRPPRC expression (P<0.001) were independent prognostic factors ofoverall survival for the patients with gastric cancer2. Western Blot results showed that LRPPRC expression level in gastric cancer cells washigher than that in immortalized gastric mucosal cells GES-1. In addition, LRPPRCexpression level in gastric cancer SGC7901, BGC823, MKN45and XGC9811cells washigher than that in KATOIII and MKN28cells. And LRPPRC specific siRNA couldsignificantly inhibit LRPPRC expression level in SGC7901, BGC823, MKN45andXGC9811cells.4. MTT results showed that knock down LRPPRC expression significantly inhibitedSGC7901cells proliferation in vitro, but do not affect the growth rate of BGC823,MKN45and XGC9811cells.5. Transwell experiments showed that inhibited LRPPRC expression could significantlyreduced XGC9811invasion and migration.【Conclusions】Our results showed that LRPPRC expression in gastric cancer tissues is significantlyhigher than that in paired control tissue(p＜0.001). Patients with higher LRPPRCexpression showed a poorer overall survival rate than those with lower LRPPRCexpression(p＜0.001). Multivariate analysis demonstrated that lymph nodemetastasis(N), distant metastasis(M), TNM stage, and LRPPRC expression was anindependent prognostic factor for gastric cancer (P=0.004,P=0.002, P=0.017, P=0.004 respectively).Moreover, Western Blot showed that LRPPRC expression was increased inSGC7901, BGC823, MKN45and XGC9811cells. The in vitro proliferation and transwellassay showed that LRPPRC expression is inversely associated with gastric cancer cellsgrowth, invasion and migration.In conclusion, our results suggested that LRPPRC could be used as a predictivemarker for patient prognosis of gastric cancer and may be a novel therapeutic target forgastric cancer in future. |
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