| BackgroundThe outcome of the treatment for gastric cancer patients is not satisfactory, despite of some improvements having been achieved in recent years.PurposeWe aimed to explore the expression of LIF and LIFR in gastric cancer and their biological effects on proliferation, invasion, tumor growth and prognosis.Methods1. ELIS A for LIF serum level was performed in 208 cases of gastric cancer,67 cases of gastritis patients, and 70 cases of healthy persons. The expressions of LIF and LIFR were tested in 128 cases of paraffin cancer specimens and 40 cases of fresh tumor tissue and matched adjacent normal mucosa tissue. The correlations between LIF, LIFR and clinicopathological characteristics were analyzed.2. Among different gastric cancer cell lines, the one with the highest expression of LIFR and lowest expression of LIF was to be found. The biological effects of LIF addition and silencing LIFR on the proliferation, cell cycle, cell apoptosis, invasion, migration and tumor growth of MGC803 gastric cancer cell line were detected by CCK-8, EdU, plate clone, flow cytometry, transwell and nude mouse transplantation tumor experiment.3. The relationship between LIF and Hippo-YAP signaling was examined by Western blot. The effect of LIF on the proliferation of YAP-siRNA MGC803 cell line was detected by CCK-8 test.Results1. The LIF serum level of gastric cancer patients, gastritis patients, and healthy persons were 8.650±6.282 pg/ml,4.325±1.824 pg/ml, and 3.344±1.918 pg/ml, respectively. The level of gastric cancer patients was significantly higher than those of gastritis patients (P=0.003) and healthy persons (P<0.001). The diagnostic cut-off value, sensitivity, specificity and accuracy of LIF for gastric cancer patients were 5.585 pg/ml,88.14%, 81.82%, and 85.64%, respectively. According to IHC analysis, LIF and LIFR positive rates were significantly higher in gastric cancer than in normal mucosa (P<0.001). LIF and LIFR expressions were found to be associated with tumor differentiation (P=0.021), vascular invasion (P=0.001), T stage (P=0.001), lymph node metastasis (P=0.001) and pTNM stage (P=0.012). There was a strong correlation between LIF and LIFR protein and mRNA expression by Pearson’s test (r=0.598, P<0.001 and r=0.628, P<0.001, respectively). LIF and LIFR were found to be independent factors associated with patient’survival by Cox regression analysis (P=0.009 and P=0.034, respectively).2. MGC803 cancer cell line had the highest expression level of LIFR and the lowest expression level of LIF. Addition of LIF could promote proliferation, invasion, migration, anti-apoptosis and tumor growth in MGC803 cancer cell line (P<0.001). Silencing LIFR expression could inhabit those malignant biological behavior of MGC803 cancer cell line compared with negative control. And the addition of LIF in the LIFR-shRNA cell could not promote tumorgenesis.3. LIF could decrease the phosphorylated level of core elements in the Hippo-YAP signaling (P<0.001) and promote nuclear translocation of YAP protein. Additionally, LIF could not promote the proliferation of the YAP-siRNA cell.Conclusions1. LIF promoted the gastric cancer tumorgenesis, and could be employed in the diagnosis for gastric cancer patients. It also could be employed as a potential indicator for predicting proliferation, growth, invasion, immigration and metastasis in gastric cancer cells and prognosis of patients with gastric cancer.2. LIF could promote the proliferation, invasion, metastasis and other malignant biological behavior of MGC803 cancer cell line. While silencing LIFR expression could inhibited tumorgenesis. The addition of LIF in LIFR-shRNA cell could not promote malignant biological behavior of cancer. These results showed that LIF had an effect on cell through combination of LIFR.3. LIF could effectively inhibit the phosphorylated level of MST1/2, LATS and YAP protein. These results showed that the effect of LIF on cell was through Hippo-YAP signaling, resulting nuclear translocation of YAP protein.4. LIF may play an important role in proliferation, invasion and metastasis of gastric cancer, and thus may be a useful target fot treatment. Inhibition of LIFR with shRNA technique could be a new option for the treatment in gastric cancer. |
PDF Full Text Request