The Expression Of OCT4、PTTG1、TANGL2and The Effect Of TGF-β Signaling Pathways On TANGL2Metastasis In Pancreatic Cancer

Objective1. To investigate the role and molecular mechanisms of OCT4in pancreatic cancer, analysis the relationship between OCT4and clinicopathology in pancreatic cancer.2. To investigate the expression and clinical significance of PTTG1in human primary pancreatic cancer.3. To investigate the role of TGF-β1and TAGLN2in pancreatic cancer, analysis the relationship of TGF-β1and TAGLN2in pancreatic cancer.Investigate the expression of TGF-β1and TAGLN2in the Han nationality and Uyghur nationality with pancreatic cancer.Method1. The clinical significance of OCT4expression was assessed by immunohisto-chemical assay using a tissue microarray procedure in cancer tissues, and its expression was detected in pancreatic cancer cells with different degrees of differentiation. A loss-of-function approach was used to explore the effects of lentiviral vector-mediated OCT4shRNA (Lv-shOCT4) on the biological behaviors such as proliferative activities and invasive potential of tumor cells, indicated by MTT and Transwell assays, respectively.2. Seventy-five cases of human pancreatic cancer tissues were collected. The expression of PTTG1protein was assessed using immunohistochemistry (IHC) through tissue microarray procedure. The clinicopathologic characteristics of all patients were recorded. 3. one hundred and six cases of human pancreatic cancer tissues were collected. The expression of TAGLN2, TGFβRⅡ、p-Smad2/3protein was assessed using Immunoisto-chemistry (IHC) through tissue microarray procedure. The clinicopathologic characteristics of all patients were recorded. The expression of TAGLN2、TGFβⅡ、 p-Smad2/3protein was assessed using Western blot method in forty-six cases of human pancreatic cancer tissues.Results1. The expression of OCT4protein in cancer tissues was significantly elevated compared to that in adjacent non-cancerous tissues (ANCT)(65.0%vs.42.5%, P=0.005), and correlated with tumor differentiation (P=0.008); Knockdown of OCT4inhibited proliferation and invasion of pancreatic cancer cells (Panc-1) expressing high level of OCT4, accompanied with decreased expression of AKT.2. The expression of PTTG1in cancerous tissues showed the positive staining mainly in the cytoplasm, and was found in cancerous tissues with higher strong reactivity rate compared with the adjacent non-cancer tissues (ANCT)(56.0%vs.22.7%, P=0.000), elevating with the ascending order of tumor malignancy.3. The positive expression of PTTG1was found associated with the gender of pancreatic cancer patients, but did not correlate with their age, athological styles, tumor size, tumor sites, TNM staging, perineural infiltration and distant metastasis (eachP>0.05).4. The straining of TAGLN2. TGFβRⅡ, p-Smad2/3mainly located in cell plasma, The expression of TAGLN2、TGFβRⅡ、p-Smad2/3protein in cancer tissues was significantly elevated compared to that in ANCT (P<0.05);5. The positive expression of TAGLN2. TGFβRⅡ、p-Smad2/3was found associated with athological styles, TNM staging and perineural infiltration (each P<0.05). And TGFβRⅡ, p-Smad2/3was found associated with distant metastasis (each P<0.05).6. The positive expression of TAGLN2has positive correlation with TGFβRⅡ、 p-Smad2/3in pancreatic cancer tissues.7. The positive expression of TAGLN2, TGFβRⅡ、p-Smad2/3were no difference between the Han nationality and Uyghur nationality with pancreatic cancer.Conclusion1. Increased expression of OCT4is correlated with differentiation of pancreatic cancer, and promotes growth and invasion of pancreatic cancer cells through AKT pathway, suggesting that OCT4may serve as a potential therapeutic target for the treatment of pancreatic cancer.2. PTTG1is highly expressed in human pancreatic cancer, and the positive expression of PTTG1was associated with the gender of cancer patients, and might represent a potential therapeutic target for treatment of pancreatic cancer.3. The positive expression of TAGLN2, TGFβRⅡ, p-Smad2/3was found associated with athological styles, TNM staging and perineural infiltration, did not correlate with their age, nationality, tumor size, tumor sites. The positive expression of TAGLN2has positive correlation with HGFβRⅡ、p-Smad2/3in pancreatic cancer tissues.