Expression And Clinical Characters Of Autophagy-related Protein Beclin1, LC3 And P62 In Advanced Pancreatic Cancer

Autophagy is one of the most important researches in recent years. It refers to cells digest and resolve the damaged organelles, protein, etc, by themselves in various ways in autophagy-lysosome. It is a kind of "self-digestion" in subcellular level.The basic level of autophagy is essential to cells’ growth and development, and performance of their biological functions. Through autophagy, cells could maintain a steady state, which is helpful for them to better adapt to all kinds of stress, and achieve self-renewal. And when cells can’t recover themselves after much damage, the autophagic death starts to work. Therefore autophagy is also known as typeⅡprogrammed cell death(PCD). The changes of autophagy level can be found in numerous human tumor. Cell autophagy is a complex process. Many signal transduction pathways involved in the regulation of autophagy level. The cell autophagy can be induced under a variety of conditions, such as growth factor, amino acids incells, glucose levels, DNA damage, and oxygen free radicals, they all could induce the change of cell autophagy level. Beclin1 played an important role at the launch stage of autophagy. Beclin1, P13K(h VPS34), and Atg14 forms atripolymer, and it constantly collect the proteins related to autophagy, and mediatethe start of autophagy. With the action of Atg4, LC3 precursor is processed into soluble LC3-Ⅰ.And the latter links to phosphatidylethanolamine(PE) becomes fat soluble LC3-Ⅱ– PE under the action of Atg7(E1 sample) and Atg3(E2 sample). The fat soluble LC3-Ⅱ– PE will not stop working for the extension of autophagy-lysosome membrane until the autophagy-lysosome is formed. The P62 located in the cytoplasm combines with ubiquitin protein, then the P62 protein combines with LC3- II protein, then some complexes is got. And the complexes will eventually be degraded in the lysosome. In the process of autophagy, P62 is constantly consumed.These three proteins can be used as the markers of autophagy level. As known as a highly invasive malignant tumor, the pathogenesis of pancreatic cancer is concealed, and the majority of patients during the diagnosis has been advanced, and 5-year survival rate is only 1-4%, as well as with poorprognosis. However, the autophagy proteins’ researches involve in pancreatic cancer is relatively less at present.Aim To investigate the expressions of Beclin1, LC3 and P62 in pancreatic cancer and analyze the correlation of Beclin1, LC3 and P62 expression with clinical and pathological parameters of pancreatic cancer.Methods Immunohistochemistry was used to detect the expressions of Beclin1, LC3 and P62 proteins in 64 pancreatic cancer specimens and correlated tumor-free tissues. SPSS17.0 statistical package is used to analyze all the datas, and statistical methods contain the Chi-square test and Spearman correlation ananlysis, and the difference is statistically significant when P<0.05.Results The results of immunohistochemistary showed that the rates of Beclin 1 positive expression in pancreatic cancer and corresponding adjacent noncancerous tissues were 35.9%(23/64), 90.6%(58/64), P<0.05.the rates of LC3 were 34.4%(22/64),75%(48/64), P<0.05. the rates of P62 were75%(48/64), 46.9%(30/64) P<0.05, The correlation coefficient between Beclin1 and LC3 in pancreatic cancer is 0.572 P<0.05). The expression of Beclin 1 in pancreatic cancer were associated with differentiation degree and disease stage(P<0.05), the lower expression of Beclin 1, LC3 and higher expression of P62 in pancreatic cancer have no significant associated with gender depth of tumor invasion, lymph node metastases(P>0.05).Conclusion The desregulation of Beclin1, LC3 and P62 may be related to the pathogenesis of pancreatic cancer.