Expression of DAAM gene family in pancreatic cancer and its correlations with immune checkpoints
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摘要:
目的：探究蓬乱蛋白相关形态形成活化因子(dishevelled-associated activator of morphogenesis，DAAM)1和DAAM2在胰腺癌中的表达及临床意义。方法：购买胰腺癌组织芯片(HPanA120Su02)，包含66例癌及54例癌旁样本；采用免疫组织化学法检测 DAAM1、DAAM2 在胰腺癌及癌旁组织中的表达水平；下载癌症基因组图谱(the Cancer Genome Atlas，TCGA)数据库中 DAAM1、DAAM2及细胞程序性死亡配体1(programmed cell death ligand 1，PDL1)等免疫检查点分子的表达谱数据；采用t检验、 χ2 检验、log-rank检验、相关性分析等统计学方法分别分析DAAM1、DAAM2在癌与癌旁组织间表达的差异，二者的共表达关系，与临床病理参数、预后的关系，及其与免疫检查点分子表达的相关性。结果：相较于癌旁组织，DAAM1、DAAM2在胰腺癌中的表达均显著上调(P ＜ 0.001)，且胰腺癌组织中DAAM1与DAAM2的表达呈显著正相关(P ＜ 0.001)；DAAM1表达水平与肿瘤分化程度 (P=0.062)和患者生存状态(P=0.061)存在一定相关性，但差异无统计学意义，与其他临床病理参数无显著相关性(P ＞ 0.05)， 而DAAM2表达水平与各项临床病理参数均无显著相关性(P ＞ 0.05)；TCGA数据库中，DAAM1及DAAM2与PDL1等多个免疫检查点的表达呈显著正相关(P ＜ 0.001)。结论：DAAM1、DAAM2在胰腺癌中的表达显著上调，与PDL1等免疫检查点的表达呈正相关，可能是胰腺癌发生、发展及免疫逃避的关键调控因素。
Abstract:
Objective：To explore the expression and clinical significance of dishevelled-associated activator of morphogenesis 1 (DAAM1)and DAAM2 in pancreatic cancer. Methods：Pancreatic cancer tissue microarray(TMA，HPanA120Su02)was obtained from OUTDO BioTech(Shanghai)，including 66 tumor samples and 54 adjacent samples. Immunohistochemistry(IHC)was used to detect the expression levels of DAAM1 and DAAM2 in pancreatic cancer and para-tumor tissues. Expression profiles of DAAM1，DAAM2， PDL1 and other immune checkpoints were downloaded from the TCGA database. Statistical methods，such as t-test，χ2 test，log-rank test and correlation analysis，were used to analyze the differential expression of DAAM1 and DAAM2 between tumor and adjacent samples，the co -expression pattern of DAAM1 and DAAM2，and their association with clinicopathological parameters，prognosis and expression levels of immune checkpoints. Results：Compared with the adjacent tissues，the expression of DAAM1 and DAAM2 in pancreatic cancer were significantly upregulated(P ＜ 0.001)，and the expression levels of DAAM1 and DAAM2 in pancreatic cancer tissue were significantly positively correlated(P ＜ 0.001). There was marginally significant in the correlation between DAAM1 expression and tumor differentiation(P=0.062)and survival status(P=0.061)，but DAAM1 expression was not significantly correlated with other clinic-pathological parameters(P ＞ 0.05). However，DAAM2 expression was not related to any clinic-pathological parameters (P ＞ 0.05). In the TCGA database，DAAM1 and DAAM2 were positively correlated with the expression levels of multiple immune checkpoints(P ＜ 0.001). Conclusion：The expression of DAAM1 and DAAM2 are significantly upregulated in pancreatic cancer，and positively correlated with the expression levels of multiple immune checkpoints，which may be a critical regulatory factor for the oncogenesis，progression and immune evasion in pancreatic cancer.
