目的 探索层粘连蛋白α3亚基（LAMA3）对胰腺癌（PC）上皮间质转化（EMT）、侵袭和转移能力的影响。 方法 综合分析肿瘤和EMT相关数据库，筛选出与PC相关的EMT基因LAMA3。通过qRT-PCR和Western Blot检测LAMA3在PC组织和细胞系中的表达水平，免疫荧光确定LAMA3在PANC-1细胞中的定位，Transwell实验评估LAMA3对PC细胞侵袭和迁移能力的影响。计量资料组间比较采用t检验。 结果 利用TCGA数据库筛选出3个EMT相关PC致癌因子LAMA3、AREG和SDC1。LASSO-Cox回归模型显示，LAMA3对PC预后影响最为显著（风险评分=0.256 1×LAMA3+0.043 1×SDC1+0.071 4×AREG）。Cox回归模型和列线图显示，LAMA3的高表达是PC不良预后的独立危险因素（HR=1.32，95%CI：1.07～1.62，P<0.01）。实验结果显示，相对于正常胰腺组织，LAMA3在PC组织中的表达显著上调。相对于HPDE细胞株，LAMA3在PC细胞株AsPC-1、BxPC-3、PANC-1、MIA PaCa-2、SW1990中的表达均有不同程度的升高，其中在PANC-1细胞中的表达最高。富集分析表明，LAMA3与EMT、胶原代谢、细胞外基质降解、TGF-β通路和PI3K通路等生物过程和信号通路相关。敲低LAMA3后，N-Cadherin、Vimentin和Snail的表达水平下降，而E-Cadherin的表达水平上升。Transwell实验结果显示，LAMA3敲低后，PANC-1细胞的侵袭和迁移能力明显减弱。 结论 LAMA3在PC中高表达，促进PC细胞EMT、侵袭和迁移，可能是PC的新型诊断标志物和基因治疗靶点。

Objective To investigate the effect of laminin subunit α3 （LAMA3） on the epithelial-mesenchymal transition （EMT）， invasion， and metastasis abilities of pancreatic cancer （PC）. Methods A comprehensive analysis was performed for tumor- and EMT-related databases to identify the EMT genes associated with PC， especially LAMA3. The methods of qRT-PCR and Western blot were used to measure the expression level of LAMA3 in PC tissue and cell lines； immunofluorescence assay was used to determine the localization of LAMA3 in PANC-1 cells； Transwell assay was used to investigate the effect of LAMA3 on the invasion and migration abilities of PC cells. The t-test was used for comparison of continuous data between groups. Results The analysis of the TCGA database identified 3 EMT-related oncogenes for PC， i.e.， LAMA3， AREG， and SDC1. The LASSO-Cox regression model showed that LAMA3 had the most significant impact on the prognosis of PC （risk score=0.256 1×LAMA3+0.043 1×SDC1+0.071 4×AREG）. The Cox model and nomogram showed that the high expression of LAMA3 was an independent risk factor for the poor prognosis of PC （hazard ratio=1.32， 95% confidence interval： 1.07‍ ‍—‍ 1.62， P<0.01）. Experimental results showed that there was a significant increase in the expression of LAMA3 in pancreatic cancer tissue compared with the normal pancreatic tissue. Compared with the HPDE cell line， there were varying degrees of increase in the expression of LAMA3 in pancreatic cancer AsPC-1， BxPC-3， PANC-1， MIA PaCa-2， and SW1990 cell lines， with the highest expression level in PANC-1 cells. The enrichment analysis showed that LAMA3 was associated with the biological processes and signaling pathways such as EMT， collagen metabolism， extracellular matrix degradation， the TGF-β pathway， and the PI3K pathway. After the knockdown of LAMA3， there were significant reductions in the expression levels of N-Cadherin， Vimentin， and Snail， while there was a significant increase in the expression level of E-Cadherin. Transwell assay showed that there were significant reductions in the invasion and migration abilities of PANC-1 cells after the knockdown of LAMA3. Conclusion LAMA3 is highly expressed in PC and can promote the EMT， invasion， and migration of PC cells， and therefore， LAMA3 may be used as a novel diagnostic marker and a new therapeutic target for PC.