Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with poor prognosis. Gemcitabine remains an effective option for the majority of PDAC patients. Unfortunately, currently no reliable prognostic and predictive biomarkers of therapeutic response are available for the patients with PDAC. Laminin γ2 (LAMC2) is overexpressed in several cancers, and its high expression facilitates cancer development and chemoresistance. However, its functional role in PDAC remains unclear, and a better understanding of this will likely help improve the prognosis of PDAC patients. This study aimed to elucidate the clinical and biological role of LAMC2 in PDAC. We first analyzed the expression levels of LAMC2 by real-time reverse transcription PCR in a cohort of 114 PDAC patients. Interestingly, higher expression of LAMC2 significantly correlated with poor survival in PDAC cohort. In addition, elevated LAMC2 expression served as a potential prognostic marker for survival. Subsequently, functional characterization for the role of LAMC2 in PDAC was performed by small interfering RNA knockdown in pancreatic cancer (PC) cell lines. Interestingly, inhibition of LAMC2 in PC cells enhanced the gemcitabine sensitivity and induction of apoptosis. Moreover, it inhibited colony formation ability, migration and invasion potential. Furthermore, LAMC2 regulated the expression of epithelial-mesenchymal transition (EMT) phenotype. In addition, LAMC2 significantly correlated with genes associated with the expression of ATP-binding cassette (ABC) transporters in PC cells and PDAC patients. In conclusion, these results suggest that LAMC2 regulates gemcitabine sensitivity through EMT and ABC transporters in PDAC and may be a novel therapeutic target in PDAC patients.

中文翻译：

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LAMC2 通过调节胰腺导管腺癌中的 EMT 和 ATP 结合盒转运蛋白促进癌症进展和吉西他滨耐药。

胰腺导管腺癌（PDAC）是一种预后不良的侵袭性疾病。吉西他滨仍然是大多数 PDAC 患者的有效选择。不幸的是，目前没有可靠的预后和预测治疗反应的生物标志物可用于 PDAC 患者。层粘连蛋白 γ2 (LAMC2) 在几种癌症中过表达，其高表达促进癌症发展和化学抗性。然而，它在 PDAC 中的功能作用仍不清楚，更好地理解这一点可能有助于改善 PDAC 患者的预后。本研究旨在阐明 LAMC2 在 PDAC 中的临床和生物学作用。我们首先通过实时逆转录 PCR 在一组 114 名 PDAC 患者中分析了 LAMC2 的表达水平。有趣的是，LAMC2 的较高表达与 PDAC 队列中较差的存活率显着相关。此外，升高的 LAMC2 表达可作为生存的潜在预后标志物。随后，通过胰腺癌 (PC) 细胞系中的小干扰 RNA 敲低对 LAMC2 在 PDAC 中的作用进行了功能表征。有趣的是，抑制 PC 细胞中的 LAMC2 增强了吉西他滨的敏感性和细胞凋亡的诱导。此外，它抑制集落形成能力、迁移和入侵潜力。此外，LAMC2 调节上皮间质转化 (EMT) 表型的表达。此外，LAMC2 与与 PC 细胞和 PDAC 患者中 ATP 结合盒 (ABC) 转运蛋白表达相关的基因显着相关。综上所述，