Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215006, China.
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wannan Medical College, Wuhu 241000, China.
Anticancer Agents Med Chem. 2019;19(11):1359-1367. doi: 10.2174/1871520619666190416110851.
Gastric Cancer (GC) is a frequently common malignancy. Recent studies have reported Rab1A as an activator of mTORC1, and the mTOR1 pathway is involved in regulating Gli1 expression in several cancers. Only a few studies have been performed to explore the relationship between Rab1A and p-S6K/Gli1in GC.
Immunohistochemistry (IHC) was performed to explore the association of Rab1A/p-S6K/Gli1 expression and prognosis in 117 GC tissue samples and adjacent normal tissues.
Our results indicated that Rab1A/p-S6K/Gli1 was significantly overexpressed in GC tissues. High expression of Rab1A was closely related to the tumor size and the depth of tumor invasion. In addition, Rab1A expression was closely related with p-S6K/Gli1 expression in GC, and high level of Rab1A/p-S6K/Gli1 caused worse prognosis of GC patients. The univariate and multivariate analysis indicated that the expression of Rab1A was an independent prognostic factor. Moreover, both high Rab1A and p-S6K expression led to a worse prognosis when compared to a single positive expression as well as both high Rab1A/Gli1 expression also led to a worse prognosis than the single positive expression of Rab1A/Gli1. Strikingly, the overexpression of p-S6K also led to a worse prognosis in Rab1A positive patients, as did Gli1.
Our results indicate that Rab1A/mTOR/S6K/Gli1 axis played a crucial role in GC, which may provide a novel field on targeted therapy of GC, especially for mTORC1-targeted therapy-resistant cancers.
胃癌（GC）是一种常见的恶性肿瘤。最近的研究报道 Rab1A 是 mTORC1 的激活剂，mTOR 通路参与调节几种癌症中的 Gli1 表达。只有少数研究探讨了 Rab1A 与 p-S6K/Gli1 在 GC 中的关系。
免疫组织化学（IHC）用于探索 117 例 GC 组织样本和相邻正常组织中 Rab1A/p-S6K/Gli1 表达与预后的关系。
我们的结果表明，Rab1A/p-S6K/Gli1 在 GC 组织中明显过表达。Rab1A 的高表达与肿瘤大小和肿瘤浸润深度密切相关。此外，Rab1A 在 GC 中与 p-S6K/Gli1 的表达密切相关，Rab1A/p-S6K/Gli1 高水平与 GC 患者的预后不良密切相关。单因素和多因素分析表明，Rab1A 的表达是独立的预后因素。此外，与单个阳性表达相比，Rab1A 和 p-S6K 的高表达导致预后更差，Rab1A/Gli1 的高表达也导致预后更差比 Rab1A/Gli1 的单一阳性表达更差。值得注意的是，p-S6K 的过度表达也导致 Rab1A 阳性患者的预后更差，Gli1 也是如此。
我们的研究结果表明，Rab1A/mTOR/S6K/Gli1 轴在 GC 中发挥了重要作用，这可能为 GC 的靶向治疗提供了一个新的领域，特别是对于 mTORC1 靶向治疗耐药的癌症。
