PO.CL01.17 · 临床研究
STING表达在可切除肺腺癌患者中的预后意义
Prognostic significance of STING expression in patients with resected lung adenocarcinoma
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：肺癌是全球癌症死亡的首要原因。肿瘤复发是手术切除后治疗失败最常见的原因。STING（干扰素[IFN]基因刺激因子）是一种负责调控针对泄漏的自身或非自身DNA的抗癌免疫反应的蛋白。近期研究在动物模型中表明，敲除STING和cGAS的表达会导致对PD-L1检查点治疗无反应。因此，STING和cGAS被认为对PD-1/PD-L1检查点抑制的抗肿瘤反应至关重要。多项研究报道，在肝细胞癌、胃癌和结直肠癌以及黑色素瘤中，肿瘤内STING表达下降。STING在肿瘤进展过程中常常丢失，且STING/cGAS的丢失与不良生存相关。STING表达在可切除肺腺癌患者中的预后价值尚未得到充分证实。
方法：本研究共纳入68例可切除肺腺癌患者。通过免疫组化测定肿瘤标本中的STING表达。研究了STING表达的预后价值及其与临床病理变量的关系。我们筛查了多种肺癌细胞系中STING的表达。将在合适的肺癌细胞系中进行STING敲低或转染。将进行蛋白质印迹（Western blot）分析以检测STING、E-cadherin和vimentin的表达。
结果：在68例肺肿瘤样本中，45例（66.2%）显示STING高表达。优势模式组（贴壁/腺泡/乳头 对比 微乳头/实体）（P = 0.662）与STING表达无显著相关。单因素分析表明，STING高表达（HR，0.158；95% CI，0.032 至 0.787；P = 0.024）是较好无病生存（DFS）的显著预后因素。在多因素分析中，优势模式组（贴壁/腺泡/乳头 对比 微乳头/实体）（HR，5.764；95% CI，1.054 至 31.537；P = 0.043）是DFS的显著预后因素。STING高表达（HR，0.073；95% CI，0.009 至 0.617；P = 0.016）同样是较好DFS的显著预后因素。
结论：STING高表达是手术切除肺腺癌患者较好DFS的显著预后因素。这一信息有助于对肺腺癌切除术后的复发高危患者进行分层。
查看英文原文 English abstract
Background: Lung cancer is the leading cause of cancer death worldwide. Tumor recurrence is the most common cause of treatment failure after surgical resection. STING (Stimulator of Interferon [IFN] Genes) is a protein responsible for controlling anticancer immune responses to leaked self‐ or non‐self DNA. Recent studies have shown in animal models that knocking out STING and cGAS expression results in a nonresponse to PD‐L1 checkpoint therapy. STING and cGAS are thus thought to be essential for the antitumor response of PD‐1/PD‐L1 checkpoint inhibition. Several studies have reported that STING expression was decreased in tumor in hepatocellular, gastric and colorectal cancer, and in melanoma. STING is frequently lost during tumor progression, and loss of STING/cGAS correlates with poor survival. The prognostic value of STING expression in patients with resected lung adenocarcinoma has not been well demonstrated.
Methods: A total of 68 patients with resected lung adenocarcinoma were included in the study. STING expression was determined by immunohistochemistry in tumor specimens. The prognostic value of STING expression and its relationship with clinicopathological variables were investigated. We have screened the expression of STING in several lung cancer cell lines. STING knockdown or transfection will be performed in suitable lung cancer cell lines. Western blotting analysis will be performed to demonstrated STING, E-cadherin and vimentin expression.
Results: High STING expression was shown in 45 (66.2%) of the 68 lung tumor samples. Predominant pattern group (lepidic/acinar/papillary vs. micropapillary/solid) ( P = 0.662) was not significantly associated with STING expression. Univariate analysis indicated that high STING expression (HR, 0.158; 95% CI, 0.032 to 0.787; P = 0.024) was a significant prognostic factor for better disease-free survival (DFS). In multivariate analysis, predominant pattern group (lepidic/acinar/papillary vs. micropapillary/solid) (HR, 5.764; 95% CI, 1.054 to 31.537; P = 0.043) was a significant prognostic factor for DFS. High STING expression (HR, 0.073; 95% CI, 0.009 to 0.617; P = 0.016) was also a significant prognostic factor for better DFS.
Conclusions: High STING expression was a significant prognostic factor for better DFS in patients with surgical resected lung adenocarcinoma. This information is useful to stratify high-risk patients of recurrence after resection of lung adenocarcinoma.
利益披露 Disclosure
J. Hung, None..
Y. Kao, None.