Department of Medical Oncology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, Shandong, China.
Department of Thoracic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266003, Shandong, China.
BMC Cancer. 2021 Sep 21;21(1):1043. doi: 10.1186/s12885-021-08777-6.
Clinical options for lung squamous carcinoma (LUSC) are still quite limited. Carcinogenesis is an exceedingly complicated process involving multi-level dysregulations. Therefore, only looking into one layer of genomic dysregulation is far from sufficient.
We identified differentially expressed genes with consistent upstream genetic or epigenetic dysregulations in LUSC. Random walk was adopted to identify genes significantly affected by upstream abnormalities. Expression differentiation and survival analysis were conducted for these significant genes, respectively. Prognostic power of selected gene was also tested in 102 male LUSC samples through immunohistochemistry assay.
Twelve genes were successfully retrieved from biological network, including ERα (ESRS1), EGFR, AR, ATXN1, MAPK3, PRKACA, PRKCA, SMAD4, TP53, TRAF2, UBQLN4 and YWHAG, which were closely related to sex hormone signaling pathway. Survival analysis in public datasets indicated ERα was significantly associated with a poor overall survival (OS) in male LUSC. The result of our immunohistochemistry assay also demonstrated this correlation using R0 resected tumors (n = 102, HR: 2.152, 95% CI: 1.089-4.255, p = 0.024). Although disease-free survival (DFS) difference was non-significant (n = 102, p = 0.12), the tendency of distinction was straight-forward. Cox analysis indicated ERα was the only independent prognostic factor for male patients' OS after R0 resection (HR = 2.152, p = 0.037).
ERα was significantly related to a poor prognosis in LUSC, especially for male patients after radical surgery, confirmed by our immunohistochemistry data.
肺鳞状细胞癌（LUSC）的临床选择仍然相当有限。癌症发生是一个极其复杂的过程，涉及多层次的失调。因此，仅研究一层基因组失调是远远不够的。
我们鉴定了在 LUSC 中具有一致的上游遗传或表观遗传失调的差异表达基因。采用随机游走方法识别受上游异常显著影响的基因。分别对这些显著基因进行表达差异和生存分析。通过免疫组织化学检测在 102 例男性 LUSC 样本中也测试了选定基因的预后能力。
从生物网络中成功检索到 12 个基因，包括 ERα（ESRS1）、EGFR、AR、ATXN1、MAPK3、PRKACA、PRKCA、SMAD4、TP53、TRAF2、UBQLN4 和 YWHAG，它们与性激素信号通路密切相关。公共数据集的生存分析表明，ERα 与男性 LUSC 的总生存期（OS）显著相关。我们的免疫组织化学检测结果也使用 R0 切除肿瘤（n=102，HR：2.152，95%CI：1.089-4.255，p=0.024）证实了这种相关性。尽管无病生存期（DFS）差异无统计学意义（n=102，p=0.12），但这种差异趋势是显而易见的。Cox 分析表明，ERα 是 R0 切除后男性患者 OS 的唯一独立预后因素（HR=2.152，p=0.037）。
ERα 与 LUSC 的不良预后显著相关，特别是在根治性手术后的男性患者中，我们的免疫组织化学数据对此进行了证实。
