过度表达的 p-S6 与非小细胞肺癌的淋巴结转移相关，并预测不良预后。
Overexpressed p-S6 associates with lymph node metastasis and predicts poor prognosis in non-small cell lung cancer.
机构信息
Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China.
Cancer Research Institute of Central South University, Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Central South University, Changsha, 410011, Hunan, China.
出版信息
BMC Cancer. 2022 May 20;22(1):564. doi: 10.1186/s12885-022-09664-4.
BACKGROUND
Ribosomal protein S6 (S6), a downstream effect media of the AKT/mTOR pathway, not only is a part of 40S small subunit of eukaryotic ribosome, but also involves in protein synthesis and cell proliferation during cancer development.
METHODS
In present study, we explore the association between phosphorylated S6 (p-S6) protein expression and clinicopathological features as well as prognostic implications in NSCLC. P-S6 was detected in tissue microarrays (TMAs) containing 350 NSCLC, 53 non-cancerous lung tissues (Non-CLT), and 88 cases of matched metastatic lymph node lesions via immunohistochemistry (IHC). Transwell assays and wound healing assay were used to assess the effects of p-S6 inhibition on NSCLC cell metastasis.
RESULTS
The p-S6 expression in NSCLC was more evident than that in Non-CLT (p < 0.05). Compared to NSCLC patients who have no lymph node metastasis (LNM), those with LNM had higher p-S6 expression (p = 0.001). Regardless of lung squamous cell carcinoma (SCC) or adenocarcinoma (ADC), p-S6 was increased obviously in metastatic lymph nodes compared with matched primary cancers (p = 0.001, p = 0.022, respectively). Inhibition of p-S6 decreased the metastasis ability of NSCLC cells. In addition, p-S6 was an independent predicted marker for LNM in patients with NSCLC (p < 0.001). According to survival analysis, patients with highly expressed p-S6 had a lower survival rate compared with that with lower expression (p = 0.013). P-S6 is an unfavorable independent prognostic factor for NSCLC patients (p = 0.011).
CONCLUSION
Increased expression of p-S6 is not only a novel predictive biomarker of LNM but also poor prognosis in NSCLC.
背景
核糖体蛋白 S6（S6）是 AKT/mTOR 通路的下游效应介质，不仅是真核核糖体 40S 小亚基的一部分，而且在癌症发展过程中参与蛋白质合成和细胞增殖。
方法
本研究通过免疫组织化学（IHC）检测组织微阵列（TMA）中 350 例 NSCLC、53 例非癌性肺组织（Non-CLT）和 88 例匹配的转移性淋巴结病变中磷酸化 S6（p-S6）蛋白的表达与 NSCLC 的临床病理特征及预后的关系。Transwell 分析和划痕愈合实验用于评估 p-S6 抑制对 NSCLC 细胞转移的影响。
结果
与 Non-CLT 相比，NSCLC 中 p-S6 的表达更为明显（p<0.05）。与无淋巴结转移（LNM）的 NSCLC 患者相比，有 LNM 的患者 p-S6 表达更高（p=0.001）。无论肺鳞癌（SCC）还是腺癌（ADC），与匹配的原发性癌症相比，转移性淋巴结中 p-S6 均明显升高（p=0.001，p=0.022）。抑制 p-S6 降低了 NSCLC 细胞的转移能力。此外，p-S6 是 NSCLC 患者 LNM 的独立预测标志物（p<0.001）。根据生存分析，p-S6 高表达患者的生存率低于低表达患者（p=0.013）。p-S6 是 NSCLC 患者预后不良的独立预测因素（p=0.011）。
结论
p-S6 的表达增加不仅是 LNM 的新型预测生物标志物，也是 NSCLC 预后不良的独立预测因素。
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