Accumulation of p62/SQSTM1 is associated with poor prognosis in patients with lung adenocarcinoma
Accumulation of p62/SQSTM1 is associated with poor prognosis in patients with lung adenocarcinoma
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DOI：
10.1111/j.1349-7006.2012.02216.x
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发表时间：
2012-04-01
期刊：
影响因子：
5.7
通讯作者：
Yamamoto, Masayuki
中科院分区：
文献类型：
--
作者：
Inoue, Daisuke;Suzuki, Takashi;Yamamoto, Masayuki
p62/SQSTM 1是自噬的选择性底物，并且在各种病理条件下已经观察到p62的异常积累。为了了解p62在非小细胞肺癌（NSCLC）中的作用，我们对一组有临床病理资料的患者进行了p62表达的免疫组化分析。由于对小鼠和人肝细胞癌的分析表明p62和NRF 2积累之间存在相关性，我们还检查了同一队列中NRF 2的表达。应用免疫组化方法检测109例NSCLC组织中NRF 2和p62的表达，其中腺癌72例，鳞癌31例，大细胞癌6例。NRF 2和p62的积累分别在34%和37%的NSCLC患者中检测到。p62和NRF 2的积累彼此之间没有相关性，但两者都与肺癌特异性生存率较差相关（NRF 2 P = 0.0003; p62 P = 0.0130）。NRF 2状态对NSCLC预后有影响，与组织学类型无关，但p62状态尤其在腺癌中有影响（P = 0.037）。多因素分析显示NRF 2和p62的阳性表达均是预测肺癌特异性生存率较低的独立因素（NRF 2 P < 0.0001，p62 P = 0.04）。NRF 2和p62是NSCLC的独立预后因子。p62状态对腺癌患者预后的影响是显著的，这表明腺癌和鳞状细胞癌之间癌症演变的分子机制不同。（Cancer Sci 2012; 103：760766）
p62/SQSTM1 is a selective substrate of autophagy, and aberrant accumulation of p62 has been observed in various pathological conditions. To understand the roles p62 plays in non-small-cell lung cancer (NSCLC), we carried out immunohistochemical analyses of p62 expression in a cohort of patients with annotated clinicopathological data. As analyses of murine and human hepatocellular carcinomas suggested a correlation between p62 and Nrf2 accumulations, we also examined NRF2 expression in the same cohort. The expression of NRF2 and p62 was examined by immunohistochemical methods in 109 NSCLC cases, which included patients with adenocarcinoma (n = 72), squamous cell carcinoma (n = 31), and large cell carcinoma (n = 6). Accumulation of NRF2 and p62 was detected in 34% and 37% of NSCLC patients, respectively. The accumulations of p62 and NRF2 did not correlate with each other, but both were associated with worse lung cancer-specific survival (P = 0.0003 for NRF2; P = 0.0130 for p62). NRF2 status had an impact on NSCLC prognosis irrespective of histology types, but p62 status did so particularly in adenocarcinoma (P = 0.037). Multivariate analysis indicated that positive immunoreactivities of NRF2 and p62 were both independent factors predicting worse lung cancer-specific survival (P < 0.0001 for NRF2 and P = 0.04 for p62). This study revealed that both NRF2 and p62 are independent prognostic factors for NSCLC. The prognostic impact of p62 status was pronounced in adenocarcinoma patients, suggesting that molecular mechanisms underlying cancer evolution differ between adenocarcinoma and squamous cell carcinoma. (Cancer Sci 2012; 103: 760766)