Nestin Expression Affects Resistance to Chemotherapy and Clinical Outcome in Small Cell Lung Cancer
Nestin Expression Affects Resistance to Chemotherapy and Clinical Outcome in Small Cell Lung Cancer
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DOI：
10.3389/fonc.2020.01367
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发表时间：
2020-08-06
影响因子：
4.7
通讯作者：
Niimi, Akio
中科院分区：
文献类型：
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作者：
Sone, Kazuki;Maeno, Ken;Niimi, Akio
目的：小细胞肺癌（small cell lung cancer，SCLC）是一种侵袭性强、转移性高的肺癌亚型.巢蛋白是中间丝蛋白家族的成员，是神经祖细胞和干细胞的潜在增殖和多能性标志物。巢蛋白的异常表达与包括非小细胞肺癌在内的不同癌症的不良预后有关。然而，巢蛋白表达与SCLC的临床病理特征或预后之间的关系仍不清楚。本研究探讨巢蛋白表达是否与小细胞肺癌的恶性特征和临床结局相关。材料和方法：利用先前建立的Nestin敲低细胞和新建立的Nestin过表达细胞系，我们研究了Nestin表达与体外细胞增殖和体内细胞增殖以及化疗敏感性之间的关系。我们还分析了巢蛋白在三种耐药肺癌细胞系中的表达。此外，我们检查了84例小细胞肺癌患者的样本（16例手术切除，68例活检），并对巢蛋白表达进行了化学分析。结果：Nestin表达与细胞增殖呈正相关，与化疗敏感性呈负相关。耐药细胞系中巢蛋白的表达与其亲本细胞相比上调。84例小细胞肺癌中，24例（28.6%）nestin阳性。巢蛋白阳性率在手术组高于活检组。巢蛋白阳性和阴性患者在一线化疗后的缓解率（RR）或无进展生存期（PFS）无显著差异。然而，巢蛋白阳性表达与二线化疗后较短的PFS相关（中位PFS：巢蛋白阳性，81天vs.巢蛋白阴性，117天;P= 0.029）。结论：巢蛋白表达可能与小细胞肺癌的恶性表型及预后有关。
Objectives:Small cell lung cancer (SCLC) is an aggressive and highly metastatic lung cancer subtype. Nestin is a member of the intermediate filament family and serves as a potential proliferative and multipotency marker in neural progenitor and stem cells. Aberrant expression of nestin is linked to poor prognosis in different cancers, including non-small cell lung cancer. However, the association between nestin expression and clinicopathological feature or prognosis has remained unclear for SCLC. This study examined whether nestin expression was associated with malignant features and clinical outcomes in SCLC. Materials and Methods:Using previously establishedNestinknock-down cells and a newly establishedNestin-overexpressing cell line, we examined the relationship between nestin expression and cell proliferationin vitroandin vivoand chemosensitivity. We also analyzed nestin expression in three drug-resistant lung cancer cell lines. Furthermore, we examined samples from 84 SCLC patients (16 patients with surgical resection, and 68 patients with biopsy), and immunohistochemically analyzed nestin expression. Results:Nestin expression correlated positively with cell proliferation, but negatively with chemosensitivity. Nestin expression in drug-resistant cell lines was upregulated compared to their parental cells. Among the 84 SCLC patients, 24 patients (28.6%) showed nestin-positive tumor. Nestin-positive ratio tended to be higher in operated patients than in biopsied patients. Nestin-positive and -negative patients showed no significant differences in response rate (RR) or progression-free survival (PFS) following first-line chemotherapy. However, positive expression of nestin was associated with shorter PFS following second-line chemotherapy (median PFS: nestin-positive, 81 days vs. nestin-negative, 117 days;P= 0.029). Conclusions:Nestin expression may be associated with malignant phenotype and worse outcome in SCLC patients.