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 established
Nestin knock-down cells and a newly established
Nestin-overexpressing cell line, we examined the relationship between
nestin expression and cell proliferation in vitro and in vivo and 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.