Synaptonemal complex protein 3 as a novel prognostic marker in early stage non-small cell lung cancer

Abstract

Synaptonemal complex protein 3 is a marker for cell transformation that has prognostic significance in various cancers. However, the prognostic significance of synaptonemal complex protein 3 has not been studied in non-small cell lung cancer. To investigate the potential correlation between synaptonemal complex protein 3 and various clinicopathologic parameters, we assessed the expression of synaptonemal complex protein 3 in archival tumor tissues from 258 patients with non-small cell lung cancer by immunohistochemical staining. By immunofluorescence, synaptonemal complex protein 3 was detected in both the cytoplasmic and nuclear fractions of NCI-H1299 cell. In tumor samples, synaptonemal complex protein 3 is detected as cytoplasmic expression pattern and observed in 50 clinical samples (19.4%) by immunohistochemical staining. Synaptonemal complex protein 3 expression was correlated with T status (P = .008), lymph node metastasis (P = .010), tumor types (P = .019), and pleural invasion (P = .005). In multivariate analysis of patients with early stage disease, increased synaptonemal complex protein 3 expression predicted worse overall survival in early stage (stage I and II) with pT1 status (P = .041). These results suggest that positive synaptonemal complex protein 3 expression is a portent of poor outcome and may be a potential biomarker in the early stages of the non-small cell lung cancer for survival and may provide clues in the identification of patients for adjuvant therapy.

Fig. 1

Synaptonemal complex protein 3 (SCP3) localization in a lung cancer cell line. (A) Nuclear and cytoplasmic fractions from H1299 cells were analyzed by western blot analysis using a SCP3 antibody. H2B and beta-actin were used as indexes for nuclear and cytoplasmic fractions, respectively. (B) Confocal fluorescent microscopy was used to further evaluate the distribution of SCP3 in H1299 cells 24 h after transfection of SCP3/EGFP DNA.

Fig. 2

Representative images of immunohistochemistry for synaptonemal complex protein 3 (SCP3). Negative - demonstrating a lack of SCP3 expression (A); Positive - cytoplasmic staining in adenocarcinoma (B) and squamous cell carcinoma (C). Boxed regions are displayed at high magnification in the bottom panel. All photomicrographs ×100.

Fig. 3

Kaplan-Meier survival analysis ofNSCLC according to SCP3 expression. (A) In early stage (≤ stage II) with pT1 group, patients with positive SCP3 expression (median survival, 87 months) showed significantly worse survival than those with negative SCP3 expression (median survival, 134 months). (B) Stage IA group with positive SCP3 expression (median survival, 87 months) had a significantly worse patients’ survival time than those with negative SCP3 expression (median survival, 138 months).