Sonic Hedgehog Pathway as the Prognostic Marker in Patients with Extensive Stage Small Cell Lung Cancer
10.3349/ymj.2019.60.10.898
- Author:
Seungtaek LIM
1
;
Sun Min LIM
;
Min Ju KIM
;
Shin Young PARK
;
Joo Hang KIM
Author Information
1. Department of Hemato-Oncology, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Korea.
- Publication Type:Original Article
- Keywords:
Small cell lung cancer;
prognostic factors;
hedgehog proteins;
drug therapy
- MeSH:
Carcinogenesis;
Disease-Free Survival;
Drug Therapy;
Hedgehog Proteins;
Hedgehogs;
Humans;
Lung Neoplasms;
Multivariate Analysis;
Oncogenes;
Prognosis;
Repression, Psychology;
Retrospective Studies;
Small Cell Lung Carcinoma;
Zinc Fingers
- From:Yonsei Medical Journal
2019;60(10):898-904
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE: Sonic hedgehog (Shh) signaling pathway is known to play a crucial role in carcinogenesis in various malignancies, including lung cancer regarding tumorigenesis, angiogenesis, and cellular differentiation. The aim of this study was to investigate the value of components of Shh pathway as a prognostic marker in extensive stage small cell lung cancer (ES-SCLC) patients. MATERIALS AND METHODS: We retrospectively analyzed data of 36 patients who were diagnosed with ES-SCLC between 2008 and 2012 at a single center. We performed immuo-histochemistry for glioma-associated oncogene homolog zinc finger protein 1 (Gli1), patched, Shh, and Ptch-mediated repression of smoothened (Smo) proteins using formalin-fixed, paraffin-embedded tissue derived from primary tumors. We then conducted survival analysis to evaluate the prognostic impact of these markers. RESULTS: All 36 patients received platinum-based doublet chemotherapy. The median progression free survival and median overall survival were 6.9 months [95% confidence interval (CI), 6.5–7.3] and 11.7 months (95% CI, 9.1–14.3), respectively. The overall response rate was 84%. Of the 36 tissue specimens examined, over-expression of Gli1, Patched, Shh, and Smo was found in 12 (33.3%), five (13.9%), five (13.9%), and six (16.7%) cases, respectively. We found that high expression of Shh was associated with worse progression free survival (6.3 vs. 7.6 months, p=0.005) and overall survival (9.2 vs. 12.0 months, p=0.039) by both univariate and multivariate analyses, whereas other markers were not related to patient prognosis. CONCLUSION: A high proportion of small cell lung cancer tumors express proteins related to Shh pathway, and over-expression of Shh is correlated with poor prognosis.
