FAIM2, as a novel diagnostic maker and a potential therapeutic target for small-cell lung cancer and atypical carcinoid.
Lung neuroendocrine (NE) tumors are a heterogeneous group of tumors arising from neuroendocrine cells that includes typical carcinoid, atypical carcinoid, small cell lung cancer (SCLC), and large cell NE cancer. The subtyping of NE tumors is based on the number of mitoses per high powered field and the presences of necrosis. However, the best diagnostic criteria to differentiate various subtypes of lung NE tumors remains controversial and few diagnostic markers distinguish typical and atypical carcinoid. In this study, we show that FAIM2, an inhibitory molecule in the Fas-apoptosis pathway, is significantly overexpressed in SCLC compared to non-small cell lung cancer. In addition, FAIM2 expression is significantly higher in atypical carcinoid than typical carcinoid. As atypical carcinoid has been shown to have worse clinical outcomes than typical carcinoid, our data suggests that FAIM2 may be a useful diagnostic marker for atypical carcinoid. Knockdown of FAIM2 expression increases Fas-induced apoptotic cell death in SCLC cells. Etoposide treatment combined with FAIM2 inhibition also shows modest but significant reduction of viable SCLC cells. Taken together, our results suggest that FAIM2 is a potential NE tumor marker with higher expression in atypical carcinoid and SCLC, and could be a new therapeutic target for SCLC.
Thoracic Oncology Laboratory, Department of Surgery, University of California San Francisco, San Francisco, CA, USA.|Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Hio Chung
HC
Kang
Thoracic Oncology Laboratory, Department of Surgery, University of California San Francisco, San Francisco, CA, USA.|Department of Thoracic and Cardiovascular Surgery, Kosin University College of Medicine, Busan, Republic of Korea.
Jong In
JI
Kim
Department of Pathology, Kosin University College of Medicine, Busan, Republic of Korea.
Hee Kyung
HK
Chang
Thoracic Oncology Laboratory, Department of Surgery, University of California San Francisco, San Francisco, CA, USA.
Gavitt
G
Woodard
Department of Internal Medicine, Kosin University College of Medicine, Busan, Republic of Korea.
Young Sik
YS
Choi
Laboratory of Cell Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
Ja-Lok
JL
Ku
Thoracic Oncology Laboratory, Department of Surgery, University of California San Francisco, San Francisco, CA, USA.|Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
David M
DM
Jablons
Thoracic Oncology Laboratory, Department of Surgery, University of California San Francisco, San Francisco, CA, USA.|Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Il-Jin
IJ
Kim
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