Oncotarget

Research Papers:

Expression of Notch1 and Numb in small cell lung cancer

Hajime Kikuchi _, Jun Sakakibara-Konishi, Megumi Furuta, Hiroshi Yokouchi, Hiroshi Nishihara, Shigeo Yamazaki, Hidetaka Uramoto, Fumihiro Tanaka, Masao Harada, Kenji Akie, Fumiko Sugaya, Yuka Fujita, Kei Takamura, Tetsuya Kojima, Toshiyuki Harada, Mitsunori Higuchi, Osamu Honjo, Yoshinori Minami, Naomi Watanabe, Satoshi Oizumi, Hiroyuki Suzuki, Takashi Ishida, Hirotoshi Dosaka-Akita, Hiroshi Isobe, Mitsuru Munakata and Masaharu Nishimura

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Oncotarget. 2017; 8:10348-10358. https://doi.org/10.18632/oncotarget.14411

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Abstract

Hajime Kikuchi1, Jun Sakakibara-Konishi1, Megumi Furuta1, Hiroshi Yokouchi2, Hiroshi Nishihara3, Shigeo Yamazaki4, Hidetaka Uramoto5,6, Fumihiro Tanaka5, Masao Harada7, Kenji Akie8, Fumiko Sugaya9, Yuka Fujita10, Kei Takamura11, Tetsuya Kojima12, Toshiyuki Harada13, Mitsunori Higuchi14,15, Osamu Honjo9,16, Yoshinori Minami17, Naomi Watanabe18, Satoshi Oizumi1,7, Hiroyuki Suzuki15, Takashi Ishida2,19, Hirotoshi Dosaka-Akita20, Hiroshi Isobe12, Mitsuru Munakata2, Masaharu Nishimura6

 1Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan

 2Department of Pulmonary Medicine, Fukushima Medical University, Fukushima, Japan

 3Department of Translational Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Japan

 4Department of Thoracic Surgery, Keiyukai Sapporo Hospital, Sapporo, Japan

 5Department of Surgery, University of Occupational and Environmental Health, Kita-kyushu, Japan

 6Department of Thoracic Surgery, Kanazawa Medical University, Uchinada, Japan

 7Department of Respiratory Medicine, National Hospital Organization Hokkaido Cancer Center, Sapporo, Japan

 8Department of Respiratory Disease, Sapporo City General Hospital, Sapporo, Japan

 9Department of Respiratory Medicine, Teine Keijinkai Hospital, Sapporo, Japan

10Department of Respiratory Medicine, National Hospital Organization Asahikawa Medical Center, Asahikawa, Japan

11Department of Medicine, Obihiro Kosei Hospital, Obihiro, Japan

12Department of Medical Oncology, KKR Sapporo Medical Center, Sapporo, Japan

13Center for Respiratory Diseases, JCHO Hokkaido Hospital, Sapporo, Japan

14Department of Thoracic Surgery, Fukushima Red Cross Hospital, Fukushima, Japan

15Department of Thoracic Surgery, Fukushima Medical University, Fukushima, Japan

16Department of Respiratory Medicine, Sapporo-Kosei General Hospital, Sapporo, Japan

17Respiratory Center, Asahikawa Medical University, Asahikawa, Japan

18Department of Internal Medicine, Sunagawa City Medical Center, Sunagawa, Japan

19Clinical Oncology Center, Fukushima Medical University Hospital, Fukushima, Japan

20Department of Medical Oncology, Hokkaido University Graduate School of Medicine, Sapporo, Japan

Correspondence to:

Jun Sakakibara-Konishi, email: konishj@med.hokudai.ac.jp

Keywords: small cell lung cancer, Notch1, Numb, immunohistochemistry, surgery

Received: August 04, 2016     Accepted: December 12, 2016     Published: January 02, 2017

ABSTRACT

Notch signaling in tumorigenesis functions as an oncogene or tumor suppressor according to the type of malignancy. Numb represses intracellular Notch signaling. Previous studies have demonstrated that Notch signaling suppresses the proliferation of small cell lung cancer (SCLC) cell lines. However, in SCLC, the association between Notch1 and Numb expression and clinicopathological factors or prognosis has remained unclear. In this study, we evaluated the expression of Notch1 and Numb in SCLC. We immunohistochemically assessed 125 SCLCs that were surgically resected at 16 institutions participating in either the Hokkaido Lung Cancer Clinical Study Group Trial (HOT) or the Fukushima Investigative Group for Healing Thoracic Malignancy (FIGHT) between 2003 and 2013. Correlations between Notch1 or Numb expression and various clinicopathological features were evaluated. Notch1 expression was associated with ECOG performance status. Numb expression was associated with age, sex, and pathological histology (SCLC or Combined SCLC). Analysis of cellular biological expression did not demonstrate a significant correlation between the expression of Notch1 and of Numb. Multivariate Cox regression analysis showed that high Notch1 expression was an independent favorable prognostic factor for SCLC(hazard ratio = 0.503, P = 0.023). High Notch1 expression, but not Numb expression, is associated with favorable prognosis in SCLC.


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