Yasuhiro Chikaishi1, Hidetaka Uramoto2, Yukiko Koyanagi1, Sohsuke Yamada3, Seiji Yano4, Fumihiro Tanaka1. 1. Second Department of Surgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan. 2. Second Department of Surgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan hidetaka@med.uoeh-u.ac.jp. 3. Departments of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan. 4. Division of Medical Oncology, Cancer Research Institute, Kanazawa University, Ishikawa, Japan.
Abstract
BACKGROUND: Postoperative recurrence is a significant problem associated with a poor prognosis. However, there is currently no consensus regarding biomarkers of recurrence. MATERIALS AND METHODS: We performed a microarray expression analysis using a combination of tumor tissues (n=2) and cell lines. We prioritized and validated candidate protein expression levels in the primary tumors. RESULTS: We prioritized 18 genes found to be up-regulated by more than four-fold in both A925LPE3 cell lines compared to the A925L cell line (lung adenocarcinoma) and in the cases of recurrence versus no recurrence, in order to find genes highly causative of metastasis. Among them, we selected transmembrane protease, serine 4 (TMPRSS4) and identified positive expression of TMPRSS4 in 93 (57.8%) patients. A significant negative association was observed only between the TMPRSS4 expression level and the N status. The univariate logistic regression models indicated that TMPRSS4 expression was an independent predictor of recurrence, as was the T and N status. CONCLUSION: TMPRSS4 expression is associated with postoperative recurrence. In addition, the current survival curves demonstrated that TMPRSS4 expression is associated with statistically significant differences in survival among patients with lung adenocarcinoma. TMPRSS4 staining can be used to predict the prognosis of such patients after surgery. Copyright
BACKGROUND: Postoperative recurrence is a significant problem associated with a poor prognosis. However, there is currently no consensus regarding biomarkers of recurrence. MATERIALS AND METHODS: We performed a microarray expression analysis using a combination of tumor tissues (n=2) and cell lines. We prioritized and validated candidate protein expression levels in the primary tumors. RESULTS: We prioritized 18 genes found to be up-regulated by more than four-fold in both A925LPE3 cell lines compared to the A925L cell line (lung adenocarcinoma) and in the cases of recurrence versus no recurrence, in order to find genes highly causative of metastasis. Among them, we selected transmembrane protease, serine 4 (TMPRSS4) and identified positive expression of TMPRSS4 in 93 (57.8%) patients. A significant negative association was observed only between the TMPRSS4 expression level and the N status. The univariate logistic regression models indicated that TMPRSS4 expression was an independent predictor of recurrence, as was the T and N status. CONCLUSION:TMPRSS4 expression is associated with postoperative recurrence. In addition, the current survival curves demonstrated that TMPRSS4 expression is associated with statistically significant differences in survival among patients with lung adenocarcinoma. TMPRSS4 staining can be used to predict the prognosis of such patients after surgery. Copyright
Authors: Allison S Cohen; Farah K Khalil; Eric A Welsh; Matthew B Schabath; Steven A Enkemann; Andrea Davis; Jun-Min Zhou; David C Boulware; Jongphil Kim; Eric B Haura; David L Morse Journal: Oncotarget Date: 2017-12-07