Neuro-Oncology, Nov 2011
BACKGROUND: Glioblastomas, the most common primary brain tumors in adults, still continue to have a predominantly fatal outcome. We previously cloned NPAS3 (neuronal PAS 3), a gene which is among the largest genes in the human genome and encodes a transcription factor. We recently discovered NPAS3 drives the progression of malignant astrocytomas as a tumor suppressor, by modulating the cell cycle, proliferation, apoptosis, and cell migration/invasion, and has a further influence on angiogenesis. In human glioblastoma surgical specimens, up to 75% demonstrate aberrant NPAS3 protein expression. In this study, we evaluated the expression of NPAS3 in the overall survival of patients diagnosed with glioblastomas. METHODS AND RESULTS: We examined a panel of glioblastomas from 77 postoperative patients who had total resection of the tumor. Postoperative patients were treated by standard adjuvant radiation therapy (60 Gy, 6 to 7 weeks) combined with chemotherapy, with a study follow-up not exceeding 30 months. Among the glioblastomas, 28 had absent, 18 had elevated, and 31 had normal NPAS3 expression. There were 54 males and 23 females in this study, with a median age of 59 years. In this study, patients with glioblastomas who had absent NPAS3 expression were identified as having the poorest overall survival compared with patients with glioblastomas who had normal or elevated NPAS3 expression (log-rank P value <0.001). Such a trend is still maintained even when patients are stratified among different age groups (<60 and >60 years). However, no significant difference in overall survival among patients with glioblastomas who had either normal or elevated NPAS3 expression was noted (log-rank P value >0.05). Likewise, no significant difference in gender versus overall survival noted. CONCLUSION: Our findings are of clinical importance by demonstrating that NPAS3 is an informative negative prognostic survival marker in patients with glioblastomas.
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Frederico Moriera, Kelvin So, Peter Gould, Deepak Kamnasaran, Randy L. Jensen, Ibrahim Hussain, David H. Gutmann, Daniel Gorovets, Edward R. Kastenhuber, Elena Pentsova, Lakshmi Nayak, Jason T. Huse, Martin J. van den Bent, Lonneke A. Gravendeel, Thierry Gorlia, Johan M. Kros, Pieter Wesseling, Johannes Teepen, Ahmed Idbaih, Marc Sanson, Peter A Sillesvis Smitt, Pim J. French, Wei Zhang, Jing Zhang, Katherine Hoadley, Bob Carter, Shouwei Li, Chunsheng Kang, Yongping You, Chuanlu Jiang, Sonya Song, Tao Jiang, Clark Chen, Christiane Grimm, Markus Weiler, Rainer Claus, Dieter Weichenhan, Christian Hartmann, Christoph Plass, Michael Weller, Wolfgang Wick, Robert B. Jenkins, Hugues Sicotte, Yuanyuan Xiao, Brooke L. Fridley, Paul A. Decker, Matthew L. Kosel, Thomas M. Kollmeyer, Stephanie R. Fink, Amanda L. Rynearson, Terri Rice, Lucie S. McCoy, Ivan Smirnov, Tarik Tehan, Helen M. Hansen, Joseph S. Patoka, Michael D. Prados, Susan M. Chang, Mitchel S. Berger, Daniel H. Lachance, John K. Wiencke, Joseph L. Wiemels, Margaret R. Wrensch, Melanie Hayden Gephart, Eunice Lee, Sofia Kyriazopoulou-Panagiotopoulou, Ljiljana Milenkovic, Xu Xun, Yong Hou, Wu Kui, Michael Edwards, Serafim Batzoglou, Wang Jun, Matthew Scott, Jennifer E. Hobbs, Jeremiah Tipton, Tom Zhou, Neil L. Kelleher, James P. Chandler, Johannes Schwarzenberg, Johannes Czernin, Timothy Cloughesy, Benjamin Ellingson, Cheri Geist, Mike Phelps, Wei Chen, Mitsutoshi Nakada, Yutaka Hayashi, Wataru Obuchi, Sumio Ohtsuki, Takuya Watanabe, Chiemi Ikeda, Kouichi Misaki, Daisuke Kita, Yasuhiko Hayashi, Naoyuki Uchiyama, Tetsuya Terasaki, Jun-ichiro Hamada, Lotte Hiddingh, Bastiaan Tops, Esther Hulleman, Gert-Jan L. Kaspers, W. Peter Vandertop, Pieter Wesseling, David P. Noske, Tom Wurdinger, Judith W. Jeuken, Alfred Pokmeng See, Taeyoung Hwang, Dongjin Shin, Joo Heon Shin, Yuan Gao, Michael Lim, Markus Hutterer, Medinger Michael, Untergasser Gerold, Steinlechner Karin, Gstrein Ingrid, Deisenhammer Florian, Muigg Armin, Trinka Eugen, Gunsilius Eberhard, Stockhammer Günther, Robert W. Cook, Kristen Oelschlager, Hatice Sevim, Liping Chung, Helen T. Wheeler, Robert C. Baxter, Kerrie L. McDonald, Abhishek Chaturbedi, Liping Yu, Yi-Hong Zhou, Abhishek Chaturbedi, Anthony Wong, Remi Fatuyi, Mark E. Linskey, Yi-Hong Zhou, Iris Lavon, Tal Shahar, Daniel Zrihan, Avital Granit, Zvi Ram, Tali Siegal, Daniel J. Brat, Lee A. Cooper, David A. Gutman, Candace S. Chisolm, Christina Appin, Jun Kong, Tahsin Kurc, Erwin G. Van Meir, Joel H. Saltz, Carlos S. Moreno, Hazem J. Abuhusain, Kerrie L. McDonald, Anthony S. Don, Raman P. Nagarajan, Brett E. Johnson, Adam B. Olshen, Ivan Smirnov, Mingchao Xie, Jiexun Wang, Vasavi Sundaram, Pamela Paris, Ting Wang, Joseph F. Costello, Angelique E. Sijben, Sandra H. Boots-Sprenger, Jeroen Boogaarts, Jos Rijntjes, Johanna M. Geitenbeek, Job van der Palen, Hans J. Bernsen, Pieter Wesseling, Judith W. Jeuken, Oliver Schnell, S.A. Adam, Sabina Eigenbrod, Hans A. Kretzschmar, Jörg-Christian Tonn, Ulrich Schüller, Johannes Schwarzenberg, Timothy Cloughesy, Johannes Czernin, Cheri Geist, Mike Phelps, Wei Chen, Paul W. Sperduto, Norbert Kased, David Roberge, Zhiyuan Xu, Ryan Shanley, Xianghua Luo, Penny K. Sneed, Samuel T. Chao, Robert J. Weil, John Suh, Amit Bhatt, Ashley W. Jensen, Paul D. Brown, Helen A. Shih, John Kirkpatrick, Laurie E. Gaspar, John B. Fiveash, Veronica Chiang, Jonathan P. Knisely, Christina M. Sperduto, Nancy Lin, Minesh P. Mehta, Madan M. Kwatra, Tara M. Porter, Kristine E. Brown, James E. Herndon, Darell D. Bigner, Rikke H. Dahlrot, Bjarne W. Kristensen, Steinbjørn Hansen, Erik P. Sulman, Daniel P. Cahill, Meihau Wang, Minhee Won, Monika E. Hegi, Minesh P. Mehta, Ken D. Aldape, Mark R. Gilbert, Emad Seyed Sadr, Alain Tessier, Mohamed Seyed Sadr, Jad Alshami, Carmen Sabau, Rolando Del Maestro, Maxwell L. Neal, Russell Rockne, Andrew D. Trister, Kristin R. Swanson, Sanaz Maleki, Michael Back, Michael Buckland, David Brazier, Kerrie McDonald, Raymond Cook, Nicole Parker, Helen Wheeler, Llewellyn Jalbert, Adam Elkhaled, Joanna J. Phillips, Hikari A. Yoshihara, Rupa Parvataneni, Radhika Srinivasan, Gabriela Bourne, Susan M. Chang, Soonmee Cha, Sarah J. Nelson, Kenneth D. Aldape, Mark Gilbert, Daniel Cahill, Meihua Wang, Minhee Won, Monika Hegi, Howard Colman, Minesh Mehta, Erik Sulman, Adam Elkhaled, Llewellyn Jalbert, Alexandra Constantin, Joanna Phillips, Hikari Yoshihara, Radhika Srinivasan, Gabriela Bourne, Susan M. Chang, Soonmee Cha, Sarah Nelson, Shelly Gunn, Xavier T. Reveles, Budi Tirtorahardjo, Michelle N. Strecker, Lisa Fichtel. -OMICS AND PROGNOSTIC MARKERS, Neuro-Oncology, 2011, pp. iii76-iii84, 13/suppl 3, DOI: 10.1093/neuonc/nor167