Research Papers:

Cell cycle progression score is a marker for five-year lung cancer-specific mortality risk in patients with resected stage I lung adenocarcinoma

Takashi Eguchi _, Kyuichi Kadota, Jamie Chaft, Brent Evans, John Kidd, Kay See Tan, Joe Dycoco, Kathryn Kolquist, Thaylon Davis, Stephanie A. Hamilton, Kraig Yager, Joshua T. Jones, William D. Travis, David R. Jones, Anne-Renee Hartman and Prasad S. Adusumilli

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Oncotarget. 2016; 7:35241-35256. https://doi.org/10.18632/oncotarget.9129

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Takashi Eguchi1,2, Kyuichi Kadota3,4, Jamie Chaft5, Brent Evans6, John Kidd6, Kay See Tan7, Joe Dycoco1, Kathryn Kolquist6, Thaylon Davis6, Stephanie A. Hamilton6, Kraig Yager6, Joshua T. Jones6, William D. Travis3, David R. Jones1, Anne-Renee Hartman6, Prasad S. Adusumilli1,8

1Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA

2Division of Thoracic Surgery, Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan

3Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

4Department of Diagnostic Pathology, Faculty of Medicine, Kagawa University, Kagawa, Japan

5Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA

6Myriad Genetic Laboratories, Inc., Salt Lake City, UT, USA

7Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA

8Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Correspondence to:

Prasad S. Adusumilli, email: [email protected]

Keywords: molecular prognostic score, CCP score, chemotherapy, adjuvant therapy, overall survival

Received: February 08, 2016    Accepted: April 16, 2016    Published: May 2, 2016


Purpose: The goals of our study were (a) to validate a molecular expression signature (cell cycle progression [CCP] score and molecular prognostic score [mPS; combination of CCP and pathological stage {IA or IB}]) that identifies stage I lung adenocarcinoma (ADC) patients with a higher risk of cancer-specific death following curative-intent surgical resection, and (b) to determine whether mPS stratifies prognosis within stage I lung ADC histological subtypes.

Methods: Formalin-fixed, paraffin-embedded stage I lung ADC tumor samples from 1200 patients were analyzed for 31 proliferation genes by quantitative RT-PCR. Prognostic discrimination of CCP score and mPS was assessed by Cox proportional hazards regression, using 5-year lung cancer–specific mortality as the primary outcome.

Results: In multivariable analysis, CCP score was a prognostic marker for 5-year lung cancer–specific mortality (HR=1.6 per interquartile range; 95% CI, 1.14–2.24; P=0.006). In a multivariable model that included mPS instead of CCP, mPS was a significant prognostic marker for 5-year lung cancer–specific mortality (HR=1.77; 95% CI, 1.18–2.66; P=0.006). Five-year lung cancer–specific survival differed between low-risk and high-risk mPS groups (96% vs 81%; P<0.001). In patients with intermediate-grade lung ADC of acinar and papillary subtypes, high mPS was associated with worse 5-year lung cancer–specific survival (P<0.001 and 0.015, respectively), compared with low mPS.

Conclusion: This study validates CCP score and mPS as independent prognostic markers for lung cancer–specific mortality and provides quantitative risk assessment, independent of known high-risk features, for stage I lung ADC patients treated with surgery alone.

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