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Thorax. 2019 Apr;74(4):371-379. doi: 10.1136/thoraxjnl-2018-212194. Epub 2018 Nov 24.

5 protein-based signature for resectable lung squamous cell carcinoma improves the prognostic performance of the TNM staging.

Author information

Program in Solid Tumors, CIMA, Pamplona, Spain.
Department of Pathology, Anatomy and Physiology, School of Medicine, University of Navarra, Pamplona, Spain.
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Navarra Health Research Institute (IDISNA), Pamplona, Spain.
Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.
Neumology Service, Parc Taulí Universitary Hospital, Sabadell, Spain.
CIBER de Enfermedades Respiratorias-CIBERES, Instituto de Salud Carlos III, Madrid, Spain.
Vall d'Hebron University Hospital, Institute of Oncology, Barcelona, Spain.
Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain.
Department of Thoracic Surgery, Clínica Universidad de Navarra, Pamplona, Spain.
Department of Oncology, Clínica Universidad de Navarra, Pamplona, Spain.
Department of Pathology, Clínica Universidad de Navarra, Pamplona, Spain.
Department of Neumology, Clínica Universidad de Navarra, Pamplona, Spain.
Department of Biochemistry and Genetics, School of Sciences, University of Navarra, Pamplona, Spain.
Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.



Prognostic biomarkers have been very elusive in the lung squamous cell carcinoma (SCC) and none is currently being used in the clinical setting. We aimed to identify and validate the clinical utility of a protein-based prognostic signature to stratify patients with early lung SCC according to their risk of recurrence or death.


Patients were staged following the new International Association for the Study of Lung Cancer (IASLC) staging criteria (eighth edition, 2018). Three independent retrospective cohorts of 117, 96 and 105 patients with lung SCC were analysed to develop and validate a prognostic signature based on immunohistochemistry for five proteins.


We identified a five protein-based signature whose prognostic index (PI) was an independent and significant predictor of disease-free survival (DFS) (p<0.001; HR=4.06, 95% CI 2.18 to 7.56) and overall survival (OS) (p=0.004; HR=2.38, 95% CI 1.32 to 4.31). The prognostic capability of PI was confirmed in an external multi-institutional cohort for DFS (p=0.042; HR=2.01, 95% CI 1.03 to 3.94) and for OS (p=0.031; HR=2.29, 95% CI 1.08 to 4.86). Moreover, PI added complementary information to the newly established IASLC TNM 8th edition staging system. A combined prognostic model including both molecular and anatomical (TNM) criteria improved the risk stratification in both cohorts (p<0.05).


We have identified and validated a clinically feasible protein-based prognostic model that complements the updated TNM system allowing more accurate risk stratification. This signature may be used as an advantageous tool to improve the clinical management of the patients, allowing the reduction of lung SCC mortality through a more accurate knowledge of the patient's potential outcome.


clinical utility; disease-free survival; immunohistochemistry; overall survival; prognosis; signature; squamous cell carcinoma

Conflict of interest statement

Competing interests: JA, EMT, MJP, RP and LMM are listed as co-inventors of a recently applied patent related to some of the results included in this manuscript.

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