Faculty Collaboration Database

Transcriptomics in Tumor and Normal Lung Tissues Identify Patients With Early-Stage Non-Small-Cell Lung Cancer With High Risk of Postsurgery Recurrence Who May Benefit From Adjuvant Therapies. JCO Precis Oncol 2022 Sep;6:e2200072

Date

09/16/2022

Pubmed ID

36108261

Pubmed Central ID

PMC9489166

DOI

10.1200/PO.22.00072

Abstract

PURPOSE: The prognosis of patients with non-small-cell lung cancer (NSCLC), traditionally determined by anatomic histology and TNM staging, neglects the biological features of the tumor that may be important in determining patient outcome and guiding therapeutic interventions. Identifying patients with NSCLC at increased risk of recurrence after curative-intent surgery remains an important unmet need so that known effective adjuvant treatments can be offered to those at highest risk of recurrence.

METHODS: Relative gene expression level in the primary tumor and normal bronchial tissues was used to retrospectively assess their association with disease-free survival (DFS) in a cohort of 120 patients with NSCLC who underwent curative-intent surgery.

RESULTS: Low versus high Digital Display Precision Predictor (DDPP) score (a measure of relative gene expression) was significantly associated with shorter DFS (highest recurrence risk; P = .006) in all patients and in patients with TNM stages 1-2 (P = .00051; n = 83). For patients with stages 1-2 and low DDPP score (n = 29), adjuvant chemotherapy was associated with improved DFS (P = .0041). High co-overexpression of CTLA-4, PD-L1, and ICOS in normal lung (28 of 120 patients) was also significantly associated with decreased DFS (P = .0013), suggesting an immune tolerance to tumor neoantigens in some patients. Patients with DDPP low and immunotolerant normal tissue had the shortest DFS (P = 2.12E-11).

CONCLUSION: TNM stage, DDPP score, and immune competence status of normal lung are independent prognostic factors in multivariate analysis. Our findings open new avenues for prospective prognostic assessment and treatment assignment on the basis of transcriptomic profiling of tumor and normal lung tissue in patients with NSCLC.

Author List

Lazar V, Girard N, Raymond E, Martini JF, Galbraith S, Raynaud J, Bresson C, Solomon B, Magidi S, Nechushtan H, Onn A, Berger R, Chen H, Al-Omari A, Ikeda S, Lassen U, Sekacheva M, Felip E, Tabernero J, Batist G, Spatz A, Pramesh CS, Girard P, Blay JY, Philip T, Berindan-Neagoe I, Porgador A, Rubin E, Kurzrock R, Schilsky RL

Author

Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

B7-H1 Antigen
CTLA-4 Antigen
Carcinoma, Non-Small-Cell Lung
Humans
Lung
Lung Neoplasms
Prospective Studies
Retrospective Studies
Small Cell Lung Carcinoma
Transcriptome