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. 2022 Dec 26;30(1):333-343.
doi: 10.3390/curroncol30010027.

LKB1 Loss Assessed by Immunohistochemistry as a Prognostic Marker to First-Line Therapy in Advanced Non-Small-Cell Lung Cancer

Alejandro Avilés-Salas  1 , Diego A Díaz-García  1   2 , Luis Lara-Mejía  1 , Andrés F Cardona  3 , Mario Orozco-Morales  2   4 , Rodrigo Catalán  1   2 , Norma Y Hernández-Pedro  1   2 , Eduardo Rios-Garcia  1   2 , Maritza Ramos-Ramírez  1   2 , Oscar Arrieta  1   2
Affiliations

LKB1 Loss Assessed by Immunohistochemistry as a Prognostic Marker to First-Line Therapy in Advanced Non-Small-Cell Lung Cancer

Alejandro Avilés-Salas et al. Curr Oncol. .

Abstract

(1) Background: Liver kinase B1 (LKB1) is a tumor suppressor gene involved in cell growth and metabolism. However, its alterations are not routinely assessed for guiding therapy in clinical practice. We assessed LKB1 expression by immunohistochemistry as a potential biomarker. (2) Methods: This bicentric retrospective cohort study analyzed data from patients with advanced NSCLC who initiated platinum-based chemotherapy or epidermal growth factor receptor- tyrosine kinase inhibitor (EGFR-TKI) between January 2016 and December 2020. Kaplan-Meier and Cox regression models were used for survival curves and multivariate analysis. (3) Results: 110 patients were evaluated, and the clinical stage IV predominated the lung adenocarcinoma histology. LKB1 loss was observed in 66.3% of cases. LKB1 loss was associated with non-smokers, the absence of wood smoke exposure and an EGFR wild-type status. The median progression-free survival (PFS) and overall survival (OS) in the population were 11.1 and 26.8 months, respectively, in the loss group, compared with cases exhibiting a positive expression. After an adjustment by age, smoking status, Eastern Cooperative Oncology Group Performance Score (ECOG-PS), EGFR status and type of administered therapy, LKB1 loss was significantly associated with worse PFS and OS. (4) Conclusion: Patients with an LKB1 loss had worse clinical outcomes. This study warrants prospective assessments to confirm the prognostic role of the LKB1 expression in advanced NSCLC.

Keywords: STK11; advanced NSCLC; immunohistochemistry; lung cancer; prognostic biomarker.

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Conflict of interest statement

Oscar Arrieta has received honours as an advisor, participated in the speakers’ bureau, and given expert opinions to Pfizer, AstraZeneca, Boehringer-Ingelheim, Roche, Lilly, and Bristol-Myers Squibb. Andrés F. Cardona reports grants from Merck Sharp & Dohme, grants from Boehringer Ingelheim, grants from Roche, grants from Bristol-Myers Squibb, grants from The Foundation for Clinical and Applied Cancer Research-FICMAC, personal fees from Merck Sharp & Dohme, personal fees from Boehringer Ingelheim, personal fees from Roche, personal fees from Bristol-Myers Squibb, personal fees from Pfizer, personal fees from Novartis, personal fees from Celldex Therapeutics, personal fees from Foundation Medicine, personal fees from Eli Lilly, personal fees from Foundation for Clinical and Applied Cancer Research-FICMAC, outside the submitted work; and Other from Pfizer, Boehringer Ingelheim, Astra Zeneca, MSD, BMS, Celldex, Roche. Luis Lara-Mejía has participated in the speakers’ bureau of Roche, Pfizer and Boehringer Ingelheim. The other authors declare no potential conflict of interest.

Figures

Figure 1
Figure 1
LKB1 expression assessment in lung tissue from samples of patients with lung adenocarcinoma (×100). (a) Negative LKB1 expression. (b) Positive LKB1 expression.
Figure 2
Figure 2
(a) Progression free survival and (b) Overall survival in the total population.
Figure 3
Figure 3
(a) Progression free survival based on LKB1 expression and (c) after adjustment for EGFR status. (b) Overall survival according to LKB1 expression and (d) after adjustment for EGFR status.
See this image and copyright information in PMC

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