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Authors
Parker, Rebecca E.
McSwain, Leon
Zhou, Wei
Marcus, Adam I.
Fu, Haian
Ramalingam, Suresh S.
Zhang, Shirley
Gilbert-Ross, Melissa https://orcid.org/0000-0002-1960-8302
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Funding
Funding for this research was provided by:
National Cancer Institute (R01CA194027, R01CA194027, R01CA194027, P50CA217691, P30CA138292, R01CA194027)
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Article History
Received: 23 May 2025
Accepted: 9 July 2025
First Online: 26 July 2025
Declarations
:
: The authors declare no competing interests.
: Clinical data support the negative prognostic impact of STK11 mutations in metastatic non-small cell lung cancer but using STK11 genomic status to guide treatment response has not gained widespread use. We show that knockdown and genetic deletion of LKB1/STK11 in lung cells are sufficient to upregulate expression levels of PERIOD 1 (PER1) mRNA and protein, and that knockdown of PER1 in LKB1-mutant cell models decreases tumor growth, proliferation, and invasion. In addition, high levels of PER1 in lung adenocarcinoma patients are associated with mutations in STK11, a decrease in CD274 (PD-L1), and lower hypoxia and tumor/stromal ESTIMATE scores—whereas low PER1 levels are associated with TP53 mutations in the TCGA cohort. Our results uncover PER1 as a potential subtype-specific biomarker for response to immunotherapy. Ultimately this could replace the need to use TP53 and STK11 genomic status to guide treatment decisions.
