e20561 Background: It has been shown that PDLIM2 is expressed at higher levels in normal lungs in comparison to cancerous lungs, where it modulates transcription factors as a tumor suppressor. PDLIM2 upregulates T-cell activation and antigen presentation but also downregulates resistance genes in malignant cells. Prior studies link expanded distant metastases and lung adenocarcinoma size to patients with simultaneous KRAS mutations, TP53 deletions, and decreased PDLIM2. This study investigates PDLIM2 expression amongst various patient populations, cancer characteristics, and disease trajectories. Methods: The study was IRB approved. From an initial 226 patient samples that underwent next generation sequencing, 196 samples were primary lung cancers. Patient charts were reviewed for KRAS, STK11, TP53, and NFE2L2 pathologic variants. Of the KRAS positive patients, 27 folders of RNA samples were analyzed for PDLIM2 expression using Salmon software. In total, 21 patients were analyzed, though exclusions were made for patients who did not meet specific categorical designations. We generated normalized ratios (NR) for PDLIM2 expression, collected patient demographic and clinical data and utilized T-tests and Kaplan-Meier curves for statistical analyses. Results: Despite the cohort size limiting statistical significance, meaningful trends emerged. 73% of ever smokers (n = 11/15) completely suppressed PDLIM2 compared to the 33% of never smokers (n = 2/6, p = 0.539). PDLIM2 expression was seen to decrease five-fold as tumor burden increased, with average NR of 0.026 in T1-T2 stage patients versus 0.005 in T3-T4 (p = 0.190). The decrease in metastasis was six-fold with an average NR of 0.035 in M0 patients compared to 0.006 in M1 patients (p = 0.345). TP53 mutated cancers displayed lower expression than those without (0.005 vs 0.022, p = 0.216). The only patient with an NFE2L2 mutation had a NR of 0. STK pathologic variants had an average NR 0.043 compared to 0.010 in patients without (p = 0.501). No statistically significant differences were observed in PDLIM2 expression according to patient age (p = 0.545), race (p = 0.735), or tumor location (p = 0.734). Kaplan-Meier curves for progression-free survival (PFS) did not exhibit a significant difference (p = 0.769). Overall survival (OS) data was not formally analyzed due to limited mortality events (n = 2). Conclusions: Overall, PDLIM2 expression may be a marker of aggressive tumor biology given its likely relation to tumor invasion, metastasis, KRAS and TP53 status, independent of patient demographics. There is also a strong likelihood of relation to tobacco exposure. Lastly, the association between NFE2L2 status and PDLIM2 expression raises the possibility that PDLIM2 is a mechanism by which patients with NFE2L2 mutations are insensitive to immune checkpoint inhibition. This study is limited by small sample size, indicating the need for larger studies to further investigate these patterns.
Sur et al. (Thu,) studied this question.