Abstract 120P
Background
NSCLC accounts for 80-85% of lung cancer cases, a major global mortality factor. Identifying treatment-responsive biomarkers in NSCLC is crucial for real-time therapeutic evaluation. Tumor-derived exosomes and their mRNAs are recognized for influencing tumor dynamics within the microenvironment. The Hippo and HIF1A pathways are central to cancer progression and are potential therapeutic targets in NSCLC. Despite research advances, the specific treatment-related molecular mechanisms remain incompletely understood. This study aimed to assess Hippo and HIF1A pathway genes in NSCLC exosomal mRNAs pre- and post-treatment.
Methods
In this study, we assessed exosomal mRNAs from plasma pre-and post-treatment in 20 NSCLC patients, of which 6 met curative criteria based on performance status, non-metastatic disease, and absence of EGFR or ALK mutations. Blood samples were collected pre-and post-treatment. Exosomal visualization utilized TEM, and size distributions were confirmed via NTA. Gene expressions pertinent to the Hippo and HIF1A pathways, including YAP, TAZ, LATS1, MST1, HIF1A, MOB1, SIAH2, and VHL, were quantified using qPCR.
Results
The participants, with a mean age of 69 years and classified as stage Ib-IIIa, showed significant exosomal gene expression variations pre- and post-treatment, excluding the VHL gene (p<0.05). When correlated with patient clinicopathological data, metastasis was notably linked with exoSIAH2 (p=0.001) and exoTAZ (p=0.019) expression alterations. Downregulated exoSIAH2 (p=0.018) and elevated exoLATS1 (p=0.050) and exoTAZ (p=0.043) levels indicated tumor progression. A significant relationship was also found between pre-treatment exoMST, exoYAP, and exoHIF1A levels and lymph node metastasis (p=0.045, p=0.017, p=0.018, respectively). Additionally, PD-L1 expression pre-treatment was more pronounced in patients with elevated exoMOB1 levels (>50%) (p=0.001).
Conclusions
Exosomes may modulate tumor progression, with exosomal mRNAs potentially mediating intratumoral cell communication. While broader cohorts require additional clinical verification, these results imply that the Hippo and HIF1A pathways could be pivotal in NSCLC, offering potential therapeutic avenues.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.