Abstract 221P
Background
Recurrent Malignant pleural effusion (MPE) resulting from non-small-cell lung cancer (NSCLC) is easily refractory to conventional therapeutics and lacks predictive or diagnostic markers. The cellular or genetic signatures of recurrent MPE still remain largely uncertain.
Methods
Sixteen patients with pleural effusions were recruited, followed by corresponding treatments based on primary tumors. Non-recurrent or recurrent MPE was determined after three to six weeks of treatments. The status of MPE was verified by computer tomography and cytopathology, and the baseline pleural fluids were collected for scRNA-seq. Samples were integrated and profiled. Cellular communications and trajectories were inferred by bioinformatic algorithms. Comparative analysis was conducted and the results were further validated by quantitative polymerase chain reaction in a larger MPE cohort (N=64).
Results
Cancer cell cluster C1 was significantly enriched in the recurrent MPE group. Conserved markers profiling indicated cancer cell clusters C1, C5, C8, and C12 were heterogeneous though remaining uniform signatures. Nevertheless, the C1 cluster classified as EpCAM+ metastatic cancer cell demonstrated distinct signaling correlated with activation of tight junction and adherence junction, in which Claudin-4 (CLDN4) was identified. The subset cluster C3 of total C1 cluster favoring recurrent MPE showed a significantly higher expression of CLDN4, indicating a phenotype of ameboidal-type cell migration. Its expression was positively correlated with ELF3, EpCAM and TACSTD2, independent of driver-gene status. CLDN4 was also found to be correlated with HIF1A and VEGFA expression, and cancer cell cluster C1 was the major mediator in cellular communication of VEGFA signaling. In our extensive MPE cohort, we found a significantly increased expression of CLDN4 in pleural effusion cells among patients with recurrent MPE compared with the non-recurrent group, which was also associated with a trend towards worse overall survival.
Conclusions
Our results indicated that CLDN4 was a predictive marker of recurrent MPE among patients with advanced NSCLC with clinical application value.
Legal entity responsible for the study
The authors.
Funding
Shanghai Key clinical specialty construction project - Respiratory Medicine (201912-0552).
Disclosure
All authors have declared no conflicts of interest.