Abstract 304P
Background
To identify clinical prognostic factors and explore molecular mechanisms in small cell lung cancer patients with liver metastasis (SCLC-LM), known for poor prognosis due to rapid recurrence and progression.
Methods
A retrospective analysis was conducted on 702 SCLC patients (January 2010–March 2019) and 133 extensive SCLC patients receiving first-line immunotherapy with chemotherapy (January 2020–December 2022). TCGA and GEO datasets were utilized, and immunofluorescence was applied.
Results
Patients with SCLC-LM had the shortest OS compared to those with other or no metastases. Liver metastasis (LM) reduced the objective response rate (ORR) of immunotherapy and negatively impacted progression-free survival (PFS) and OS in extensive SCLC patients on first-line immunotherapy. Cox regression analysis identified diabetes, eosinophils, neutrophils, and albumin as significant independent factors for OS in the SCLC-LM group. BRCA2 and XRCC2 were identified as key upregulated genes linked to SCLC, metastasis, liver metastasis, glucose metabolism, and immunotherapy. These genes were more expressed in SCLC tissues than in adjacent tissues, with a positive correlation between them. The high-BRCA2 group showed higher immune and stromal scores, while the high-XRCC2 group had increased eosinophil infiltration in SCLC. BRCA2 and XRCC2 are crucial in the immune microenvironment, showing high expression and prognostic significance in various cancers, and they negatively impact immune checkpoint blockade response.
Conclusions
Our study indicates that LMdiminishes survival outcomes and the efficacy of immunotherapy in SCLC patients. Furthermore, XRCC2 and BRCA2 are implicated in liver metastasis and the modulation of the immune microenvironment, but further research is needed.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.