Comprehensive analysis of a real-world cohort identifies geranylgeranyl diphosphate synthase 1 as a predictor of chemoresistance in small cell lung cancer.
Yi Deng, Chenchen Guo, Tengfei Zhang, Yuan Chen, Xin Zhang, Hongbin Ji, Liang Hu
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引用次数: 0
Abstract
A subset of patients with small cell lung cancer (SCLC) exhibit intrinsic resistance to chemotherapy. However, biomarkers that effectively predict this group of patients are still lacking. We previously reported that high geranylgeranyl diphosphate synthase 1 (GGPS1) expression is associated with poor overall survival (OS) in SCLC, and statin combination therapy is effective in overcoming chemoresistance, especially in GGPP-high SCLC. However, the expression patterns of GGPS1 in SCLC subtypes and its relationship with clinical chemotherapy response remain unclear, and whether GGPS1 indicates statin treatment sensitivity in chemoresistant SCLC needs further validation. Through integrative analyses of 146 real-world SCLC cases, we found that approximately 25% exhibited high GGPS1 expression. Subgroup analysis revealed that GGPS1 expression was higher in the ASCL1/NEUROD1/POU2F3 triple-negative subgroup. Moreover, high GGPS1 expression was significantly correlated with reduced objective response rate (ORR) and progression-free survival (PFS) as well as OS. In addition, analysis of seven paired biopsy samples demonstrated that GGPS1 was upregulated in chemoresistant SCLC. We further showed that the combination of etoposide and cisplatin (E/P) with statins had improved efficacy in a patient-derived xenograft (PDX) model derived from a relapsed patient with high GGPS1 expression. Our findings suggest that GGPS1 is a promising biomarker for predicting chemoresistance in SCLC and may be a potential indicator of sensitivity to statin combination therapy in chemoresistant SCLC.
期刊介绍:
The International Journal of Cancer (IJC) is the official journal of the Union for International Cancer Control—UICC; it appears twice a month. IJC invites submission of manuscripts under a broad scope of topics relevant to experimental and clinical cancer research and publishes original Research Articles and Short Reports under the following categories:
-Cancer Epidemiology-
Cancer Genetics and Epigenetics-
Infectious Causes of Cancer-
Innovative Tools and Methods-
Molecular Cancer Biology-
Tumor Immunology and Microenvironment-
Tumor Markers and Signatures-
Cancer Therapy and Prevention