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ORIGINAL RESEARCH article
Front. Oncol.
Sec. Cancer Immunity and Immunotherapy
Volume 14 - 2024 |
doi: 10.3389/fonc.2024.1448966
Exploring the Impact of HDL and LMNA Gene Expression on Immunotherapy Outcomes in NSCLC: A Comprehensive Analysis Using Clinical & Gene data
Provisionally accepted- Beijing Friendship Hospital, Capital Medical University, Beijing, China
Objectives: Analyzing the impact of peripheral lipid levels on the efficacy of immune checkpoint inhibitor therapy in non-small cell lung cancer (NSCLC) patient populations and exploring whether it can serve as a biomarker for broadening precise selection of individuals benefiting from immunotherapy.We retrospectively collected clinical data from 201 cases of NSCLC patients receiving immune checkpoint inhibitor therapy. The clinical information included biochemical indicators like total cholesterol, triglycerides, high-density lipoprotein (HDL), and low-density lipoprotein (LDL). We utilized machine learning algorithms and Cox proportional hazards regression models to investigate independent predictors for both short-term and long-term efficacy of immunotherapy. Additionally, we concurrently developed a survival prediction model. Analyzing the Genes of Patients with Treatment Differences to Uncover Mechanisms Results: Correlation analysis revealed a significant positive association between HDL and ORR, DCR, and PFS. T-test results indicated that the high-HDL group exhibited higher DCR (81.97% vs. 45.57%) and ORR (61.48% vs. 16.46%). Kruskal-Wallis test showed that the high-HDL group had a longer median PFS (11 months vs. 6 months). Utilizing six machine learning algorithms, we constructed models to predict disease relief and stability. The model built using the random forest algorithm demonstrated superior performance, with AUC values of 0.858 and 0.802. Furthermore, both univariate and multivariate Cox analyses identified HDL and LDL as independent risk factors for predicting PFS. In patients with poor immunotherapy response, there is upregulation of BCL2L11, AKT1, and LMNA expression.Conclusions: HDL and LDL are independent factors influencing the survival prognosis of NSCLC patients undergoing immune checkpoint inhibitor therapy. HDL is expected to become new biomarkers for predicting the immunotherapy efficacy in patients with NSCLC.In patients with poor immunotherapy response, upregulation of the LMNA gene leads to apoptosis resistance and abnormal lipid metabolism.
Keywords: Non-small cell lung cancer, immune checkpoint inhibitor therapy, high-density lipoprotein, enrich analysis, machine learning, LMNA
Received: 14 Jun 2024; Accepted: 02 Sep 2024.
Copyright: © 2024 Li, Wang and Cao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Bangwei Cao, Beijing Friendship Hospital, Capital Medical University, Beijing, China
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