Prognostic Ferroptosis-Related lncRNA Signatures Associated With Immunotherapy and Chemotherapy Responses in Patients With Stomach Cancer

Donglin Lai; Lin Tan; Xiaojia Zuo; DingSheng Liu; Deyi Jiao; Guoqing Wan; Changlian Lu; Dongjie Shen; Xuefeng Gu

doi:10.3389/fgene.2021.798612

Prognostic Ferroptosis-Related lncRNA Signatures Associated With Immunotherapy and Chemotherapy Responses in Patients With Stomach Cancer

Front Genet. 2022 Jan 3:12:798612. doi: 10.3389/fgene.2021.798612. eCollection 2021.

Authors

Donglin Lai^{1

2}, Lin Tan³, Xiaojia Zuo¹, DingSheng Liu¹, Deyi Jiao⁴, Guoqing Wan¹, Changlian Lu¹, Dongjie Shen⁵, Xuefeng Gu^{1

2

4}

Affiliations

¹ Shanghai Key Laboratory of Molecular Imaging, Zhoupu Hospital, Shanghai University of Medicine and Health Sciences, Shanghai, China.
² School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, China.
³ The Affiliated Zhuzhou Hospital Xiangya Medical College CSU, Zhuzhou, China.
⁴ School of Pharmacy, Shanghai University of Medicine and Health Sciences, Shanghai, China.
⁵ Department of General Surgery, Ruijin Hospital Luwan Branch, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Abstract

Ferroptosis is associated with the prognosis and therapeutic responses of patients with various cancers. LncRNAs are reported to exhibit antitumor or oncogenic functions. Currently, few studies have assessed the combined effects of ferroptosis and lncRNAs on the prognosis and therapy of stomach cancer. In this study, transcriptomic and clinical data were downloaded from TCGA database, and ferroptosis-related genes were obtained from the FerrDb database. Through correlation analysis, Cox analysis, and the Lasso algorithm, 10 prognostic ferroptosis-related lncRNAs (AC009299.2, AC012020.1, AC092723.2, AC093642.1, AC243829.4, AL121748.1, FLNB-AS1, LINC01614, LINC02485, LINC02728) were screened to construct a prognostic model, which was verified in two test cohorts. Risk scores for patients with stomach cancer were calculated, and patients were divided into two risk groups. The low-risk group, based on the median value, had a longer overall survival time in the KM curve, and a lower proportion of dead patients in the survival distribution curve. Potential mechanisms and possible functions were revealed using GSEA and the ceRNA network. By integrating clinical information, the association between lncRNAs and clinical features was analyzed and several features affecting prognosis were identified. Then, a nomogram was developed to predict survival rates, and its good predictive performance was indicated by a relatively high C-index (0.67118161) and a good match in calibration curves. Next, the association between these lncRNAs and therapy was explored. Patients in the low-risk group had an immune-activating environment, higher immune scores, higher TMB, lower TIDE scores, and higher expression of immune checkpoints, suggesting they might receive a greater benefit from immune checkpoint inhibitor therapy. In addition, a significant difference in the sensitivity to mitomycin. C, cisplatin, and docetaxel, but not etoposide and paclitaxel, was observed. In summary, this model had guiding significance for prognosis and personalized therapy. It helped screen patients with stomach cancer who might benefit from immunotherapy and guided the selection of personalized chemotherapeutic drugs.

Keywords: chemotherapy; ferroptosis; immunotherapy; lncRNA; prognostic; stomach cancer.