Development and validation of an autophagy-related long non-coding RNA prognostic signature for cervical squamous cell carcinoma and endocervical adenocarcinoma

Shuguang Zhou; Weiyu Zhang; Wujun Cao; Qinqin Jin; Xiya Jiang; Xiaomin Jiang; Yinting Yang; Hui Yao; Guo Chen; Wei Gao; Yuting Zhu; Jian Qi; Zhuting Tong

doi:10.3389/fonc.2022.1049773

Development and validation of an autophagy-related long non-coding RNA prognostic signature for cervical squamous cell carcinoma and endocervical adenocarcinoma

Front Oncol. 2022 Nov 3:12:1049773. doi: 10.3389/fonc.2022.1049773. eCollection 2022.

Authors

Shuguang Zhou^{1

2}, Weiyu Zhang^{1

2}, Wujun Cao³, Qinqin Jin^{1

2}, Xiya Jiang^{1

2}, Xiaomin Jiang^{1

2}, Yinting Yang^{1

2}, Hui Yao^{1

2}, Guo Chen^{1

2}, Wei Gao^{1

2}, Yuting Zhu^{1

2}, Jian Qi⁴, Zhuting Tong⁵

Affiliations

¹ Department of Gynecology, Anhui Medical University Affiliated Maternity and Child Healthcare Hospital, Hefei, China.
² Department of Gynecology, Anhui Province Maternity and Child Healthcare Hospital, Hefei, China.
³ Department of Clinical Laboratory, Anhui Province Maternity and Child Healthcare Hospital, Hefei, China.
⁴ Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, China.
⁵ Department of Radiation Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Abstract

Background: In this study, we aimed to investigate the signature of the autophagy-related lncRNAs (ARLs) and perform integrated analysis with immune infiltration in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC).

Methods and results: The UCSC Xena and HADb databases provided the corresponding data. The ARLs were selected via constructing a co-expression network of autophagy-related genes (ARGs) and lncRNAs. Univariate Cox regression analysis combined with LASSO regression and multivariate Cox regression analysis were utilized to screen lncRNAs. The ARL risk signature was established by Cox regression and tested if it was an independent element bound up with patient prognosis. We used the xCell algorithm and ssGSEA to clarify the pertinence between immune infiltration and the expression of ARLs. Finally, we predicted the sensitivity of drug treatment as well as the immune response. Results indicated that the three prognostic ARLs (SMURF2P1, MIR9-3HG, and AC005332.4) possessed significant diversity and constituted the ARL signature. Risk score was an individual element (HR = 2.82, 95% CI = 1.87-4.30; p < 0.001). Immune infiltration analysis revealed significant increases in central memory CD8⁺ T cells, endothelial cells, CD8⁺ naive T cells, and preadipocytes in the high-risk group (p < 0.05). There were 10 therapeutic agents that varied significantly in their estimated half-maximal inhibitory concentrations in the two groups. According to the experimental validation, we found that SMURF2P1 belongs to the co-stimulatory genes and might assume greater importance in the development of cervical adenocarcinoma. MIR9-3HG and AC005332.4 belonged to the tumor-suppressor genes and they may play a more positive role in cervical squamous cell carcinoma.

Conclusions: This research explored and validated a novel signature of the ARLs, which can be applied to forecast the prognosis of patients with CESC and is closely associated with immune infiltration.

Keywords: autophagy-related genes (ARGs); autophagy-related lncRNAs (ARLs); cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC); immune infiltration; long noncoding RNA (lncRNA); prognostic signature.