Lumican is a potential predictor on the efficacy of concurrent chemoradiotherapy in cervical squamous cell carcinoma

Ge Hu; Ying Xiao; Chanchan Ma; Jinyun Wang; Xiaotao Qian; Xiaowei Wu; Fengqin Zhu; Shiying Sun; Junchao Qian

doi:10.1016/j.heliyon.2023.e18011

Lumican is a potential predictor on the efficacy of concurrent chemoradiotherapy in cervical squamous cell carcinoma

Heliyon. 2023 Jul 8;9(7):e18011. doi: 10.1016/j.heliyon.2023.e18011. eCollection 2023 Jul.

Authors

Ge Hu¹, Ying Xiao², Chanchan Ma³, Jinyun Wang¹, Xiaotao Qian¹, Xiaowei Wu¹, Fengqin Zhu¹, Shiying Sun³, Junchao Qian¹

Affiliations

¹ Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei,230031, PR China.
² The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing 211100, PR China.
³ Department of Obstetrics and Gynecology, Second Affiliated Hospital of Anhui Medical University, Hefei, 230031, PR China.

Abstract

Purpose: To identify new novel biomarkers for predicting the efficacy of concurrent chemoradiotherapy(CCRT) in cervical squamous cell carcinoma(CESC).

Methods: Gene expression datasets GSE56363, GSE5787, and GSE168009 were analyzed to identify candidate genes to predict the efficacy of CCRT in CESC. Single-cell RNA sequencing (scRNA-seq) data from GSE168652 and CESC patients in The Cancer Genome Atlas(TCGA) were systematically analyzed to explore possible molecular mechanisms. Kaplan-Meier evaluated the correlation between LUM (Lumican) and prognostic significance. The expression of LUM protein in biopsy tissues before CCRT was detected by immunohistochemistry in 15 CESC patients.

Results: LUM mRNA levels were significantly upregulated in nonresponders of CESC.patients receiving CCRT and positively correlated with poor therapeutic effect. Furthermore, high expression of LUM influenced the immune microenvironment in CESC patient-derived organoids treated with CCRT. LUM overexpression in CESC cells induced resistance to CCRT, potentially via immune landscape modulation. Gene Set Enrichment Analysis (GSEA) revealed that possible mechanisms underlying resistance to CCRT might involve the PARs and IL1 signaling pathway affecting the immune landscape.

Conclusions: High LUM expression is correlated with poor efficacy in CESC patients receiving CCRT, possibly through the PARs and IL1 signaling pathway affecting the immune landscape.

Keywords: Biomarker; CCRT; CESC; LUM.