Journal of Shandong University (Health Sciences) ›› 2021, Vol. 59 ›› Issue (11): 19-28.doi: 10.6040/j.issn.1671-7554.0.2021.0603

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Construction of a stemness-based scoring model predicting the efficacy of immunotherapy in lung adenocarcinoma based on public databases

PANG Zhaofei1,2*, LIU Yong1*, ZHAO Xiaogang3, YAN Tao1, CHEN Xiaowei1, DU Jiajun1,4   

  1. 1. Institute of Oncology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong, China;
    2. Department of Oncology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong, China;
    3. Department of Thoracic Surgery, The Second Hospital of Shandong University, Jinan 250033, Shandong, China;
    4. Department of Thoracic Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong, China
  • Published:2021-11-11

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Abstract: Objective To predict immune checkpoint blockade(ICB)response in lung adenocarcinoma(LUAD)by identifying LUAD subtypes related to cancer stem cells and constructing a stemness-based scoring model. Methods LUAD RNA-seq data were obtained from TCGA database. By “limma” package, 329 differentially expressed genes(DEGs)related to cancer stem cells between LUAD(535 cases)and adjacent tissues(59 cases)were identified to classify LUAD into different subtypes(FDR<0.05, |log2 Fold Change|>2). By univariate Cox regression analysis, the common prognostic DEGs among different subtypes were further screened out. Using principal component analysis(PCA)and the 123 common prognostic DEGs, a stemness-based scoring model was established for 630 LUAD patients from TCGA and GEO. The cutoff value, determined by Kaplan-Meier curves analysis, was used to stratify LUAD patients into high- and low-score groups(cutoff value=-1.91). Furthermore, difference of distinct subtypes and stemness-based scores on tumor microenvironment(TME)and ICB therapy were analyzed. Results Thirty-six differentially expressed genes and three LUAD subtypes related to cancer stem cells(CSC-A, CSC-B, and CSC-C)were identified, overall survival rates of which were statistically different(P=0.033). The three subtypes greatly affected immune infiltration levels and were associated with multiple immune pathways, such as antigen presentation and cytotoxicity. A total of 123 common prognostic genes(P<0.05)were screened out to construct stemness-based scoring model by univariate Cox regression. In the low-score group, the infiltration of various immune cells and mRNA expressions of PD1, PD-L1 and CTLA4 were up-regulated. No matter anti-CTLA4 or anti-PD1 treatment alone, or combination of them, efficacy of the low-score group was better than that of the high-score group, and there was no significant difference in the efficacy of the two groups without ICB(P=0.060). In the anti-PD-L1 and anti-PD1 immunotherapy cohorts, the response rates of the low-score group were higher than that of the high-score group(the response rate of the anti-PD-L1 treatment cohorts: 50% vs 20%; the response rate of anti-PD1 treatment cohorts: 23% vs 0%). Conclusion Stemness-based scoring model has a potential to predict the efficacy of ICB therapy in LUAD patients, which is expected to provide a theoretical basis for ICB therapy in LUAD patients.

Key words: Cancer stemness, Immunotherapy, Lung adenocarcinoma, Tumor microenvironment, Immune checkpoint

CLC Number: 

  • R734.2
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