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PLA2G2D and CHIT1: Potential biomarkers for immune infiltration and prognosis in cervical squamous cell carcinoma
doi: 10.1515/fzm-2024-0012
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Abstract:
Objective The aim of this study was to identify biomarkers associated with immunity and prognosis in patients with cervical cancer. Materials and methods Data from patients with cervical squamous cell carcinoma (CESC) were retrieved from the UCSC Xena database and subjected to analysis. Gene sets representing 22 types of immunocytes were acquired, and immunocytes relevant to prognosis were identified. Weighted gene co-expression network analysis (WGCNA) was utilized to identify gene modules associated with prognosis-related immunocytes and to construct immune-related gene markers. Differentially expressed genes were then screened, and the association between immune score and biological function of immune-related gene markers was analyzed. Furthermore, tissue samples from cervical cancer patients in Northeast China were collected to validate the expression of two genes using real-time PCR and immunohistochemistry. Results This study identified 10 immunocytes significantly correlated with overall survival time in patients. Six gene modules were identified as significantly associated with prognosis-related immunocytes, with gene module 6 showing relevance to all prognosis-related immunocytes. Gene module 6 was related to all prognosis-related immunocytes. Moreover, two genes (including PLA2G2D and CHIT1) were found to be significantly associated with overall survival in cancer patients. Patients with CESC were classified into high and low immune score groups based on the median score of gene markers. Correlation analysis of the immune score and biological function was performed. Immunohistochemistry and real-time PCR results revealed high expression of CHIT1 and PLA2G2D in CESC tumor tissues. Conclusion PLA2G2D and CHIT1 show promise as biomarkers for evaluating immune infiltration and prognosis in patients with cervical cancer. -
Key words:
- cervical cancer /
- immune cells /
- overall survival /
- immune score /
- genes
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Figure 2. WGCNA analysis
(A) WGCNA determines optimal threshold; (B) WGCNA hierarchical clustering; (C) Correlation analysis map between gene module and immune cell score.
Figure 3. LASSO regression analysis
(A) The larger the lambda is, the closer the regression coefficient tends to zero; (B) The smaller the likelihood deviation is, the better the model fittingis; (C) Survival curve of immune-related gene marker scores.
Figure 4. Survival association analysis of immune-related gene markers
(A) Multivariate cox proportional risk model analysis; (B) Nomogram of survival prediction of cervical squamous cell carcinoma (CESC) patients; (C) ROC curve analysis.
Figure 5. The overall survival of the gene markers in stage Ⅱ and stage Ⅲ cervical squamous cell carcinoma (CESC) patients
Figure 6. Immune score differences between the high immune-related gene marker score group and the low immune-related gene marker score group
(A) Difference of immune score from ESTIMATE data resource; (B) Difference of immune score from TIDE data resource.
Figure 7. Analysis of biological function differences between the high immune-related gene marker score group and the low immune-related gene marker score group
(A) Biologic process function of differentially expressed genes; (B) Cellular components function of differentially expressed genes; (C) Molecular functions of differentially expressed genes; (D) KEGG pathway enrichment analysis of differentially expressed genes.
Figure 8. The expression of PLA2G2D and CHIT1 between cervical squamous cell carcinoma (CESC) patients and normal samples
Figure 9. Expression changes of PLA2G2D and CHIT1 in tumor tissues of cervical squamous cell carcinoma (CESC) patients and normal controls
(A) Negative expression of PLA2G2D in normal cervical epithelium; (B-C) Low and high expression of PLA2G2D in cervical squamous cell carcinoma; (D-E) Low and high expression of PLA2G2D in cervical adenocarcinoma; (F) Negative expression of CHIT1 in normal cervical epithelium; (G-H) Low and high expression of CHIT1 in cervical squamous cell carcinoma; (I-J) Low and high expression of CHIT1 in cervical adenocarcinoma (100x); (K-L) Immunohistochemical results of expression of PLA2G2D and CHIT1 in tumor tissues of CESC patients and normal controls.
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