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CILP is a potential pan-cancer marker: combined silico study and in vitro analyses

Abstract

CILP (Cartilage intermediate layer protein), an ECM (extracellular matrix) glycoprotein, is found to be associated with intervertebral disc degeneration, chronic heart failure, obese and cardiac fibrosis. However, there are few reports on the role of CILP in tumors. Thus, in this study, we mainly explored the function of CILP in the occurrence and development of tumors and whether it could be a potential pan-cancer marker. Pan-cancer data in this study were obtained from UCSC Xena. Single-cell data were obtained from GSE152938. ROC (Receiver operating characteristic) curves were used to evaluate the accuracy of CILP in predicting the occurrence of different tumor types. The Kaplan–Meier plots were used to assess the relationship between CILP expression and survival prognosis in different tumor types by COX regression analysis. Pseudotime analysis and cell communication analysis were used to further explore the function of CILP at Single cell level. The human RCC (renal cell carcinoma) cell lines ACHN and 786-O were used for further experimental verification. Bulk RNA-seq showed differences in CILP expression in several tumors. ROC curves showed that 14 tumors have AUC > 0.7. Kaplan–Meier plots indicated that CILP is a risk factor for patients in 3 kinds of tumors. ScRNA-seq (Single cell RNA sequencing) suggested that CILP might influence tumors through fibroblasts and cell–cell communication. Finally, we verified the function of CILP at the cellular level by using RCC cell lines ACHN and 786-O and found that knockdown of CILP could significantly inhibit migration and invasion. This finding supports that CILP could be a risk factor as well as a pan-cancer predictor for patients.

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Fig. 1: Expression profiles of CILP in different tumors.
Fig. 2: ROC curve for CILP in different tumors.
Fig. 3: Correlations between CILP expression and the prognosis overall survival in different tumors.
Fig. 4: Associations between CILP expression and T stage in different tumors.
Fig. 5: Single-cell RNA sequencing of KIRC in GSE152938.
Fig. 6: Pseudotime analysis of CILP in fibroblasts of KIRC.
Fig. 7: Analysis of CILP in cell–cell communication of KIRC.
Fig. 8: CILP knockdown inhibited migration and invasion in RCC cell lines.
Fig. 9: GO/KEGG and GSEA analysis in KIRC.

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Data availability

The datasets used and analyzed during the present study are available from the corresponding author on reasonable request.

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Funding

This study was supported by grants from the National Natural Science Foundation of China (81803541) and Shanghai Science and Technology Development Foundation (22140901900).

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SZ designed the study. BG and FZ performed data analysis. SZ wrote the manuscript and helped validate data authenticity. BG reviewed and revised the manuscript. All authors contributed to the paper and agreed to submit the final manuscript.

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Correspondence to Sailong Zhang.

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Guo, B., Zhao, F. & Zhang, S. CILP is a potential pan-cancer marker: combined silico study and in vitro analyses. Cancer Gene Ther 31, 119–130 (2024). https://doi.org/10.1038/s41417-023-00688-x

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