A construction and comprehensive analysis of ceRNA networks and infiltrating immune cells in papillary renal cell carcinoma

Abstract

Background As the second most common malignancy in adults, papillary renal cell carcinoma (PRCC) has shown an increasing trend in both incidence and mortality. Effective treatment for advanced metastatic PRCC is still lacking. In this study, we aimed to establish competitive endogenous RNA (ceRNA) networks related to PRCC tumorigenesis, and analyze the specific role of differentially expressed ceRNA components and infiltrating immune cells in tumorigenesis. Methods CeRNA networks were established to identify the key ceRNAs related to PRCC tumorigenesis based on the 318 samples from The Cancer Genome Atlas database (TCGA), including 285 PRCC and 33 normal control samples. The R package, “CIBERSORT,” was used to evaluate the infiltration of 22 types of immune cells. Then we identified the significant ceRNAs and immune cells, based on which two nomograms were obtained for predicting the prognosis in PRCC patients. Finally, we investigated the co‐expression of PRCC‐specific immune cells and core ceRNAs via Pearson correlation test. Results COL1A1, H19, ITPKB, LDLR, TCF4, and WNK3 were identified as hub genes in ceRNA networks. Four prognostic‐related tumor‐infiltrating immune cells, including T cells CD4 memory resting, Macrophages M1, and Macrophages M2 were revealed. Pearson correlation test indicated that Macrophage M1 was negatively related with COL1A1 (p < 0.01) and LDLR (p < 0.01), while Macrophage M2 was positively related with COL1A1 (p < 0.01), TCF4 (p < 0.01), and H19 (p = 0.032). Two nomograms were conducted with favorable accuracies (area under curve of 1‐year survival: 0.935 and 0.877; 3‐year survival: 0.849 and 0.841; and 5‐year survival: 0.818 and 0.775, respectively). Conclusion The study constructed two nomograms suited for PRCC prognosis predicting. Moreover, we concluded that H19‐miR‐29c‐3p‐COL1A1 axis might promote the polarization of M2 macrophages and inhibit M1 macrophage activation through Wnt signaling pathway, collaborating to promote PRCC tumorigenesis and lead to poor overall survival of PRCC patients.

Long Non-Coding RNAs as Novel Biomarkers in the Clinical Management of Papillary Renal Cell Carcinoma Patients: A Promise or a Pledge?

“…The expression of many lncRNAs is altered in pRCC. LncRNAs, together with miR-NAs and mRNAs, form intricate gene expression regulatory networks that play a crucial [134,136,[138][139][140][156][157][158][159]162,164,169,182,183].…”

“…The cellular mechanism of action for CAMK2B relates to inhibiting proliferation and remodeling angiogenesis and fibrogenesis, likely through inhibiting downstream effector genes, including vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)β, and close homolog of L1 (CHL1) [139]. To investigate the regulatory potential of pRCC toward the infiltrating immune cells related to tumorigenesis, the evaluation of the ceRNA network was based on the 318 samples from TCGA, including 285 pRCC and 33 normal control samples [140]. MiR-29c-3p (miRNA), COL1A1 (protein-coding RNA), and H19 (lncRNA) were significantly correlated.…”

“…Furthermore, COL1A1 was negatively associated with M1 macrophage infiltration and positively related with infiltrating M2 macrophage, while H19 was positively linked with M2 macrophage infiltration, sug-gesting that the crosstalk between the H19-miR-29c-3p-COL1A1 axis and the infiltration of M1 and M2 macrophages can regulate pRCC development. Such axis might promote the polarization of M2 macrophages and inhibit M1 macrophage activation through the Wnt signaling pathway, co-operating in the pRCC tumorigenesis and leading to poor overall survival of pRCC patients [140].…”

“…GAS6-AS1 seems to be the most promising, as it was confirmed as a prognostic biomarker in five different studies. [134,136,[138][139][140][156][157][158][159]162,164,169,182,183].…”

A Novel Pyroptosis-Related Gene Signature for Predicting Prognosis in Kidney Renal Papillary Cell Carcinoma

“…Then, a high infiltration level of M2 macrophages was observed in the tumor microenvironment of KIRP, which was related to the immunosuppression state. Existing studies have demonstrated tumor-associated M2 macrophages could promote cell proliferation and angiogenesis and accelerate tumor progression ( Fan et al, 2021 ; Xie et al, 2021 ). This might be a part of reasons that KIRP patients obtained poor therapeutic effect from immune checkpoint inhibitors.…”