Immune Checkpoint Inhibitors in Uro-Oncology: Urgent Call for Biomarkers

Pichler, Renate

doi:10.3390/cancers12102768

Cited by 2 publications

(3 citation statements)

References 23 publications

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“…A total of 30 matched tumor/normal tissue samples were collected from patients with ccRCC in the operating room of the First Affiliated Hospital of Anhui Medical University (Hefei, China). The inclusion criteria of tissue specimens included as follows: ( 1 ) pathological diagnosis for ccRCC; ( 2 ) except ccRCC with no other malignancy; ( 3 ) consistent with radical nephrectomy or partial nephrectomy indications; ( 4 ) no radiotherapy and chemotherapy before surgery. All patients signed informed consent forms before surgery, and pathological diagnosis of ccRCC was confirmed by two senior pathologists from our institution, after surgery.…”

Section: Methodsmentioning

confidence: 99%

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Construction of Competitive Endogenous RNA Network and Verification of 3-Key LncRNA Signature Associated With Distant Metastasis and Poor Prognosis in Patients With Clear Cell Renal Cell Carcinoma

Zhang

Tang

et al. 2021

Front. Oncol.

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Clear cell renal cell carcinoma (ccRCC) is a common malignancy with high distant metastasis rate. Long non-coding RNAs (LncRNAs) are reported to be upregulated or downregulated in multiple cancers and play a crucial role in the metastasis of tumors or prognosis. Therefore, the purpose of our study is to construct a prognostic signature for ccRCC based on distant metastasis-related lncRNAs and explore the involved potential competitive endogenous RNA (ceRNA) network. The differentially expressed genes (DEGs) screened from the database of the cancer genome atlas (TCGA) were used to construct a co-expression network and identify the distant metastasis-related module by weighted gene co-expression network analysis (WGCNA). Key genes with metastatic and prognostic significance were identified through rigorous screening, including survival analysis, correlation analysis, and expression analyses in stage, grade, and distant metastasis, and were verified in the data set of gene expression omnibus (GEO) and the database from gene expression profiling interactive analysis (GEPIA). The potential upstream miRNAs and lncRNAs were predicted via five online databases and LncBase. Here, we constructed a ceRNA network of key genes that are significantly associated with the distant metastasis and prognosis of patients with ccRCC. The distant metastasis-related lncRNAs were used to construct a risk score model through the univariate, least absolute shrinkage selection operator (LASSO), and multivariate Cox regression analyses, and the patients were divided into high- and low-risk groups according to the median of the risk score. The Kaplan–Meier survival analysis demonstrated that mortality was significantly higher in the high-risk group than in the low-risk group. Considering the other clinical phenotype, the Cox regression analyses indicated that the lncRNAs model could function as an independent prognostic factor. Quantitative real-time (qRT)-PCR in the tissues and cells of ccRCC verified the high-expression level of three lncRNAs. Gene set enrichment analysis (GSEA) revealed that the lncRNA prognostic signature was mainly enriched in autophagy- and immune-related pathways, indicating that the autophagy and immune functions may play an important role in the distant metastasis of ccRCC. In summary, the constructed distant metastasis-related lncRNA signature could independently predict prognosis in patients with ccRCC, and the related ceRNA network provided a new sight on the potential mechanism of distant metastasis and a promising therapeutic target for ccRCC.

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Section: Methodsmentioning

confidence: 99%

“…Renal cell carcinoma (RCC), the third most common malignancy of the urinary system, also belongs to the ninth most common cancer, worldwide ( 1 ). It is estimated that RCC accounts for 73,750 new cases and 14,830 death cases in the United States in 2020 ( 2 ).…”

Section: Introductionmentioning

confidence: 99%

Construction of Competitive Endogenous RNA Network and Verification of 3-Key LncRNA Signature Associated With Distant Metastasis and Poor Prognosis in Patients With Clear Cell Renal Cell Carcinoma

Zhang

Tang

et al. 2021

Front. Oncol.

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“…Renal cell carcinoma (RCC) is one of the most common malignancies of the urological system [ 1 ]. Clear cell renal cell carcinoma (ccRCC) is the most common type of malignant renal tumor with more malignant features and poor prognosis, accounting for most RCC-associated deaths [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of Novel Prognostic Signatures for Clear Cell Renal Cell Carcinoma Based on ceRNA Network Construction and Immune Infiltration Analysis

Zhou

Wen

et al. 2022

Disease Markers

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Objective. Clear cell renal cell carcinoma (ccRCC) carries significant morbidity and mortality globally and is often resistant to conventional radiotherapy and chemotherapy. Immune checkpoint blockade (ICB) has received attention in ccRCC patients as a promising anticancer treatment. Furthermore, competitive endogenous RNA (ceRNA) networks are crucial for the occurrence and progression of various tumors. This study was aimed at identifying reliable prognostic signatures and exploring potential mechanisms between ceRNA regulation and immune cell infiltration in ccRCC patients. Methods and Results. Gene expression profiling and clinical information of ccRCC samples were obtained from The Cancer Genome Atlas (TCGA) database. Through comprehensive bioinformatic analyses, differentially expressed mRNAs (DEmRNAs; n = 131 ), lncRNAs (DElncRNAs; n = 12 ), and miRNAs (DEmiRNAs; n = 25 ) were identified to establish ceRNA networks. The CIBERSORT algorithm was applied to calculate the proportion of 22 types of tumor-infiltrating immune cells (TIICs) in ccRCC tissues. Subsequently, univariate Cox, Lasso, and multivariate Cox regression analyses were employed to construct ceRNA-related and TIIC-related prognostic signatures. In addition, we explored the relationship between the crucial genes and TIICs via coexpression analysis, which revealed that the interactions between MALAT1, miR-1271-5p, KIAA1324, and follicular helper T cells might be closely correlated with the progression of ccRCC. Ultimately, we preliminarily validated that the potential MALAT1/miR-1271-5p/KIAA1324 axis was consistent with the ceRNA theory by qRT-PCR in the ccRCC cell lines. Conclusion. On the basis of the ceRNA networks and TIICs, we constructed two prognostic signatures with excellent predictive value and explored possible molecular regulatory mechanisms, which might contribute to the improvement of prognosis and individualized treatment for ccRCC patients.

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Immune Checkpoint Inhibitors in Uro-Oncology: Urgent Call for Biomarkers

Abstract: Bladder cancer and renal cell carcinoma (RCC) are the second and third most commonly diagnosed cancers in the field of uro-oncology [...]

Cited by 2 publications

References 23 publications

Construction of Competitive Endogenous RNA Network and Verification of 3-Key LncRNA Signature Associated With Distant Metastasis and Poor Prognosis in Patients With Clear Cell Renal Cell Carcinoma

Construction of Competitive Endogenous RNA Network and Verification of 3-Key LncRNA Signature Associated With Distant Metastasis and Poor Prognosis in Patients With Clear Cell Renal Cell Carcinoma

Identification of Novel Prognostic Signatures for Clear Cell Renal Cell Carcinoma Based on ceRNA Network Construction and Immune Infiltration Analysis

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