An Integrated Pan-Cancer Analysis of 33 Human Cancers Reveals the Potential Clinical Implications and Immunotherapeutic Value of C-X-C Motif Chemokine Ligand 13

Zhang, Huanyu; Yin, Honghao; Chen, Jing; Yuan, Yuan

doi:10.3389/fonc.2022.791962

Cited by 3 publications

(3 citation statements)

References 38 publications

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“…Previous studies have shown that TMB and MSI levels are critical biomarkers for the immunotherapy efficacy in cancer management [ 18 ]. Therefore, we further investigated the relation of RNF43 expression with MSI and TMB in different cancers.…”

Section: Resultsmentioning

confidence: 99%

Pan-cancer analysis identifies RNF43 as a prognostic, therapeutic and immunological biomarker

Xu,

Lin,

et al. 2023

Eur J Med Res

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Background RING finger protein 43 (RNF43), an E3 ubiquitin ligase, is a homologous gene mutated in several cancers. However, the pan-cancer panoramic picture of RNF43 and its predictive value for tumor immune phenotypes and immunotherapeutic efficacy are still largely unclear. Our study aims to clarify the functions of RNF43 in predicting the prognosis, immune signature, and immunotherapeutic efficacy in pan-cancer. Methods By using RNA-seq, mutation, and clinical data from the TCGA database, the expression levels and prognostic significance of RNF43 in pan-cancer were analyzed. The genetic alteration characteristics of RNF43 were displayed by the cBioPortal database. Gene Set Enrichment Analysis (GSEA) was performed to investigate the potential biological functions and signaling pathways modulated by RNF43 in cancers. The relationship of RNF43 expression with immune cell infiltration, and immune modulators expression was interpreted by the ESTIMATE algorithm, CIBERSORT algorithm, and TISIDB database. The correlations between RNF43, microsatellite instability (MSI), and tumor mutation burden (TMB) were also investigated. Furthermore, the predictive value of RNF43 for immunotherapeutic efficacy and drug sensitivity was further illustrated. Besides, immunohistochemistry (IHC) was employed to validate the expression of the RNF43 in different cancer types by our clinical cohorts, including patients with lung cancer, sarcoma, breast cancer, and kidney renal clear cell carcinoma. Results The results demonstrated that RNF43 was abnormally expressed in multiple cancers, and RNF43 is a critical prognosis-related factor in several cancers. RNF43 was frequently mutated in several cancers with a high frequency of 4%, and truncating mutation was the most frequent RNF43 mutation type. RNF43 expression was linked to the abundance of several immune cell types, including CD8+ T cells, B cells, and macrophages within the tumor immune microenvironment. Furthermore, RNF43 expression was significantly correlated with the efficacy of anti-PD-1/PD-L1 treatment, and it could predict the sensitivity of various anti-cancer drugs. Finally, IHC explored and validated the different expression levels of RNF43 in different cancers by our clinical samples. Conclusion Our results first present the expression pattern and the mutation signature of RNF43, highlighting that RNF43 is an important prognostic biomarker in pan-cancer. Furthermore, RNF43 seems to be a critical modulator in the tumor immune microenvironment and can function as a promising biomarker for predicting the immunotherapeutic efficacy of anti-PD-1/PD-L1 treatment, and drug sensitivity in cancer treatment.

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Section: Resultsmentioning

confidence: 99%

Pan-cancer analysis identifies RNF43 as a prognostic, therapeutic and immunological biomarker

Xu,

Lin,

et al. 2023

Eur J Med Res

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“…Its double-sided role in apoptosis remains to be explored and the mechanisms remain ambiguous. Furthermore, it is essential to acknowledge that CXCL13 might facilitate the onset, progression, and adverse prognosis of cancer by triggering additional oncogenic pathways, like the JAK-STAT pathway, via the chemokine pathway or cytokine receptor pathway (Zhang et al 2022 ). This may be related to the duality of the immune system in tumor progression (Ozga et al 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Transcriptome analysis reveals the clinical significance of CXCL13 in Pan-Gyn tumors

Ding,

Zhou,

Ding

et al. 2024

J Cancer Res Clin Oncol

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Background Gynecologic and breast tumors (Pan-Gyn) exhibit similar characteristics, and the role of CXCL13 in anti-tumor immunity and it’s potential as a biomarker for immune checkpoint blockade (ICB) therapy have been gradually revealed. However, the precise role of CXCL13 in Pan-Gyn remains unclear, lacking a systematic analysis. Methods We analyzed 2497 Pan-Gyn samples from the TCGA database, categorizing them into high and low CXCL13 expression groups. Validation was conducted using tumor expression datasets sourced from the GEO database. Correlation between CXCL13 and tumor immune microenvironment (TIME) was evaluated using multiple algorithms. Finally, we established nomograms for 3-year and 5-year mortality. Results High expression of CXCL13 in Pan-Gyn correlates with a favorable clinical prognosis, increased immune cell infiltration, and reduced intra-tumor heterogeneity. Model was assessed using the C-index [BRCA: 0.763 (0.732–0.794), UCEC: 0.821 (0.793–0.849), CESC: 0.736 (0.684–0.788), and OV: 0.728 (0.707–0.749)], showing decent prediction of discrimination and calibration. Conclusion Overall, this study provides comprehensive insights into the commonalities and differences of CXCL13 in Pan-Gyn, potentially opening new avenues for personalized treatment.

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“…Figure 1A-K clearly illustrates a signi cant elevation of PDXK expression in tumor tissue compared to normal tissue. Additionally, we examined PDXK expression levels across various human cancers using the TCGA database [27,28]. Notably, tumor tissues of COAD (Colon adenocarcinoma) and READ (Rectum adenocarcinoma) exhibited higher PDXK expression when compared to normal tissues (Fig.…”

Section: Pdxk Is Overexpressed In Crcmentioning

confidence: 99%

Pyridoxal kinase (PDXK) facilitates CRC progression by releasing beta-catenin from the GSK-3β destruction complex

fan,

Fan,

Gao

et al. 2023

Preprint

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Studies have suggested a close association between hyperactivation of the catenin beta 1 gene (CTNNB1) and the occurrence and progression of colorectal cancer (CRC). Here, we report that Pyridoxal kinase (PDXK) promotes the development of colorectal cancer through Wnt signaling pathway. The expression of PDXK is elevated in CRC patients and is associated with an unfavourable prognosis. Genetic depletion of PDXK significantly inhibited CRC cell viability, viability, and migration both in vitro and in vivo. Furthermore, we observed that overexpression of PDXK enhanced CRC cell viability, invasion, and migration, and these effects were dependent on its kinase activity. GSEA revealed a strong association between PDXK expression and the Wnt signaling pathway, which was validated through luciferase reporter assays and RT-qPCR. Mechanistically, PDXK was found to activate the Wnt signaling pathway by interacting with GSK-3β and releasing beta-catenin from the GSK-3β destruction complex, thereby promoting tumorigenesis. These findings provide direct insights into the molecular mechanisms underlying the functions of PDXK in CRC and suggest it as a potential therapeutic target for combating colorectal cancer.

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An Integrated Pan-Cancer Analysis of 33 Human Cancers Reveals the Potential Clinical Implications and Immunotherapeutic Value of C-X-C Motif Chemokine Ligand 13

Cited by 3 publications

References 38 publications

Pan-cancer analysis identifies RNF43 as a prognostic, therapeutic and immunological biomarker

Pan-cancer analysis identifies RNF43 as a prognostic, therapeutic and immunological biomarker

Transcriptome analysis reveals the clinical significance of CXCL13 in Pan-Gyn tumors

Pyridoxal kinase (PDXK) facilitates CRC progression by releasing beta-catenin from the GSK-3β destruction complex

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