Emerging Biomarkers for Predicting Bladder Cancer Lymph Node Metastasis

Zhang, Chunyu; Hu, Jiao; Li, Huihuang; Othmane, Belaydi; Ren, Wen; Yi, Zhenglin; Qiu, Dongxu; Ou, Zhenyu; Chen, Jinbo; Zu, Xiongbing

doi:10.3389/fonc.2021.648968

Cited by 13 publications

(13 citation statements)

References 125 publications

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“…Furthermore, because of the different causative molecules, although some patients have the same TNM stage or similar risk factors, they may have different clinical outcomes. Therefore, molecular biomarkers to predict tumor prognosis are of great importance [ 24 , 25 ]. Ferroptosis may be associated with biological behaviors such as proliferation, invasion, and metastasis in BC [ 6 , 7 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of a Nomogram from Ferroptosis-Related Long Noncoding RNAs Signature to Analyze Overall Survival in Patients with Bladder Cancer

Cui

Chai

Che

et al. 2021

Journal of Oncology

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Purpose. This study aimed to establish a nomogram to predict the overall survival (OS) of patients with bladder cancer (BC) by ferroptosis-related long noncoding RNAs (FRlncRNAs) signature. Methods. We obtained FRlncRNAs expression profiles and clinical data of patients with BC from the Cancer Genome Atlas database. The patients were divided into the training set, testing set, and overall set. Lasso regression and multivariate Cox regression were used to establish the FRlncRNAs signature, the prognosis of each group was compared by Kaplan–Meier (K-M) analysis, and the receiver operating characteristic (ROC) curve evaluated the accuracy of the model. The Gene Set Enrichment Analysis (GSEA) was used for the visualization of the functional enrichment for FRlncRNAs. The databases of GEPIA and K-M Plotter were used for subsequent functional analysis of major FRlncRNAs. Results. Thirteen prognostic FRlncRNAs (LINC00942, MAFG-DT, AL049840.3, AL136084.3, OCIAD1-AS1, AC062017.1, AC008074.2, AC018653.3, AL031775.1, USP30-AS1, LINC01767, AC132807.2, and AL354919.2) were identified to be significantly different, constituting an FRlncRNAs signature. Patients with BC were divided into low-risk group and high-risk group by this signature in the training, testing, and overall sets. K-M analysis showed that the prognosis of patients in the high-risk group was poor and the difference in the subgroup analyses was statistically significant. ROC analysis revealed that the predictive ability of the model was more accurate than traditional assessment methods. A risk score based on FRlncRNAs signature was an independent prognostic factor for the patients with BC (HR = 1.388, 95%CI = 1.228–1.568, P < 0.001 ). Combining the FRlncRNAs signature and clinicopathological factors, a predictive nomogram was constructed. The nomogram can accurately predict the overall survival of patients and had high clinical practicability. The GSEA analysis showed that the primary pathways were WNT, MAPK, and cell-matrix adhesion signaling pathways. The major FRlncRNAs (MAFG-DT) were associated with poor prognosis in the GEPIA and K-M Plotter database. Conclusion. Thirteen prognostic FRlncRNAs and their nomogram were accurate tools for predicting the OS of BC, which might be molecular biomarkers and therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Identification of a Nomogram from Ferroptosis-Related Long Noncoding RNAs Signature to Analyze Overall Survival in Patients with Bladder Cancer

Cui

Chai

Che

et al. 2021

Journal of Oncology

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“…In fact, many new treatment strategies have been proposed to improve outcomes and suppress adverse events in these patients (7,8). Furthermore, the identification of better predictive markers for BC recurrence and metastasis is important, and many investigators pay special attention to this issue (9)(10)(11).…”

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confidence: 99%

Ceruloplasmin Levels in Cancer Tissues and Urine Are Significant Biomarkers of Pathological Features and Outcome in Bladder Cancer

et al. 2021

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Background/Aim: Α previous report showed that immune complex-ceruloplasmin (CP) in urine is associated with carcinogenesis and malignant behavior in bladder cancer (BC). We investigated the pathological significance and prognostic roles of urine and tissue levels of CP protein in BC patients. Materials and Methods: Urine CP levels were measured using an enzyme-linked immunosorbent assay in 97 patients. CP expression in BC tissues was evaluated by immunohistochemical analysis in 176 patient samples. Results: Urine CP levels were positively associated with tumor grade and pT stage in non-muscle invasive BC (NMIBC). CP expression in BC tissues was positively associated with tumor growth and progression. Multivariate analysis demonstrated that high urine CP levels was an independent predictor of recurrence in the urinary tract in NMIBC (hazard ratio=2.87, p=0.016). Conclusion: CPrelated markers, especially urine CP levels, are useful biomarkers of malignant potential and prognosis in NMIBC.

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“…Different from YTHDF that may accelerate mRNA decay [ 27 ], IGF2BPs, as newly identified m6A readers, can target numerous mRNAs and maintain their stability to promote cancer progression and metastasis in a m6A-dependent manner [ 28 , 29 ]. Several recent studies have reported that m6A modification is implicated in lymphatic metastasis in cancers [ 30 – 32 ]. However, the functional roles of IGF2BP2 in HNSCC, and more specifically whether IGF2BP2 regulates lymphatic metastasis in HNSCC by modifying m6A is currently unclear.…”

Section: Introductionmentioning

confidence: 99%

RNA N6-methyladenosine reader IGF2BP2 promotes lymphatic metastasis and epithelial-mesenchymal transition of head and neck squamous carcinoma cells via stabilizing slug mRNA in an m6A-dependent manner

Pan

et al. 2022

J Exp Clin Cancer Res

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Background Lymph node metastasis is the main cause of poor prognosis of head and neck squamous carcinoma (HNSCC) patients. N6-methyladenosine (m6A) RNA modification is an emerging epigenetic regulatory mechanism for gene expression, and as a novel m6A reader protein, IGF2BP2 has been implicated in tumor progression and metastasis. However, not much is currently known about the functional roles of IGF2BP2 in HNSCC, and whether IGF2BP2 regulates lymphatic metastasis through m6A modification in HNSCC remains to be determined. Methods The expression and overall survival (OS) probability of m6A-related regulators in HNSCC were analyzed with The Cancer Genome Atlas (TCGA) dataset and GEPIA website tool, respectively. The expression levels of IGF2BP2 were measured in HNSCC tissues and normal adjacent tissues. To study the effects of IGF2BP2 on HNSCC cell metastasis in vitro and in vivo, gain- and loss- of function methods were employed. RIP, MeRIP, luciferase reporter and mRNA stability assays were performed to explore the epigenetic mechanism of IGF2BP2 in HNSCC. Results We investigated 20 m6A-related regulators in HNSCC and discovered that only the overexpression of IGF2BP2 was associated with a poor OS probability and an independent prognostic factor for HNSCC patients. Additionally, we demonstrated that IGF2BP2 was overexpressed in HNSCC tissues, and significantly correlated to lymphatic metastasis and poor prognosis. Functional studies have shown that IGF2BP2 promotes both HNSCC cell migration as well as invasion via the epithelial-mesenchymal transition (EMT) process in vitro, and IGF2BP2 knockdown significantly inhibited lymphatic metastasis and lymphangiogenesis in vivo. Mechanistic investigations revealed that Slug, a key EMT-related transcriptional factor, is the direct target of IGF2BP2, and essential for IGF2BP2-regulated EMT and metastasis in HNSCC. Furthermore, we demonstrated that IGF2BP2 recognizes and binds the m6A site in the coding sequence (CDS) region of Slug and promotes its mRNA stability. Conclusions Collectively, our study uncovers the oncogenic role and potential mechanism of IGF2BP2, which serves as a m6A reader, in controlling lymphatic metastasis and EMT in HNSCC, suggesting that IGF2BP2 may act as a therapeutic target and prognostic biomarker for HNSCC patients with metastasis.

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Emerging Biomarkers for Predicting Bladder Cancer Lymph Node Metastasis

Cited by 13 publications

References 125 publications

Identification of a Nomogram from Ferroptosis-Related Long Noncoding RNAs Signature to Analyze Overall Survival in Patients with Bladder Cancer

Identification of a Nomogram from Ferroptosis-Related Long Noncoding RNAs Signature to Analyze Overall Survival in Patients with Bladder Cancer

Ceruloplasmin Levels in Cancer Tissues and Urine Are Significant Biomarkers of Pathological Features and Outcome in Bladder Cancer

RNA N6-methyladenosine reader IGF2BP2 promotes lymphatic metastasis and epithelial-mesenchymal transition of head and neck squamous carcinoma cells via stabilizing slug mRNA in an m6A-dependent manner

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