The m6A-Related Long Noncoding RNA Signature Predicts Prognosis and Indicates Tumor Immune Infiltration in Ovarian Cancer

Geng, Rui; Chen, Tian; Zhong, Zihang; Ni, Senmiao; Bai, Jianling; Liu, Jinhui

doi:10.3390/cancers14164056

Cited by 12 publications

(8 citation statements)

References 74 publications

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“…These findings imply that WAC-AS1 is downregulated with the occurrence and development of brain glioma, and no longer plays a protective role in the prognosis of this disease. WAC-AS1 has been identified as a protective factor in ovarian carcinoma, which contrasts with our results [ 9 , 24 ]. Although we observed a similar trend for a protective role of WAC-AS1 in patients with OV, the Kaplan–Meier survival analysis indicated that there was no significant difference in survival between patients with high and low WAC-AS1 expression.…”

Section: Discussioncontrasting

confidence: 99%

LncRNA WAC-AS1 expression in human tumors correlates with immune infiltration and affects prognosis

2023

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Background WAC-antisense RNA1 (WAC-AS1) is a newly identified long non-coding RNA (lncRNA) implicated in the prognosis and development of a few types of tumors. However, the correlations of WAC-AS1 with immune infiltration and patient prognosis in pan-cancer remain unclear. In the present study, we aimed to investigate the prognostic value and immunological functions of WAC-AS1 across 33 different types of cancers. Methods To investigate the potential oncogenic roles of WAC-AS1, bioinformatics analyses were performed using the Cancer Genome Atlas (TCGA) and Genotype Tissue-Expression (GTEx) datasets. The correlations of WAC-AS1 with prognosis, clinical phenotype, tumor mutational burden (TMB), microsatellite instability (MSI), tumor regulation-related genes, tumor microenvironment, immune cell infiltration, and drug resistance to commonly used chemotherapy drugs in different types of tumors were explored. Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) were performed to explore the biological functions of WAC-AS1 in tumors. In situ hybridization (ISH) was performed in tissue microarray (TMA) to confirm the expression of WAC-AS1 in multiple tumor tissues. Results WAC-AS1 showed aberrant expression in most cancers when compared to the normal tissues. It also has prognostic value in multiple types of cancers. Elevated WAC-AS1 expression was associated with poor prognosis and overall survival in adrenocortical carcinoma (ACC), breast invasive carcinoma (BRCA), and liver hepatocellular carcinoma (LIHC). A significant negative correlation between WAC-AS1 expression and overall survival was observed in brain lower-grade glioma (LGG), pancreatic adenocarcinoma (PAAD), and skin cutaneous melanoma (SKCM). The expression of WAC-AS1 also showed a correlation with clinical stage in six types of tumors, and with tumor mutational burden and microsatellite instability in several different types of cancers. The immune scores of those cancers were found to be significant. Additionally, the effectiveness of fluorouracil and four other anticancer drugs was significantly different based on the expression of WAC-AS1 in these cancers. Moreover, the ISH results showed in six types of tumors, the expression of WAC-AS1 was consistent with the Pan-cancer analysis using TCGA and GTEx database. Conclusions These results indicate an intensive involvement of WAC-AS1 in the regulation of immune responses, immune cell infiltration, and malignant properties in various types of cancers, suggesting that WAC-AS1 may serve as a prognostic marker across diverse types of cancers.

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Section: Discussioncontrasting

confidence: 99%

LncRNA WAC-AS1 expression in human tumors correlates with immune infiltration and affects prognosis

2023

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“…AL122125.1 emerged as an independent prognostic factor, providing novel information about LUSC risk-stratification ( 63 ). Similar approach has also been applied for the analysis of bladder, colon cancers, hepatocellular carcinoma and hematological malignancies, in particular like acute myelocytic leukemia ( 28 , 64 – 73 , 77 , 78 ).…”

Section: M6a-related Lncrnas Signaturesmentioning

confidence: 99%

The lncRNA epigenetics: The significance of m6A and m5C lncRNA modifications in cancer

et al. 2023

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Most of our transcribed RNAs are represented by non-coding sequences. Long non-coding RNAs (lncRNAs) are transcripts with no or very limited protein coding ability and a length >200nt. They can be epigenetically modified. N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), 7-methylguanosine (m7G) and 2’-O-methylation (Nm) are some of the lncRNAs epigenetic modifications. The epigenetic modifications of RNA are controlled by three classes of enzymes, each playing a role in a specific phase of the modification. These enzymes are defined as “writers”, “readers” and “erasers”. m6A and m5C are the most studied epigenetic modifications in RNA. These modifications alter the structure and properties, thus modulating the functions and interactions of lncRNAs. The aberrant expression of several lncRNAs is linked to the development of a variety of cancers and the epigenetic signatures of m6A- or m5C-related lncRNAs are increasingly recognized as potential biomarkers of prognosis, predictors of disease stage and overall survival. In the present manuscript, the most up to date literature is reviewed with the focus on m6A and m5C modifications of lncRNAs and their significance in cancer.

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“…When integrated with clinical characteristics, the model exhibited enhanced predictive efficacy compared to the standalone signature (Figure 5). Notably, among clinical characteristics integrated prognostic signatures, this signature exhibits a high AUC value of ROC curve, surpassing the predictive performance of both the endoplasmic reticulum stressrelated gene signature and the m6A-related lncRNA signature in OV [41,42]. In summary, the ubiquitin-related signature showed a satisfactory prognostic value for patients with OV.…”

Section: Advances Of the Ubrgs Signature For Prognostic Prediction In Ovmentioning

confidence: 87%

Identification of a Prognostic Signature for Ovarian Cancer Based on Ubiquitin-Related Genes Suggesting a Potential Role for FBXO9

Luo,

Wang,

Zhang

et al. 2023

Biomolecules

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Background: Ovarian cancer (OV) is associated with high mortality and poses challenges in diagnosis and prognosis prediction. Ubiquitin-related genes (UbRGs) are involved in the initiation and progression of cancers, but have still not been utilized for diagnosis and prognosis of OV. Methods: K48-linked ubiquitination in ovarian tissues from our OV and control cohort was assessed using immunohistochemistry. UbRGs, including ubiquitin and ubiquitin-like regulators, were screened based on the TCGA-OV and GTEx database. Univariate Cox regression analysis identified survival-associated UbRGs. A risk model was established using the LASSO regression and multivariate Cox regression analysis. The relationship between UbRGs and immune cell infiltration, tumor mutational burden, drug sensitivity, and immune checkpoint was determined using the CIBERSORT, ESTIMATE, and Maftools algorithms, based on the Genomics of Drug Sensitivity in Cancer and TCGA-OV databases. GEPIA2.0 was used to analyze the correlation between FBXO9/UBD and DNA damage repair-related genes. Finally, FBXO9 and UBD were accessed in tissues or cells using immunohistochemistry, qPCR, and Western blot. Results: We confirmed the crucial role for ubiquitination in OV as a significant decrease of K48-linked ubiquitination was observed in primary OV lesions. We identified a prognostic signature utilizing two specific UbRGs, FBXO9 and UBD. The risk score obtained from this signature accurately predicted the overall survival of TCGA-OV training dataset and GSE32062 validation dataset. Furthermore, this risk score also showed association with immunocyte infiltration and drug sensitivity, revealing potential mechanisms for ubiquitination mediated OV risk. In addition, FBXO9, but not UBD, was found to be downregulated in OV and positively correlated with DNA damage repair pathways, suggesting FBXO9 as a potential cancer suppressor, likely via facilitating DNA damage repair. Conclusions: We identified and validated a signature of UbRGs that accurately predicts the prognosis, offers valuable guidance for optimizing chemotherapy and targeted therapies, and suggests a potential role for FBXO9 in OV.

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The m6A-Related Long Noncoding RNA Signature Predicts Prognosis and Indicates Tumor Immune Infiltration in Ovarian Cancer

Cited by 12 publications

References 74 publications

LncRNA WAC-AS1 expression in human tumors correlates with immune infiltration and affects prognosis

LncRNA WAC-AS1 expression in human tumors correlates with immune infiltration and affects prognosis

The lncRNA epigenetics: The significance of m6A and m5C lncRNA modifications in cancer

Identification of a Prognostic Signature for Ovarian Cancer Based on Ubiquitin-Related Genes Suggesting a Potential Role for FBXO9

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