Identification and validation of a cellular senescence-related lncRNA signature for prognostic prediction in patients with multiple myeloma

Zeng, Tanlun; Jiang, Sihan; Wang, Yichuan; Sun, Guanqun; Cao, Jinjin; Hu, Dingtao; Guang, Wang; Liang, Xijun; Ding, Jin; Du, Juan

doi:10.1080/15384101.2023.2213926

Cited by 4 publications

(2 citation statements)

References 61 publications

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“…A risk score model containing 9 disul dptosis-related prognostic lncRNAs was established using LASSO regression analysis. In previous studies, ATP2A1-AS1 was used to construct prognostic models related to cuproptosis and autophagy in cervical cancer and cellular senescence-related multiple myeloma [14][15][16] .…”

Section: Discussionmentioning

confidence: 99%

A novel disulfidptosis-related lncRNA signature in colorectal cancer for predicting prognosis, tumor immune microenvironment features and drug sensitivity

Qi,

Zhang,

et al. 2024

Preprint

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Colorectal cancer (CRC) is a common cancer with high mortality rates worldwide. Disulfidptosis is an emerging mode of cancer cell death. In this study, disulfidptosis-related lncRNAs were identified by screening and incorporated into a prognostic model to predict the prognosis and immunotherapy response of colorectal cancer (CRC), providing a new and effective guide for clinical decision making. Transcriptome and clinical data of CRC patients and normal controls were obtained from The Cancer Genome Atlas (TCGA). Pearson correlation, Cox and least absolute shrinkage and selection operator (LASSO) regression analyses were used to identify disulfidptosis-related lncRNAs. A risk scoring model was constructed, and its predictive performance was comprehensively validated. An accurate nomogram was constructed for CRC prognosis prediction. Model reliability was verified via principal component, survival and receiver operating characteristic (ROC) curve analyses. GO analysis and GSEA were used to identify cellular pathways relevant to the model. Immune cell infiltration was studied via the ESTIMATE and CIBERSORT algorithms. The association of tumor mutational burden (TMB) with the model-derived risk scores was assessed using single-nucleotide variant data. Finally, tThe clinical value of the model was evaluated through the GDSC and CTRP databases, and effective drugs were predicted. A prognostic risk model containing 9 disulfidptosis-related lncRNAs (ATP2A1-AS1, AC011815.1, AC013652.1, AC109992.2, AC069549.1, AC005034.5, SUCLG2-AS1, AP003555.1 and AL590101.1) was successfully constructed. There were significant difference in survival rates between the high-risk and low-risk groups (based on the median risk score) in the training and validation datasets. The risk score serves as an independent prognostic factor when combined with clinical variables. GSEA revealed that the high-risk group was enriched in the cellular processes of epidermis development, kidney differentiation and skin development. The prognostic model could stratify CRC patients into two distinct risk score groups. A high risk score independently predicted poor overall survival and was correlated with reduced immune cell infiltration, high TMB, and decreased tumor immune response activity. Immune checkpoint blockade might improve survival in high-risk CRC patients, whereas low-risk patients might be more responsive to targeted therapy and diverse kinase inhibitors. In summary, we established a disulfidptosis-related lncRNA model that holds promise as a reliable marker of CRC prognosis and immunotherapy response and can be also be used to predict the immune cell infiltration landscape and targeted therapy response.

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Section: Discussionmentioning

confidence: 99%

A novel disulfidptosis-related lncRNA signature in colorectal cancer for predicting prognosis, tumor immune microenvironment features and drug sensitivity

Qi,

Zhang,

et al. 2024

Preprint

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“…Zhang, Liang, Chen, et al found that AC009237.14 could be the prognostic biomarker for colon adenocarcinoma [39][40][41]. Zeng et al found that ATP2A1-AS1 could be a prognostic biomarker for patients with myeloma [42]. Feng et al found that ATP2A1-AS1 could be the prognostic biomarker for cervical cancer [43].…”

Section: Discussionmentioning

confidence: 99%

Prediction of Prognosis and Chemotherapeutic Sensitivity Based on Cuproptosis-Associated lncRNAs in Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma

Zhou

et al. 2023

Genes

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Cervical cancer is the fourth most common cancer. The 5-year survival rate for metastatic cervical cancer is less than 10%. The survival time of patients with recurrent cervical cancer is approximately 13–17 months. Cuproptosis is a novel type of cell death related to mitochondrial respiration. Accumulative studies showed that long non-coding RNAs (lncRNAs) regulated cervical cancer progression. Compressive bioinformatic analysis showed that nine cuproptosis-related lncRNAs (CRLs), including C002128.2, AC002563.1, AC009237.14, AC048337.1, AC145423.1, AL117336.1, AP001542.3, ATP2A1-AS1, and LINC00426, were independently correlated with the overall survival (OS) of cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) patients. The time-dependent area under curve value reached 0.716 at 1 year, 0.718 at 3 years, and 0.719 at 5 years. Notably, CESC patients in the low-risk group had increased immune cell infiltration and expression of several immune checkpoints, which indicated that they may benefit more from immune checkpoint blockade therapy. In addition, we also used the model for drug sensitivity analysis. Several drug sensitivities were more sensitive in high-risk patients and showed significant correlations with the risk models, such as Bortezomib_1191, Luminespib_1559, and Rapamycin_1084, suggesting that these drugs may be candidate clinical drugs for patients with a high risk of CESC. In summary, this study further explored the mechanism of CRLs in CESC and provided a more optimized prognostic model and some insights into chemotherapy of CESC.

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LINC01432binds to CELF2 in newly diagnosed multiple myeloma promoting short progression-free survival to standard therapy

Mishra,

Thunuguntla,

Perkin

et al. 2024

Preprint

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Multiple Myeloma (MM) is a highly prevalent and incurable form of cancer that arises from malignant plasma cells, with over 35,000 new cases diagnosed annually in the United States. While there are a growing number of approved therapies, MM remains incurable and nearly all patients will relapse and exhaust all available treatment options. Mechanisms for disease progression are unclear and in particular, little is known regarding the role of long non-coding RNAs (lncRNA) in mediating disease progression and response to treatment. In this study, we used transcriptome sequencing to compare newly diagnosed MM patients who had short progression- free survival (PFS) to standard first-line treatment (PFS < 24 months) to patients who had prolonged PFS (PFS > 24 months). We identified 157 differentially upregulated lncRNAs with short PFS and focused our efforts on characterizing the most upregulated lncRNA,LINC01432. We investigatedLINC01432overexpression and CRISPR/Cas9 knockdown in MM cell lines to show thatLINC01432overexpression significantly increases cell viability and reduces apoptosis, while knockdown significantly reduces viability and increases apoptosis, supporting the clinical relevance of this lncRNA. Next, we used individual-nucleotide resolution cross-linking immunoprecipitation with RT-qPCR to show thatLINC01432directly interacts with the RNA binding protein, CELF2. Lastly, we showed thatLINC01432-targeted locked nucleic acid antisense oligonucleotides reduce viability and increases apoptosis. In summary, this fundamental study identified lncRNAs associated with short PFS to standard NDMM treatment and further characterizedLINC01432,which inhibits apoptosis.Key points:lncRNA expression was found to be dysregulated in patients with short PFS to standard multiple myeloma therapy.LINC01432-bound CELF2 inhibits apoptosis.

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Identification and validation of a cellular senescence-related lncRNA signature for prognostic prediction in patients with multiple myeloma

Cited by 4 publications

References 61 publications

A novel disulfidptosis-related lncRNA signature in colorectal cancer for predicting prognosis, tumor immune microenvironment features and drug sensitivity

A novel disulfidptosis-related lncRNA signature in colorectal cancer for predicting prognosis, tumor immune microenvironment features and drug sensitivity

Prediction of Prognosis and Chemotherapeutic Sensitivity Based on Cuproptosis-Associated lncRNAs in Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma

LINC01432binds to CELF2 in newly diagnosed multiple myeloma promoting short progression-free survival to standard therapy

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