Construction of Two Alternative Polyadenylation Signatures to Predict the Prognosis of Sarcoma Patients

Hu, Chuan; Liu, Chuan; Li, Jianyi; Yu, Tengbo; Dong, Jun; Chen, Bin; Du, Yukun; Tang, Xiaojie; Xi, Yongming

doi:10.3389/fcell.2021.595331

Cited by 6 publications

(4 citation statements)

References 51 publications

(76 reference statements)

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“…Shortened 3′UTR of SMC1A was seen in lung adenocarcinoma and had a significant association with clinical prognosis 43 . Hu et al have constructed two APA signatures for predicting OS and progress free-survival (PFS) of patients with sarcoma by the similar approaches to this study 44 . Notably, another study from our group that used a similar approach to build APAs signatures to predict OS and recurrence-free survival in breast cancer patients, suggesting more general prognostic roles for APAs 45 .…”

Section: Discussionmentioning

confidence: 99%

Alternative polyadenylation associated with prognosis and therapy in colorectal cancer

Zhang

Wang

2022

Sci Rep

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Colorectal cancer (CRC) is among the most widely spread cancers globally. Aberrant alternative polyadenylation (APA) plays a role in cancer onset and its progression. Consequently, this study focused on highlighting the role of APA events and signals in the prognosis of patients with CRC. The APA events, RNA sequencing (RNA-seq), somatic mutations, copy number variants (CNVs), and clinical information of the CRC cohort were obtained from The Cancer Genome Atlas (TCGA) database and UCSC (University of California-Santa Cruz) Xena database. The whole set was sorted into two sets: a training set and a test set in a ratio of 7:3. 197 prognosis-related APA events were collected by performing univariate Cox regression signature in patients with CRC. Subsequently, a signature for APA events was established by least absolute shrinkage and selection operator (LASSO) and multivariate Cox analysis. The risk scores were measured for individual patients on the basis of the signature and patients were sorted into two groups; the high-risk group and the low-risk group as per their median risk scores. Kaplan–Meier curves, principal component analysis (PCA), and time-dependent receiver operator characteristic (ROC) curves revealed that the signature was able to predict patient prognosis effectively and further validation was provided in the test set and the whole set. The high-risk and low-risk groups displayed various distributions of mutations and CNVs. Tumor mutation burden (TMB) alone and in combination with the signature predicted the prognosis of CRC patients, but the gene frequencies of TMBs and CNVs did not change in the low- and high-risk groups. Moreover, immunotherapy and chemotherapy treatments showed different responses to PD-1 inhibitors and multiple chemotherapeutic agents in the low and high-risk groups based on the tumor immune dysfunction and exclusion (TIDE) and genomics of drugs sensitivity in cancer (GDSC) databases. This study may help in understanding the potential roles of APA in CRC, and the signature for prognosis-related APA events can work as a potential predictor for survival and treatment in patients with CRC.

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Section: Discussionmentioning

confidence: 99%

Alternative polyadenylation associated with prognosis and therapy in colorectal cancer

Zhang

Wang

2022

Sci Rep

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“…The 3′ end-processing machinery refers to multiple APA factors, including CPSF, CSTF, CFI, etc. [ 14 , 15 , 16 ]. To explore which APA factor(s) probably mediate those differential APA events between responders and non-responders in melanoma, we recruited 98 key APA factors via literature screening ( Table S10 ) and performed a correlation analysis between those APA factors and differential APA events.…”

Section: Resultsmentioning

confidence: 99%

“…Recently, oncologists have been focusing on the discovery of effective biomarkers for predicting outcomes and guiding precision medicine [ 28 , 29 , 30 ]. APA has been reported to have a strong predictive ability for the prognosis of cancer patients [ 6 , 16 , 18 ]. However, relatively few APA events have been reported for the prediction of immunotherapy [ 5 ], especially in melanoma.…”

Section: Discussionmentioning

confidence: 99%

The Transcriptional Landscape of Immune-Response 3′-UTR Alternative Polyadenylation in Melanoma

Yang,

Wu,

Chen

et al. 2024

IJMS

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The prognosis of patients with malignant melanoma has been improved in recent decades due to advancements in immunotherapy. However, a considerable proportion of patients are refractory to treatment, particularly at advanced stages. This underscores the necessity of developing a new strategy to improve it. Alternative polyadenylation (APA), as a marker of crucial posttranscriptional regulation, has emerged as a major new type of epigenetic marker involved in tumorigenesis. However, the potential roles of APA in shaping the tumor microenvironment (TME) are largely unexplored. Herein, we collected two cohorts comprising melanoma patients who received immune checkpoint inhibitor (ICI) immunotherapy to quantify transcriptome-wide discrepancies in APA. We observed a global change in 3′-UTRs between responders and non-responders, which might involve DNA damage response, angiogenesis, PI3K-AKT signaling pathways, etc. Ten putative master APA regulatory factors for those APA events were detected via a network analysis. Notably, we established an immune response-related APA scoring system (IRAPAss), which exhibited a great performance of predicting immunotherapy response in multiple cohorts. Furthermore, we examined the correlation of APA with TME at the single-cell level using four single-cell immune profiles of tumor-infiltrating lymphocytes (TILs), which revealed an overall discrepancy in 3′-UTR length across diverse T cell populations, probably contributing to immunoregulation in melanoma. In conclusion, our study provides a transcriptional landscape of APA implicated in immunoregulation, which might lay the foundation for developing a new strategy for improving immunotherapy response for melanoma patients by targeting APA.

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“…As for the immune status, we adopted the ImmuCellAI method to calculate the infiltration of immune cells in KIRC samples. This method supported the ssGSEA enrichment score of expression deviation profile per cell type and has been widely used in cancer research, including pituitary adenomas, hepatocellular carcinoma, sarcoma, and lung adenocarcinoma ( Wang et al, 2020a ; Zhang et al, 2020b ; Hu et al, 2021 ; Zhao et al, 2021 ). We successfully clustered the KIRC patients into different groups by hypoxia and immune status using these combined methods.…”

Section: Discussionmentioning

confidence: 98%

Identification of Hypoxia–Immune-Related Gene Signatures and Construction of a Prognostic Model in Kidney Renal Clear Cell Carcinoma

Bai

Chen

Yan

et al. 2022

Front. Cell Dev. Biol.

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Introduction: Kidney renal clear cell carcinoma (KIRC), a kind of malignant disease, is a severe threat to public health. Tracking the information of tumor progression and conducting a related dynamic prognosis model are necessary for KIRC. It is crucial to identify hypoxia–immune-related genes and construct a prognostic model due to immune interaction and the influence of hypoxia in the prognosis of patients with KIRC.Methods: The hypoxia and immune status of KIRC patients were identified by utilizing t-SNE and ImmuCellAI for gene expression data. COX and Lasso regression were used to identify some hypoxia–immune-related signature genes and further construct a prognostic risk model based on these genes. Internal and external validations were also conducted to construct a prognostic model. Finally, some potentially effective drugs were screened by the CMap dataset.Results: We found that high-hypoxia and low-immune status tend to induce poor overall survival (OS). Six genes, including PLAUR, UCN, PABPC1L, SLC16A12, NFE2L3, and KCNAB1, were identified and involved in our hypoxia–immune-related prognostic risk model. Internal verification showed that the area under the curve (AUC) for the constructed models for 1-, 3-, 4-, and 5-year OS were 0.768, 0.754, 0.775, and 0.792, respectively. For the external verification, the AUC for 1-, 3-, 4-, and 5-year OS were 0.768, 0.739, 0.763, and 0.643 respectively. Furthermore, the decision curve analysis findings demonstrated excellent clinical effectiveness. Finally, we found that four drugs (including vorinostat, fludroxycortide, oxolinic acid, and flutamide) might be effective and efficient in alleviating or reversing the status of severe hypoxia and poor infiltration of immune cells.Conclusion: Our constructed prognostic model, based on hypoxia–immune-related genes, has excellent effectiveness and clinical application value. Moreover, some small-molecule drugs are screened to alleviate severe hypoxia and poor infiltration of immune cells.

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Construction of Two Alternative Polyadenylation Signatures to Predict the Prognosis of Sarcoma Patients

Cited by 6 publications

References 51 publications

Alternative polyadenylation associated with prognosis and therapy in colorectal cancer

Alternative polyadenylation associated with prognosis and therapy in colorectal cancer

The Transcriptional Landscape of Immune-Response 3′-UTR Alternative Polyadenylation in Melanoma

Identification of Hypoxia–Immune-Related Gene Signatures and Construction of a Prognostic Model in Kidney Renal Clear Cell Carcinoma

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