Dataset Information

Crosstalk of Oxidative Phosphorylation-Related Subtypes, Establishment of a Prognostic Signature and Immune Infiltration Characteristics in Colorectal Adenocarcinoma.

ABSTRACT: Oxidative phosphorylation (OXPHOS) is an emerging target in cancer therapy. However, the prognostic signature of OXPHOS in colorectal adenocarcinoma (COAD) remains non-existent. We comprehensively investigated the expression pattern of OXPHOS-related genes (ORGs) in COAD from public databases. Based on four ORGs, an OXPHOS-related prognostic signature was established in which COAD patients were assigned different risk scores and classified into two different risk groups. It was observed that the low-risk group had a better prognosis but lower immune activities including immune cells and immune-related function in the tumor microenvironment. Combining with relevant clinical features, a nomogram for clinical application was also established. Receiver operating characteristic (ROC) and calibration curves were constructed to demonstrate the predictive ability of this risk signature. Moreover, a higher risk score was significantly positively correlated with higher tumor mutation burden (TMB) and generally higher gene expression of immune checkpoint, N6-methyladenosine (m6A) RNA methylation regulators and mismatch repair (MMR) related proteins. The results also indicated that the high-risk group was more sensitive to immunotherapy and certain chemotherapy drugs. In conclusion, OXPHOS-related prognostic signature can be utilized to better understand the roles of ORGs and offer new perspectives for clinical prognosis and personalized treatment.

SUBMITTER: Wang C

PROVIDER: S-EPMC9496738 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Crosstalk of Oxidative Phosphorylation-Related Subtypes, Establishment of a Prognostic Signature and Immune Infiltration Characteristics in Colorectal Adenocarcinoma.

Wang Can C Cui Guoliang G Wang Dan D Wang Min M Chen Qi Q Wang Yunshan Y Lu Mengjie M Tang Xinyi X Yang Bolin B

Cancers 20220916 18

Oxidative phosphorylation (OXPHOS) is an emerging target in cancer therapy. However, the prognostic signature of OXPHOS in colorectal adenocarcinoma (COAD) remains non-existent. We comprehensively investigated the expression pattern of OXPHOS-related genes (ORGs) in COAD from public databases. Based on four ORGs, an OXPHOS-related prognostic signature was established in which COAD patients were assigned different risk scores and classified into two different risk groups. It was observed that the ...[more]

PMID: 36139663

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Project description:BackgroundColorectal adenocarcinoma (COAD) is one of the most common malignancies and angiogenesis is vital to the development of cancer. Here, we explored the roles of angiogenesis-related genes (ARGs) that affect the prognosis of COAD and constructed risk models to assess patient prognosis, immune characteristics, and treatment outcomes.MethodsWe comprehensively characterized the transcriptional and genetic modifications of 48 ARGs in COAD and evaluated the expression patterns. We identified two ARG subgroups using the consensus clustering algorithm. Based on the differentially expressed genes (DEGs) of two ARG subtypes, we calculated risk score, namely ARG_scores, and calssified COAD patients into different risk groups. To investigate the expression of ARG_score-related genes, qRT-PCR was performed. Subsequently, we mapped the nomogram to visually and accurately describe the value of the application of ARG_score. Finally, the correlation between ARG_score and clinical features, immune infiltration along with drug sensitivity were explored.ResultsWe identified two ARG related subgroups and there were great differences in overall survival (OS) and tumor microenvironment. Then, we created an ARG_score for predicting overall survival based on eight DEGs and confirmed its reliable predictive power in COAD patients, with higher ARG_score associated with worse prognosis. Furthermore, eight ARG_score-related genes expression was investigated by qRT-PCR. To make the ARG_score clinically feasible, we created a highly reliable nomogram. We also found a higher proportion of microsatellite instability-high (MSI-H) and higher tumor mutational burden (TMB) in the high-risk group. In addition, ARG_score was notably correlated with cancer stem cell indices and drug sensitivity.ConclusionThis scoring model has potential clinical application value in the prognosis, immune microenvironment and therapeutic drug sensitivity of COAD, which provides new insights for personalized treatment.

Project description:BackgroundCuproptosis is a novel form of cellular demise that occurs through a unique pathway involving lipoylated proteins in the tricarboxylic acid (TCA) cycle and is closely linked to mitochondrial metabolism. Nevertheless, the comprehensive elucidation of the impact of carcinogenesis-associated genes (CRGs) on prognosis, tumor microenvironment (TME), and therapeutic response in patients with gastric cancer (GC) remains unclear.MethodsIn total, 1374 GC samples were gathered from three Gene Expression Omnibus (GEO) datasets and The Cancer Genome Atlas database. The samples were then stratified into different subtypes through unsupervised clustering of the 13 CRG profiles. The CRG_score was developed to quantify CRG patterns of individual tumors. Subsequently, we investigated the associations among the various groups and clinicopathological features, immune infiltration features, TME mutation status, and response to immunotherapy.ResultsThe GC samples were divided into two clusters based on their distinct clinicopathological features, prognosis, and immune characteristics. Using LASSO and Cox regression analyses, 9 genes were identified for constructing a prognostic signature related to cuproptosis. The novel signature displayed outstanding durability and prognostic capability for the overall lifespan of individuals. Additionally, the expression levels of signature genes in GC tissues and adjacent normal tissues were tested by qRT-PCR. Moreover, we developed a remarkably dependable nomogram to enhance the practicality of the CRG_score in clinical settings. High tumor mutation burden, increased microsatellite instability-high, immune activation, along with good survival probability and increased immunoreactivity to immune checkpoint inhibitors, were distinguishing features of low CRG_scores.ConclusionsThe findings of this study revealed the possible impacts of CRGs on the TME, clinical and pathological characteristics, and outlook of patients with GC. This signature was strongly linked to the immune response against GC and has the potential to serve as a valuable tool for predicting patient prognosis.

Project description:BackgroundBladder cancer (BLCA) is the most common malignancy of the urinary tract. On the other hand, disulfidptosis, a mechanism of disulfide stress-induced cell death, is closely associated with tumorigenesis and progression. Here, we investigated the impact of disulfidptosis-related genes (DRGs) on the prognosis of BLCA, identified various DRG clusters, and developed a risk model to assess patient prognosis, immunological profile, and treatment response.MethodsThe expression and mutational characteristics of four DRGs were first analyzed in bulk RNA-Seq and single-cell RNA sequencing data, IHC staining identified the role of DRGs in BLCA progression, and two DRG clusters were identified by consensus clustering. Using the differentially expressed genes (DEGs) from these two clusters, we transformed ten machine learning algorithms into more than 80 combinations and finally selected the best algorithm to construct a disulfidptosis-related prognostic signature (DRPS). We based this selection on the mean C-index of three BLCA cohorts. Furthermore, we explored the differences in clinical characteristics, mutational landscape, immune cell infiltration, and predicted efficacy of immunotherapy between high and low-risk groups. To visually depict the clinical value of DRPS, we employed nomograms. Additionally, we verified whether DRPS predicts response to immunotherapy in BLCA patients by utilizing the Tumour Immune Dysfunction and Rejection (TIDE) and IMvigor 210 cohorts.ResultsIn the integrated cohort, we identified several DRG clusters and DRG gene clusters that differed significantly in overall survival (OS) and tumor microenvironment. After the integration of clinicopathological features, DRPS showed robust predictive power. Based on the median risk score associated with disulfidptosis, BLCA patients were divided into low-risk (LR) and high-risk (HR) groups, with patients in the LR group having a better prognosis, a higher tumor mutational load and being more sensitive to immunotherapy and chemotherapy.ConclusionOur study, therefore, provides a valuable tool to further guide clinical management and tailor the treatment of BLCA patients, offering new insights into individualized treatment.

Project description:BackgroundFour RNA adenosine modifications, including m6A, m1A, alternative polyadenylation, and adenosine-to-inosine RNA editing, have been identified as potentially valuable in influencing colorectal carcinogenesis, immune infiltration, and response to drug therapy. However, the regulatory mechanisms and clinical significance of these four RNA modifications in ovarian cancer (OC) remain unknown.MethodsWe comprehensively described the transcriptional and genetic modifications of 26 RNA modification "writers" in OC and assessed the expression patterns. We identified two RNA modification subtypes using an unsupervised clustering approach. Subsequently, using differentially expressed genes (DEGs) in both subtypes, we calculated RNA modification "writer" scores (RMW scores) to characterize the RNA modifications of single OC patients. RMW score-related gene expression was investigated by qRT-PCR. We explored the correlation between RMW score and clinical features, immune infiltration, and drug sensitivity. We drew a nomogram to more intuitively and accurately describe the application value of the RMW score.ResultsWe found that molecular alterations in "writers" are strongly related to prognostic and immune-infiltrating features in OC patients. We identified two different clusters of RNA modifications. According to the immune infiltration characteristics in the two RNA modification isoforms, cluster A and cluster B can correspond to "hot" and "cold" tumors, respectively. With the median RMW score, we classified the patients into high- and low-score subgroups. A low RMW score was associated with good patient prognosis and lower immune infiltration. In addition, a low RMW score equated with a higher cancer stem cell index and a lower tumor mutation burden, which to some extent affected the sensitivity of patients to therapeutic drugs. Seven RMW score-related gene expressions were investigated by qRT-PCR in three OC cell lines. Compared to previously known models, our established RMW score has higher accuracy in predicting patient survival.ConclusionA comprehensive analysis of four RNA modification patterns in OC reveals their potential value in OC prognosis, immune microenvironment, and drug sensitivity. These results could deepen our knowledge of RNA modification and yield fresh insights for new personalized therapeutic strategies.

Project description:BackgroundPancreatic adenocarcinoma (PDAC) is a malignant tumor with high heterogeneity and poor prognosis. In this study, we sought to identify the value of platelet-related genes in prognosis and heterogeneity of PDAC through multiple transcriptomic methods.MethodsBased on datasets from Gene Expression Omnibus and The Cancer Genome Atlas (TCGA), platelet-related genes were screened out, and the TCGA cohort (n = 171) was identified into two subtypes by unsupervised clustering. The platelet-related risk score model (PLRScore) was constructed by univariate Cox and LASSO regression, and the predictive ability was evaluated by Kaplan-Meier test and time-dependent receiver operating characteristic (ROC) curves. The results were validated in two other external validation sets, ICGC-CA (n = 140) and GSE62452 (n = 66). Furthermore, predictive nomogram containing clinical characteristics and PLRScore was established. In addition, we determined the possible correlation between PLRScore and immune infiltration and response of immunotherapy. Finally, we analyzed the heterogeneity of our signature in various types of cells using single-cell analysis.ResultsPlatelet-related subtypes that have significant difference of overall survival and immune states (p < 0.05) were identified. PLRScore model based on four-gene signature (CEP55, LAMA3, CA12, SCN8A) was constructed to predict patient prognosis. The AUCs of training cohort were 0.697, 0.687 and 0.675 for 1-, 3-and 5-year, respectively. Further evaluation of the validation cohorts yielded similar results. In addition, PLRScore was associated with immune cell infiltration and immune checkpoint expression, and had promising ability to predict response to immunotherapy of PDAC.ConclusionsIn this study, the platelet-related subtypes were identified and the four-gene signature was constructed and validated. It may provide new insights into the therapeutic decision-making and molecular targets of PDAC.

Project description:ObjectiveTo establish a prognostic signature for lung adenocarcinoma (LUAD) based on cuproptosis-related long non-coding RNAs (lncRNAs), and to study the immune-related functions of LUAD.MethodsFirst, transcriptome data and clinical data related to LUAD were downloaded from the Cancer Genome Atlas (TCGA), and cuproptosis-related genes were analyzed to identify cuproptosis-related lncRNAs. Univariate COX analysis, least absolute shrinkage and selection operator (LASSO) analysis, and multivariate COX analysis were performed to analyze the cuproptosis-related lncRNAs, and a prognostic signature was established. Second, univariate COX analysis and multivariate COX analysis were performed for independent prognostic analyses. Receiver operating characteristic (ROC) curves, C index, survival curve, nomogram, and principal component analysis (PCA) were performed to evaluate the results of the independent prognostic analyses. Finally, gene enrichment analyses and immune-related function analyses were also carried out.Results(1) A total of 1,297 cuproptosis-related lncRNAs were screened. (2) A LUAD prognostic signature containing 13 cuproptosis-related lncRNAs was constructed (NIFK-AS1, AC026355.2, SEPSECS-AS1, AL360270.1, AC010999.2, ABCA9-AS1, AC032011.1, AL162632.3, LINC02518, LINC0059, AL031600.2, AP000346.1, AC012409.4). (3) The area under the multi-indicator ROC curves at 1, 3, and 5 years were AUC1 = 0.742, AUC2 = 0.708, and AUC3 = 0.762, respectively. The risk score of the prognostic signature could be used as an independent prognostic factor that was independent of other clinical indicators. (4) The results of gene enrichment analyses showed that 13 biomarkers were primarily related to amoebiasis, the wnt signaling pathway, hematopoietic cell lineage. The ssGSEA volcano map showed significant differences between high- and low-risk groups in immune-related functions, such as human leukocyte antigen (HLA), Type_II_IFN_Reponse, MHC_class_I, and Parainflammation (P < 0.001).ConclusionsThirteen cuproptosis-related lncRNAs may be clinical molecular biomarkers for the prognosis of LUAD.

Dataset Information

Crosstalk of Oxidative Phosphorylation-Related Subtypes, Establishment of a Prognostic Signature and Immune Infiltration Characteristics in Colorectal Adenocarcinoma.

Publications

Crosstalk of Oxidative Phosphorylation-Related Subtypes, Establishment of a Prognostic Signature and Immune Infiltration Characteristics in Colorectal Adenocarcinoma.

Similar Datasets

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