Dataset Information

A Recurrence-Specific Gene-Based Prognosis Prediction Model for Lung Adenocarcinoma through Machine Learning Algorithm.

ABSTRACT: Background:After curative surgical resection, about 30-75% lung adenocarcinoma (LUAD) patients suffer from recurrence with dismal survival outcomes. Identification of patients with high risk of recurrence to impose intense therapy is urgently needed. Materials and Methods:Gene expression data of LUAD were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Differentially expressed genes (DEGs) were calculated by comparing the recurrent and primary tissues. Prognostic genes associated with the recurrence-free survival (RFS) of LUAD patients were identified using univariate analysis. LASSO Cox regression and multivariate Cox analysis were applied to extract key genes and establish the prediction model. Results:We detected 37 DEGs between primary and recurrent LUAD tumors. Using univariate analysis, 31 DEGs were found to be significantly associated with RFS. We established the RFS prediction model including thirteen genes using the LASSO Cox regression. In the training cohort, we classified patients into high- and low-risk groups and found that patients in the high-risk group suffered from worse RFS compared to those in the low-risk group (P < 0.01). Concordant results were confirmed in the internal and external validation cohort. The efficiency of the prediction model was also confirmed under different clinical subgroups. The high-risk group was significantly identified as the risk factor of recurrence in LUAD by the multivariate Cox analysis (HR = 13.37, P = 0.01). Compared to clinicopathological features, our prediction model possessed higher accuracy to identify patients with high risk of recurrence (AUC = 96.3%). Finally, we found that the G2M checkpoint pathway was enriched both in recurrent tumors and primary tumors of high-risk patients. Conclusions:Our recurrence-specific gene-based prognostic prediction model provides extra information about the risk of recurrence in LUAD, which is conducive for clinicians to conduct individualized therapy in clinic.

SUBMITTER: Xu S

PROVIDER: S-EPMC7669350 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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A Recurrence-Specific Gene-Based Prognosis Prediction Model for Lung Adenocarcinoma through Machine Learning Algorithm.

Xu Shaohua S Zhou Jie J Liu Kai K Chen Zhoumiao Z He Zhengfu Z

BioMed research international 20201107

<h4>Background</h4>After curative surgical resection, about 30-75% lung adenocarcinoma (LUAD) patients suffer from recurrence with dismal survival outcomes. Identification of patients with high risk of recurrence to impose intense therapy is urgently needed.<h4>Materials and methods</h4>Gene expression data of LUAD were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Differentially expressed genes (DEGs) were calculated by comparing the recurrent and pri ...[more]

PMID: 33224985

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Project description:Accurate prognostic prediction is crucial for treatment decision-making in lung papillary adenocarcinoma (LPADC). The aim of this study was to predict cancer-specific survival in LPADC using ensemble machine learning and classical Cox regression models. Moreover, models were evaluated to provide recommendations based on quantitative data for personalized treatment of LPADC. Data of patients diagnosed with LPADC (2004-2018) were extracted from the Surveillance, Epidemiology, and End Results database. The set of samples was randomly divided into the training and validation sets at a ratio of 7:3. Three ensemble models were selected, namely gradient boosting survival (GBS), random survival forest (RSF), and extra survival trees (EST). In addition, Cox proportional hazards (CoxPH) regression was used to construct the prognostic models. The Harrell's concordance index (C-index), integrated Brier score (IBS), and area under the time-dependent receiver operating characteristic curve (time-dependent AUC) were used to evaluate the performance of the predictive models. A user-friendly web access panel was provided to easily evaluate the model for the prediction of survival and treatment recommendations. A total of 3615 patients were randomly divided into the training and validation cohorts (n = 2530 and 1085, respectively). The extra survival trees, RSF, GBS, and CoxPH models showed good discriminative ability and calibration in both the training and validation cohorts (mean of time-dependent AUC: > 0.84 and > 0.82; C-index: > 0.79 and > 0.77; IBS: < 0.16 and < 0.17, respectively). The RSF and GBS models were more consistent than the CoxPH model in predicting long-term survival. We implemented the developed models as web applications for deployment into clinical practice (accessible through https://shinyshine-820-lpaprediction-model-z3ubbu.streamlit.app/ ). All four prognostic models showed good discriminative ability and calibration. The RSF and GBS models exhibited the highest effectiveness among all models in predicting the long-term cancer-specific survival of patients with LPADC. This approach may facilitate the development of personalized treatment plans and prediction of prognosis for LPADC.

Project description:BackgroundOver the past few years, research into the pathogenesis of colon cancer has progressed rapidly, and cuproptosis is an emerging mode of cellular apoptosis. Exploring the relationship between colon cancer and cuproptosis benefits in identifying novel biomarkers and even improving the outcome of the disease.AimTo look at the prognostic relationship between colon cancer and the genes associated with cuproptosis and the immune system in patients. The main purpose was to assess whether reasonable induction of these biomarkers reduces mortality among patients with colon cancers.MethodData obtained from The Cancer Genome Atlas and Gene Expression Omnibus and the Genotype-Tissue Expression were used in differential analysis to explore differential expression genes associated with cuproptosis and immune activation. The least absolute shrinkage and selection operator and Cox regression algorithm was applied to build a cuproptosis- and immune-related combination model, and the model was utilized for principal component analysis and survival analysis to observe the survival and prognosis of the patients. A series of statistically meaningful transcriptional analysis results demonstrated an intrinsic relationship between cuproptosis and the micro-environment of colon cancer.ResultsOnce prognostic characteristics were obtained, the CDKN2A and DLAT genes related to cuproptosis were strongly linked to colon cancer: The first was a risk factor, whereas the second was a protective factor. The finding of the validation analysis showed that the comprehensive model associated with cuproptosis and immunity was statistically significant. Within the component expressions, the expressions of HSPA1A, CDKN2A, and UCN3 differed markedly. Transcription analysis primarily reflects the differential activation of related immune cells and pathways. Furthermore, genes linked to immune checkpoint inhibitors were expressed differently between the subgroups, which may reveal the mechanism of worse prognosis and the different sensitivities of chemotherapy.ConclusionThe prognosis of the high-risk group evaluated in the combined model was poorer, and cuproptosis was highly correlated with the prognosis of colon cancer. It is possible that we may be able to improve patients' prognosis by regulating the gene expression to intervene the risk score.

Dataset Information

A Recurrence-Specific Gene-Based Prognosis Prediction Model for Lung Adenocarcinoma through Machine Learning Algorithm.

Publications

A Recurrence-Specific Gene-Based Prognosis Prediction Model for Lung Adenocarcinoma through Machine Learning Algorithm.

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