Pan-cancer evaluation of gene expression and somatic alteration data for cancer prognosis prediction.

BACKGROUND: Over the past decades, approaches for diagnosing and treating cancer have seen significant improvement. However, the variability of patient and tumor characteristics has limited progress on methods for prognosis prediction. The development of high-throughput omics technologies now provides multiple approaches for characterizing tumors. Although a large number of published studies have focused on integration of multi-omics data and use of pathway-level models for cancer prognosis prediction, there still exists a gap of knowledge regarding the prognostic landscape across multi-omics data for multiple cancer types using both gene-level and pathway-level predictors. METHODS: In this study, we systematically evaluated three often available types of omics data (gene expression, copy number variation and somatic point mutation) covering both DNA-level and RNA-level features. We evaluated the landscape of predictive performance of these three omics modalities for 33 cancer types in the TCGA using a Lasso or Group Lasso-penalized Cox model and either gene or pathway level predictors. RESULTS: We constructed the prognostic landscape using three types of omics data for 33 cancer types on both the gene and pathway levels. Based on this landscape, we found that predictive performance is cancer type dependent and we also highlighted the cancer types and omics modalities that support the most accurate prognostic models. In general, models estimated on gene expression data provide the best predictive performance on either gene or pathway level and adding copy number variation or somatic point mutation data to gene expression data does not improve predictive performance, with some exceptional cohorts including low grade glioma and thyroid cancer. In general, pathway-level models have better interpretative performance, higher stability and smaller model size across multiple cancer types and omics data types relative to gene-level models. CONCLUSIONS: Based on this landscape and comprehensively comparison, models estimated on gene expression data provide the best predictive performance on either gene or pathway level. Pathway-level models have better interpretative performance, higher stability and smaller model size relative to gene-level models.

Comparison of pathway and gene-level models for cancer prognosis prediction.

BACKGROUND: Cancer prognosis prediction is valuable for patients and clinicians because it allows them to appropriately manage care. A promising direction for improving the performance and interpretation of expression-based predictive models involves the aggregation of gene-level data into biological pathways. While many studies have used pathway-level predictors for cancer survival analysis, a comprehensive comparison of pathway-level and gene-level prognostic models has not been performed. To address this gap, we characterized the performance of penalized Cox proportional hazard models built using either pathway- or gene-level predictors for the cancers profiled in The Cancer Genome Atlas (TCGA) and pathways from the Molecular Signatures Database (MSigDB). RESULTS: When analyzing TCGA data, we found that pathway-level models are more parsimonious, more robust, more computationally efficient and easier to interpret than gene-level models with similar predictive performance. For example, both pathway-level and gene-level models have an average Cox concordance index of ~ 0.85 for the TCGA glioma cohort, however, the gene-level model has twice as many predictors on average, the predictor composition is less stable across cross-validation folds and estimation takes 40 times as long as compared to the pathway-level model. When the complex correlation structure of the data is broken by permutation, the pathway-level model has greater predictive performance while still retaining superior interpretative power, robustness, parsimony and computational efficiency relative to the gene-level models. For example, the average concordance index of the pathway-level model increases to 0.88 while the gene-level model falls to 0.56 for the TCGA glioma cohort using survival times simulated from uncorrelated gene expression data. CONCLUSION: The results of this study show that when the correlations among gene expression values are low, pathway-level analyses can yield better predictive performance, greater interpretative power, more robust models and less computational cost relative to a gene-level model. When correlations among genes are high, a pathway-level analysis provides equivalent predictive power compared to a gene-level analysis while retaining the advantages of interpretability, robustness and computational efficiency.

Uncovering the prognostic gene signatures for the improvement of risk stratification in cancers by using deep learning algorithm coupled with wavelet transform.

BACKGROUND: The aim of gene expression-based clinical modelling in tumorigenesis is not only to accurately predict the clinical endpoints, but also to reveal the genome characteristics for downstream analysis for the purpose of understanding the mechanisms of cancers. Most of the conventional machine learning methods involved a gene filtering step, in which tens of thousands of genes were firstly filtered based on the gene expression levels by a statistical method with an arbitrary cutoff. Although gene filtering procedure helps to reduce the feature dimension and avoid overfitting, there is a risk that some pathogenic genes important to the disease will be ignored. RESULTS: In this study, we proposed a novel deep learning approach by combining a convolutional neural network with stationary wavelet transform (SWT-CNN) for stratifying cancer patients and predicting their clinical outcomes without gene filtering based on tumor genomic profiles. The proposed SWT-CNN overperformed the state-of-art algorithms, including support vector machine (SVM) and logistic regression (LR), and produced comparable prediction performance to random forest (RF). Furthermore, for all the cancer types, we firstly proposed a method to weight the genes with the scores, which took advantage of the representative features in the hidden layer of convolutional neural network, and then selected the prognostic genes for the Cox proportional-hazards regression. The results showed that risk stratifications can be effectively improved by using the identified prognostic genes as feature, indicating that the representative features generated by SWT-CNN can well correlate the genes with prognostic risk in cancers and be helpful for selecting the prognostic gene signatures. CONCLUSIONS: Our results indicated that gene expression-based SWT-CNN model can be an excellent tool for stratifying the prognostic risk for cancer patients. In addition, the representative features of SWT-CNN were validated to be useful for evaluating the importance of the genes in the risk stratification and can be further used to identify the prognostic gene signatures.

Multi-omics facilitated variable selection in Cox-regression model for cancer prognosis prediction.

MOTIVATION: New developments in high-throughput genomic technologies have enabled the measurement of diverse types of omics biomarkers in a cost-efficient and clinically-feasible manner. Developing computational methods and tools for analysis and translation of such genomic data into clinically-relevant information is an ongoing and active area of investigation. For example, several studies have utilized an unsupervised learning framework to cluster patients by integrating omics data. Despite such recent advances, predicting cancer prognosis using integrated omics biomarkers remains a challenge. There is also a shortage of computational tools for predicting cancer prognosis by using supervised learning methods. The current standard approach is to fit a Cox regression model by concatenating the different types of omics data in a linear manner, while penalty could be added for feature selection. A more powerful approach, however, would be to incorporate data by considering relationships among omics datatypes. METHODS: Here we developed two methods: a SKI-Cox method and a wLASSO-Cox method to incorporate the association among different types of omics data. Both methods fit the Cox proportional hazards model and predict a risk score based on mRNA expression profiles. SKI-Cox borrows the information generated by these additional types of omics data to guide variable selection, while wLASSO-Cox incorporates this information as a penalty factor during model fitting. RESULTS: We show that SKI-Cox and wLASSO-Cox models select more true variables than a LASSO-Cox model in simulation studies. We assess the performance of SKI-Cox and wLASSO-Cox using TCGA glioblastoma multiforme and lung adenocarcinoma data. In each case, mRNA expression, methylation, and copy number variation data are integrated to predict the overall survival time of cancer patients. Our methods achieve better performance in predicting patients' survival in glioblastoma and lung adenocarcinoma.

Applying a computer-aided scheme to detect a new radiographic image marker for prediction of chemotherapy outcome.

BACKGROUND: To investigate the feasibility of automated segmentation of visceral and subcutaneous fat areas from computed tomography (CT) images of ovarian cancer patients and applying the computed adiposity-related image features to predict chemotherapy outcome. METHODS: A computerized image processing scheme was developed to segment visceral and subcutaneous fat areas, and compute adiposity-related image features. Then, logistic regression models were applied to analyze association between the scheme-generated assessment scores and progression-free survival (PFS) of patients using a leave-one-case-out cross-validation method and a dataset involving 32 patients. RESULTS: The correlation coefficients between automated and radiologist's manual segmentation of visceral and subcutaneous fat areas were 0.76 and 0.89, respectively. The scheme-generated prediction scores using adiposity-related radiographic image features significantly associated with patients' PFS (p < 0.01). CONCLUSION: Using a computerized scheme enables to more efficiently and robustly segment visceral and subcutaneous fat areas. The computed adiposity-related image features also have potential to improve accuracy in predicting chemotherapy outcome.

An ensemble-based serial cascaded attention network and improved variational auto encoder for breast cancer prognosis prediction using data.

Breast cancer is one of the most common types of cancer in women and it produces a huge amount of death rate in the world. Early recognition is lessening its impact. The early recognition of breast cancer could convince patients to receive surgical therapy, which will significantly improve the chance of restoration. This information is used by the machine learning technique to find links between them and appraise our forecasts of fresh occurrences. Later recognition of breast cancer can lead to death. An accurate prescient framework for breast cancer prediction is urgently needed in the current era. In order to accomplish the objective, an adaptive ensemble model is proposed for breast cancer prognosis prediction using data. At the initial stage, the raw data are fetched from benchmark datasets. It is then followed by data cleaning and preprocessing. Subsequently, the pre-processed data is fed into the Improved Variational Autoencoder (IVAE), where the deep features are extracted. Finally, the resultant features are given as input to the Ensemble-based Serial Cascaded Attention Network (ESCANet), which is built with Deep Temporal Convolution Network (DTCN), Bi-directional Long Short-Term Memory (BiLSTM), and Recurrent Neural Network (RNN). The effectiveness of the model is validated and compared with conventional methodologies. Therefore, the results elucidate that the proposed methodology achieves extensive results; thus, it increases the system's efficiency.

A prognostic prediction model for ovarian cancer using a cross-modal view correlation discovery network.

Ovarian cancer is a tumor with different clinicopathological and molecular features, and the vast majority of patients have local or extensive spread at the time of diagnosis. Early diagnosis and prognostic prediction of patients can contribute to the understanding of the underlying pathogenesis of ovarian cancer and the improvement of therapeutic outcomes. The occurrence of ovarian cancer is influenced by multiple complex mechanisms, including the genome, transcriptome and proteome. Different types of omics analysis help predict the survival rate of ovarian cancer patients. Multi-omics data of ovarian cancer exhibit high-dimensional heterogeneity, and existing methods for integrating multi-omics data have not taken into account the variability and inter-correlation between different omics data. In this paper, we propose a deep learning model, MDCADON, which utilizes multi-omics data and cross-modal view correlation discovery network. We introduce random forest into LASSO regression for feature selection on mRNA expression, DNA methylation, miRNA expression and copy number variation (CNV), aiming to select important features highly correlated with ovarian cancer prognosis. A multi-modal deep neural network is used to comprehensively learn feature representations of each omics data and clinical data, and cross-modal view correlation discovery network is employed to construct the multi-omics discovery tensor, exploring the inter-relationships between different omics data. The experimental results demonstrate that MDCADON is superior to the existing methods in predicting ovarian cancer prognosis, which enables survival analysis for patients and facilitates the determination of follow-up treatment plans. Finally, we perform Gene Ontology (GO) term analysis and biological pathway analysis on the genes identified by MDCADON, revealing the underlying mechanisms of ovarian cancer and providing certain support for guiding ovarian cancer treatments.

Application of Deep Learning in Cancer Prognosis Prediction Model.

As an important branch of artificial intelligence and machine learning, deep learning (DL) has been widely used in various aspects of cancer auxiliary diagnosis, among which cancer prognosis is the most important part. High-accuracy cancer prognosis is beneficial to the clinical management of patients with cancer. Compared with other methods, DL models can significantly improve the accuracy of prediction. Therefore, this article is a systematic review of the latest research on DL in cancer prognosis prediction. First, the data type, construction process, and performance evaluation index of the DL model are introduced in detail. Then, the current mainstream baseline DL cancer prognosis prediction models, namely, deep neural networks, convolutional neural networks, deep belief networks, deep residual networks, and vision transformers, including network architectures, the latest application in cancer prognosis, and their respective characteristics, are discussed. Next, some key factors that affect the predictive performance of the model and common performance enhancement techniques are listed. Finally, the limitations of the DL cancer prognosis prediction model in clinical practice are summarized, and the future research direction is prospected. This article could provide relevant researchers with a comprehensive understanding of DL cancer prognostic models and is expected to promote the research progress of cancer prognosis prediction.

Multimodal adversarial representation learning for breast cancer prognosis prediction.

With the increasing incidence of breast cancer, accurate prognosis prediction of breast cancer patients is a key issue in current cancer research, and it is also of great significance for patients' psychological rehabilitation and assisting clinical decision-making. Many studies that integrate data from different heterogeneous modalities such as gene expression profile, clinical data, and copy number alteration, have achieved greater success than those with only one modality in prognostic prediction. However, many of these approaches that exist fail to dramatically reduce the modality gap by aligning multimodal distributions. Therefore, it is crucial to develop a method that fully considers a modality-invariant embedding space to effectively integrate multimodal data. In this study, to reduce the modality gap, we propose a multimodal data adversarial representation framework (MDAR) to reduce the modal heterogeneity by translating source modalities into distributions for the target modality. Additionally, we apply reconstruction and classification losses to embedding space to further constrain it. Then, we design a multi-scale bilinear convolutional neural network (MS-B-CNN) for uni-modality to improve the feature expression ability. In addition, the embedding space generates predictions as stacked feature inputs to the extremely randomized trees classifier. With 10-fold cross-validation, our results show that the proposed adversarial representation learning improves prognostic performance. A comparative study of this method and other existing methods on the METABRIC (1980 patients) dataset showed that Matthews correlation coefficient (Mcc) was significantly enhanced by 7.4% in the prognosis prediction of breast cancer patients.

Review of T cell proliferation regulatory factors in treatment and prognostic prediction for solid tumors.

T cell proliferation regulators (Tcprs), which are positive regulators that promote T cell function, have made great contributions to the development of therapies to improve T cell function. CAR (chimeric antigen receptor) -T cell therapy, a type of adoptive cell transfer therapy that targets tumor cells and enhances immune lethality, has led to significant progress in the treatment of hematologic tumors. However, the applications of CAR-T in solid tumor treatment remain limited. Therefore, in this review, we focus on the development of Tcprs for solid tumor therapy and prognostic prediction. We summarize potential strategies for targeting different Tcprs to enhance T cell proliferation and activation and inhibition of cancer progression, thereby improving the antitumor activity and persistence of CAR-T. In summary, we propose means of enhancing CAR-T cells by expressing different Tcprs, which may lead to the development of a new generation of cell therapies.

Developing global image feature analysis models to predict cancer risk and prognosis.

In order to develop precision or personalized medicine, identifying new quantitative imaging markers and building machine learning models to predict cancer risk and prognosis has been attracting broad research interest recently. Most of these research approaches use the similar concepts of the conventional computer-aided detection schemes of medical images, which include steps in detecting and segmenting suspicious regions or tumors, followed by training machine learning models based on the fusion of multiple image features computed from the segmented regions or tumors. However, due to the heterogeneity and boundary fuzziness of the suspicious regions or tumors, segmenting subtle regions is often difficult and unreliable. Additionally, ignoring global and/or background parenchymal tissue characteristics may also be a limitation of the conventional approaches. In our recent studies, we investigated the feasibility of developing new computer-aided schemes implemented with the machine learning models that are trained by global image features to predict cancer risk and prognosis. We trained and tested several models using images obtained from full-field digital mammography, magnetic resonance imaging, and computed tomography of breast, lung, and ovarian cancers. Study results showed that many of these new models yielded higher performance than other approaches used in current clinical practice. Furthermore, the computed global image features also contain complementary information from the features computed from the segmented regions or tumors in predicting cancer prognosis. Therefore, the global image features can be used alone to develop new case-based prediction models or can be added to current tumor-based models to increase their discriminatory power.

Predicting cancer prognosis using functional genomics data sets.

Elucidating the molecular basis of human cancers is an extremely complex and challenging task. A wide variety of computational tools and experimental techniques have been used to address different aspects of this characterization. One major hurdle faced by both clinicians and researchers has been to pinpoint the mechanistic basis underlying a wide range of prognostic outcomes for the same type of cancer. Here, we provide an overview of various computational methods that have leveraged different functional genomics data sets to identify molecular signatures that can be used to predict prognostic outcome for various human cancers. Furthermore, we outline challenges that remain and future directions that may be explored to address them.