Cancer Informatics最新文献

The aim of this study was to utilize a computational methodology based on Gene Reversal Rate (GRR) scoring to repurpose existing drugs for a rare and understudied cancer: inflammatory breast cancer (IBC). This method uses IBC-related gene expression signatures (GES) and drug-induced gene expression profiles from the LINCS database to calculate a GRR score for each candidate drug, and is based on the idea that a compound that can counteract gene expression changes of a disease may have potential therapeutic applications for that disease. Genes related to IBC with associated differential expression data (265 up-regulated and 122 down-regulated) were collated from PubMed-indexed publications. Drug-induced gene expression profiles were downloaded from the LINCS database and candidate drugs to treat IBC were predicted using their GRR scores. Thirty-two (32) drug perturbations that could potentially reverse the pre-compiled list of 297 IBC genes were obtained using the LINCS Canvas Browser (LCB) analysis. Binary combinations of the 32 perturbations were assessed computationally to identify combined perturbations with the highest GRR scores, and resulted in 131 combinations with GRR greater than 80%, that reverse up to 264 of the 297 genes in the IBC-GES. The top 35 combinations involve 20 unique individual drug perturbations, and 19 potential drug candidates. A comprehensive literature search confirmed 17 of the 19 known drugs as having either anti-cancer or anti-inflammatory activities. AZD-7545, BMS-754807, and nimesulide target known IBC relevant genes: PDK, Met, and COX, respectively. AG-14361, butalbital, and clobenpropit are known to be functionally relevant in DNA damage, cell cycle, and apoptosis, respectively. These findings support the use of the GRR approach to identify drug candidates and potential combination therapies that could be used to treat rare diseases such as IBC.

[This corrects the article DOI: 10.1177/11769351231154186.].

Background: In recent years, interest in prognostic calculators for predicting patient health outcomes has grown with the popularity of personalized medicine. These calculators, which can inform treatment decisions, employ many different methods, each of which has advantages and disadvantages.

Methods: We present a comparison of a multistate model (MSM) and a random survival forest (RSF) through a case study of prognostic predictions for patients with oropharyngeal squamous cell carcinoma. The MSM is highly structured and takes into account some aspects of the clinical context and knowledge about oropharyngeal cancer, while the RSF can be thought of as a black-box non-parametric approach. Key in this comparison are the high rate of missing values within these data and the different approaches used by the MSM and RSF to handle missingness.

Results: We compare the accuracy (discrimination and calibration) of survival probabilities predicted by both approaches and use simulation studies to better understand how predictive accuracy is influenced by the approach to (1) handling missing data and (2) modeling structural/disease progression information present in the data. We conclude that both approaches have similar predictive accuracy, with a slight advantage going to the MSM.

Conclusions: Although the MSM shows slightly better predictive ability than the RSF, consideration of other differences are key when selecting the best approach for addressing a specific research question. These key differences include the methods' ability to incorporate domain knowledge, and their ability to handle missing data as well as their interpretability, and ease of implementation. Ultimately, selecting the statistical method that has the most potential to aid in clinical decisions requires thoughtful consideration of the specific goals.

This review discusses the possible involvement of infections-associated cancers in humans, with virus infections contributing 15% to 20% of total cancer cases in humans. DNA virus encoded proteins interact with host cellular signaling pathways and control proliferation, cell death and genomic integrity viral oncoproteins are known to bind cellular Deubiquitinates (DUBs) such as cyclindromatosis tumor suppressor, ubiquitin-specific proteases 7, 11, 15 and 20, and A-20 to improve their intracellular stability and cellular signaling pathways and finally transformation. Human papillomaviruses (cervical carcinoma, oral cancer and laryngeal cancer); human polyomaviruses (mesotheliomas, brain tumors); Epstein-Barr virus (B-cell lymphoproliferative diseases and nasopharyngeal carcinoma); Kaposi's Sarcoma Herpesvirus (Kaposi's Sarcoma and primary effusion lymphomas); hepatitis B (hepatocellular carcinoma (HCC)) cause up to 20% of malignancies around the world.

The relevance of nongenetic factors to prostate cancer (PCa) has been elusive. We aimed to quantify the contributions of environmental factors to PCa and identify risk-related diet metrics and relevant racial disparities. We performed a unique analysis of the Diet History Questionnaire data of 41 830 European Americans (EAs) and 1282 African Americans (AAs) in the PLCO project. The independent variables in the regression models consisted of age at trial entry, race, family history of prostate cancer (PCa-fh), diabetes history, body mass index (BMI), lifestyle (smoking and coffee consumption), marital status, and a specific nutrient/food factor (X). P < .05 and a 95% confidence interval excluding zero were adopted as the criteria for determining a significant difference (effect). We established a priority ranking among PCa risk-related genetic and environmental factors according to the deviances explained by them in the multivariate Cox-PH regression analysis: age > PCa-fh > diabetes ⩾ race > lifestyle ⩾marital-status ⩾BMI > X. We confirmed previous studies showing that (1) high protein and saturated fat levels in diet were related to increased PCa risk, (2) high-level supplementary selenium intake was harmful rather than beneficial for preventing PCa, and (3) supplementary vitamin B6 was beneficial for preventing benign PCa. We obtained the following novel findings: high-level organ meat intake was an independent predictor for increased aggressive PCa risk; supplementary iron, copper and magnesium increased benign PCa risk; and the AA diet was "healthy" in terms of the relatively lower protein and fat levels and was "unhealthy" in that it more commonly contained organ meat. In conclusion, we established a priority ranking among the contributing factors for PCa and identified several risk-related diet metrics and the racial disparities. Our findings suggested some new approaches to prevent PCa such as restriction of organ meat intake and supplementary microminerals.

Epidemiologic evidence for the association of cholesterol and breast cancer is inconsistent. Several factors may contribute to this inconsistency, including limited sample sizes, confounding effects of antihyperlipidemic treatment, age, and body mass index, and the assumption that the association follows a simple linear function. Here, we aimed to address these factors by combining visualization and quantification a large-scale contemporary electronic health record database (the All of Us Research Program). We find clear visual and quantitative evidence that breast cancer is strongly, positively, and near-linearly associated with total cholesterol and low-density lipoprotein cholesterol, but not associated with triglycerides. The association of breast cancer with high-density lipoprotein cholesterol was non-linear and age dependent. Standardized odds ratios were 2.12 (95% confidence interval 1.9-2.48), P = 5.6 × 10^-31 for total cholesterol; 1.99 (1.75-2.26), P = 2.6 × 10^-26 for low-density lipoprotein cholesterol; 1.69 (1.3-2.2), P = 9.0 × 10^-5 for high-density lipoprotein cholesterol at age < 56; and 0.65 (0.55-0.78), P = 1.2 × 10^-6 for high-density lipoprotein cholesterol at age ⩾ 56. The inclusion of the lipid levels measured after antihyperlipidemic treatment in the analysis results in erroneous associations. We demonstrate that the use of the logistic regression without inspecting risk variable linearity and accounting for confounding effects may lead to inconsistent results.

The second most frequent malignancy in women worldwide is cervical cancer. In the transformation(transitional) zone, which is a region of the cervix, columnar cells are continuously converting into squamous cells. The most typical location on the cervix for the development of aberrant cells is the transformation zone, a region of transforming cells. This article suggests a 2-phase method that includes segmenting and classifying the transformation zone to identify the type of cervical cancer. In the initial stage, the transformation zone is segmented from the colposcopy images. The segmented images are then subjected to the augmentation process and identified with the improved inception-resnet-v2. Here, multi-scale feature fusion framework that utilizes 3 × 3 convolution kernels from Reduction-A and Reduction-B of inception-resnet-v2 is introduced. The feature extracted from Reduction-A and Reduction -B is concatenated and fed to SVM for classification. This way, the model combines the benefits of residual networks and Inception convolution, increasing network width and resolving the deep network's training issue. The network can extract several scales of contextual information due to the multi-scale feature fusion, which increases accuracy. The experimental results reveal 81.24% accuracy, 81.24% sensitivity, 90.62% specificity, 87.52% precision, 9.38% FPR, and 81.68% F1 score, 75.27% MCC, and 57.79% Kappa coefficient.

[This corrects the article DOI: 10.1177/11769351231177267.].