Objectives: Emerging evidence suggests that N6-methyladenosine (m6A) methylation plays a critical role in cancers through various mechanisms. This work aims to reveal the essential role of m6A methylation "readers" in regulation of cancer prognosis at the pan-cancer level.
Methods: Herein, we focused on one special protein family of the "readers" of m6A methylation, YT521-B homology (YTH) domain family genes, which were observed to be frequently dysregulated in tumor tissues and closely associated with cancer prognosis. Then, a comprehensive analysis of modulation in cancer prognosis was conducted by integrating RNA sequencing (RNAseq) datasets of YTH family genes and clinical information at the pan-cancer level.
Results: YTH family genes were significantly differentially expressed in most of the cancers, particularly increased in Gastrointestinal cancers, and decreased in Endocrine and Urologic cancers. In addition, they were observed to be associated with overall survival (OS) and disease-specific survival (DSS) with various extent, especially in lower grade glioma (LGG), thyroid cancer (THCA), liver hepatocellular carcinoma (LIHC) and kidney clear cell carcinoma (KIRC), so were some "writers" (METLL3, METLL14, WTAP) and "erasers" (FTO, ALKBH5). Further survival analysis illustrated that YTH family genes specifically YTHScore constructed by combining 5 YTH family genes, as well as RWEScore calculated by combining genes from "readers"-"writers"-"erasers" could dramatically distinguish tumor prognosis in 4 representative cancers. As expected, YTHScore presented an equally comparable prognostic classification with RWEScore. Finally, analysis of immune signatures and clinical characteristics implied that, the activity of the innate immune, diagnostic age, clinical stage, Tumor-Node-Metastasis (TNM) stage and immune types, might play specific roles in modulating tumor prognosis.
Conclusions: The study demonstrated that YTH family genes had the potential to predict tumor prognosis, in which the YTHScore illustrated equal ability to predict tumor prognosis compared to RWEScore, thus providing insights into prognostic biomarkers and therapeutic targets at the pan-cancer level.
{"title":"Detecting the Tumor Prognostic Factors From the YTH Domain Family Through Integrative Pan-Cancer Analysis.","authors":"Chong-Ying Zhu, Qi-Wei Yang, Xin-Yue Mu, Yan-Yu Zhai, Wen-Yan Zhao, Zuo-Jing Yin","doi":"10.1177/11769351241300030","DOIUrl":"10.1177/11769351241300030","url":null,"abstract":"<p><strong>Objectives: </strong>Emerging evidence suggests that N6-methyladenosine (m<sup>6</sup>A) methylation plays a critical role in cancers through various mechanisms. This work aims to reveal the essential role of m<sup>6</sup>A methylation \"readers\" in regulation of cancer prognosis at the pan-cancer level.</p><p><strong>Methods: </strong>Herein, we focused on one special protein family of the \"readers\" of m<sup>6</sup>A methylation, YT521-B homology (YTH) domain family genes, which were observed to be frequently dysregulated in tumor tissues and closely associated with cancer prognosis. Then, a comprehensive analysis of modulation in cancer prognosis was conducted by integrating RNA sequencing (RNAseq) datasets of YTH family genes and clinical information at the pan-cancer level.</p><p><strong>Results: </strong>YTH family genes were significantly differentially expressed in most of the cancers, particularly increased in Gastrointestinal cancers, and decreased in Endocrine and Urologic cancers. In addition, they were observed to be associated with overall survival (OS) and disease-specific survival (DSS) with various extent, especially in lower grade glioma (LGG), thyroid cancer (THCA), liver hepatocellular carcinoma (LIHC) and kidney clear cell carcinoma (KIRC), so were some \"writers\" (METLL3, METLL14, WTAP) and \"erasers\" (FTO, ALKBH5). Further survival analysis illustrated that YTH family genes specifically YTHScore constructed by combining 5 YTH family genes, as well as RWEScore calculated by combining genes from \"readers\"-\"writers\"-\"erasers\" could dramatically distinguish tumor prognosis in 4 representative cancers. As expected, YTHScore presented an equally comparable prognostic classification with RWEScore. Finally, analysis of immune signatures and clinical characteristics implied that, the activity of the innate immune, diagnostic age, clinical stage, Tumor-Node-Metastasis (TNM) stage and immune types, might play specific roles in modulating tumor prognosis.</p><p><strong>Conclusions: </strong>The study demonstrated that YTH family genes had the potential to predict tumor prognosis, in which the YTHScore illustrated equal ability to predict tumor prognosis compared to RWEScore, thus providing insights into prognostic biomarkers and therapeutic targets at the pan-cancer level.</p>","PeriodicalId":35418,"journal":{"name":"Cancer Informatics","volume":"23 ","pages":"11769351241300030"},"PeriodicalIF":2.4,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11569503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-08eCollection Date: 2024-01-01DOI: 10.1177/11769351241297633
Monireh Shahmoradi, Ahmad Fazilat, Mostafa Ghaderi-Zefrehei, Arash Ardalan, Ali Bigdeli, Nahid Nafissi, Ebrahim Babaei, Mahsa Rahmani
Objectives: Breast cancer (BC) stands as the second-leading cause of female-specific cancer-related fatalities globally, necessitating comprehensive research to address its critical aspects. This study aimed to explore the time intervals between surgery and disease recurrence in BC patients and their survival utilizing various parametric and semi-parametric models.
Methods: After the examination of data collected from 2010 to 2021 at a BC Center in Tehran, Iran, 171 cases met the criteria for analysis out of 2246 datasets. Model fitting, was assessed through the Akaike Information Criterion (AIC), and indicated the logistic distribution as the most fit one among concurrent and independent variable models.
Results: The Cox proportional hazard regression model consistently demonstrated superior fitting, characterized by the lowest AIC values. The average age at diagnosis was 50.39 years, with a standard deviation of 11.13. Typical survival time was estimated 53.44 months, falling within a confidence interval of 51.41-55.48 months at a 95% confidence level. The 1-year survival rate was determined at 0.92 (95% CI: 0.89-0.94). Notably, patient age while cancer diagnosis, progesterone receptor (PR), tumor grade, and tumor stage were found to be statistically significant (P < .05) risk factors for prediction of BC recurrence after surgery in Iran by Cox model.
Conclusions: Our findings underscore the importance of further exploration and consideration of the identified risk factors in BC research and treatment strategies.
{"title":"Unveiling Recurrence Patterns: Analyzing Predictive Risk Factors for Breast Cancer Recurrence after Surgery.","authors":"Monireh Shahmoradi, Ahmad Fazilat, Mostafa Ghaderi-Zefrehei, Arash Ardalan, Ali Bigdeli, Nahid Nafissi, Ebrahim Babaei, Mahsa Rahmani","doi":"10.1177/11769351241297633","DOIUrl":"https://doi.org/10.1177/11769351241297633","url":null,"abstract":"<p><strong>Objectives: </strong>Breast cancer (BC) stands as the second-leading cause of female-specific cancer-related fatalities globally, necessitating comprehensive research to address its critical aspects. This study aimed to explore the time intervals between surgery and disease recurrence in BC patients and their survival utilizing various parametric and semi-parametric models.</p><p><strong>Methods: </strong>After the examination of data collected from 2010 to 2021 at a BC Center in Tehran, Iran, 171 cases met the criteria for analysis out of 2246 datasets. Model fitting, was assessed through the Akaike Information Criterion (AIC), and indicated the logistic distribution as the most fit one among concurrent and independent variable models.</p><p><strong>Results: </strong>The Cox proportional hazard regression model consistently demonstrated superior fitting, characterized by the lowest AIC values. The average age at diagnosis was 50.39 years, with a standard deviation of 11.13. Typical survival time was estimated 53.44 months, falling within a confidence interval of 51.41-55.48 months at a 95% confidence level. The 1-year survival rate was determined at 0.92 (95% CI: 0.89-0.94). Notably, patient age while cancer diagnosis, progesterone receptor (PR), tumor grade, and tumor stage were found to be statistically significant (<i>P</i> < .05) risk factors for prediction of BC recurrence after surgery in Iran by Cox model.</p><p><strong>Conclusions: </strong>Our findings underscore the importance of further exploration and consideration of the identified risk factors in BC research and treatment strategies.</p>","PeriodicalId":35418,"journal":{"name":"Cancer Informatics","volume":"23 ","pages":"11769351241297633"},"PeriodicalIF":2.4,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-21eCollection Date: 2024-01-01DOI: 10.1177/11769351241276319
Wensheng Zhang, Kun Zhang
Objectives: For prostate cancer (PCa), hundreds of risk variants have been identified. It remains unknown whether the polygenic risk score (PRS) that combines the effects of these variants is also a sufficiently informative metric with relevance to the molecular mechanisms of carcinogenesis in prostate. We aimed to understand the biological basis of PRS and racial disparities in the cancer.
Methods: We performed a comprehensive analysis of the data generated (deposited in) by several genomic and/or transcriptomic projects (databases), including the GTEx, TCGA, 1000 Genomes, GEO and dbGap. PRS was constructed from 260 PCa risk variants that were identified by a recent trans-ancestry meta-analysis and contained in the GTEx dataset. The dosages of risk variants and the multi-ancestry effects on PCa incidence estimated by the meta-analysis were used in calculating individual PRS values.
Results: The following novel results were obtained from our analyses. (1) In normal prostate samples from healthy European Americans (EAs), the expression levels of 540 genes (termed PRS genes) were associated with the PRS (P < .01). (2) Ubiquitin-proteasome system in high-PRS individuals' prostates was more active than that in low-PRS individuals' prostates. (3) Nine PRS genes play roles in the cancer progression-relevant parts, which are frequently hit by somatic mutations in PCa, of PI3K-Akt/RAS-MAPK/mTOR signaling pathways. (4) The expression profiles of the top significant PRS genes in tumor samples were capable of predicting malignant PCa relapse after prostatectomy. (5) The transcriptomic differences between African American and EA samples were incompatible with the patterns of the aforementioned associations between PRS and gene expression levels.
Conclusions: This study provided unique insights into the relationship between PRS and the molecular mechanisms of carcinogenesis in prostate. The new findings, alongside the moderate but significant heritability of PCa susceptibility contributed by the risk variants, suggest the aptness and inaptness of PRS for explaining PCa and disparities.
{"title":"Understanding the Biological Basis of Polygenic Risk Scores and Disparities in Prostate Cancer: A Comprehensive Genomic Analysis.","authors":"Wensheng Zhang, Kun Zhang","doi":"10.1177/11769351241276319","DOIUrl":"https://doi.org/10.1177/11769351241276319","url":null,"abstract":"<p><strong>Objectives: </strong>For prostate cancer (PCa), hundreds of risk variants have been identified. It remains unknown whether the polygenic risk score (PRS) that combines the effects of these variants is also a sufficiently informative metric with relevance to the molecular mechanisms of carcinogenesis in prostate. We aimed to understand the biological basis of PRS and racial disparities in the cancer.</p><p><strong>Methods: </strong>We performed a comprehensive analysis of the data generated (deposited in) by several genomic and/or transcriptomic projects (databases), including the GTEx, TCGA, 1000 Genomes, GEO and dbGap. PRS was constructed from 260 PCa risk variants that were identified by a recent trans-ancestry meta-analysis and contained in the GTEx dataset. The dosages of risk variants and the multi-ancestry effects on PCa incidence estimated by the meta-analysis were used in calculating individual PRS values.</p><p><strong>Results: </strong>The following novel results were obtained from our analyses. (1) In normal prostate samples from healthy European Americans (EAs), the expression levels of 540 genes (termed PRS genes) were associated with the PRS (<i>P</i> < .01). (2) Ubiquitin-proteasome system in high-PRS individuals' prostates was more active than that in low-PRS individuals' prostates. (3) Nine PRS genes play roles in the cancer progression-relevant parts, which are frequently hit by somatic mutations in PCa, of PI3K-Akt/RAS-MAPK/mTOR signaling pathways. (4) The expression profiles of the top significant PRS genes in tumor samples were capable of predicting malignant PCa relapse after prostatectomy. (5) The transcriptomic differences between African American and EA samples were incompatible with the patterns of the aforementioned associations between PRS and gene expression levels.</p><p><strong>Conclusions: </strong>This study provided unique insights into the relationship between PRS and the molecular mechanisms of carcinogenesis in prostate. The new findings, alongside the moderate but significant heritability of PCa susceptibility contributed by the risk variants, suggest the aptness and inaptness of PRS for explaining PCa and disparities.</p>","PeriodicalId":35418,"journal":{"name":"Cancer Informatics","volume":"23 ","pages":"11769351241276319"},"PeriodicalIF":2.4,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11497523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142509508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-16eCollection Date: 2024-01-01DOI: 10.1177/11769351241290608
Pragati Patharia, Prabira Kumar Sethy, Aziz Nanthaamornphong
Image-based diagnosis has become a crucial tool in the identification and management of various cancers, particularly lung and colon cancer. This review delves into the latest advancements and ongoing challenges in the field, with a focus on deep learning, machine learning, and image processing techniques applied to X-rays, CT scans, and histopathological images. Significant progress has been made in imaging technologies like computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET), which, when combined with machine learning and artificial intelligence (AI) methodologies, have greatly enhanced the accuracy of cancer detection and characterization. These advances have enabled early detection, more precise tumor localization, personalized treatment plans, and overall improved patient outcomes. However, despite these improvements, challenges persist. Variability in image interpretation, the lack of standardized diagnostic protocols, unequal access to advanced imaging technologies, and concerns over data privacy and security within AI-based systems remain major obstacles. Furthermore, integrating imaging data with broader clinical information is crucial to achieving a more comprehensive approach to cancer diagnosis and treatment. This review provides valuable insights into the recent developments and challenges in image-based diagnosis for lung and colon cancers, underscoring both the remarkable progress and the hurdles that still need to be overcome to optimize cancer care.
基于图像的诊断已成为识别和管理各种癌症,尤其是肺癌和结肠癌的重要工具。本综述深入探讨了该领域的最新进展和持续挑战,重点关注应用于 X 射线、CT 扫描和组织病理学图像的深度学习、机器学习和图像处理技术。计算机断层扫描(CT)、磁共振成像(MRI)和正电子发射断层扫描(PET)等成像技术取得了重大进展,这些技术与机器学习和人工智能(AI)方法相结合,大大提高了癌症检测和定性的准确性。这些进步使得早期检测、更精确的肿瘤定位、个性化治疗方案以及患者预后的全面改善成为可能。然而,尽管取得了这些进步,挑战依然存在。图像解读的不一致性、缺乏标准化的诊断方案、先进成像技术的使用机会不平等,以及对基于人工智能系统的数据隐私和安全性的担忧,仍然是主要障碍。此外,将成像数据与更广泛的临床信息相结合对于实现更全面的癌症诊断和治疗方法至关重要。本综述就基于图像的肺癌和结肠癌诊断的最新进展和挑战提供了宝贵的见解,强调了在优化癌症治疗方面取得的显著进展和仍需克服的障碍。
{"title":"Advancements and Challenges in the Image-Based Diagnosis of Lung and Colon Cancer: A Comprehensive Review.","authors":"Pragati Patharia, Prabira Kumar Sethy, Aziz Nanthaamornphong","doi":"10.1177/11769351241290608","DOIUrl":"10.1177/11769351241290608","url":null,"abstract":"<p><p>Image-based diagnosis has become a crucial tool in the identification and management of various cancers, particularly lung and colon cancer. This review delves into the latest advancements and ongoing challenges in the field, with a focus on deep learning, machine learning, and image processing techniques applied to X-rays, CT scans, and histopathological images. Significant progress has been made in imaging technologies like computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET), which, when combined with machine learning and artificial intelligence (AI) methodologies, have greatly enhanced the accuracy of cancer detection and characterization. These advances have enabled early detection, more precise tumor localization, personalized treatment plans, and overall improved patient outcomes. However, despite these improvements, challenges persist. Variability in image interpretation, the lack of standardized diagnostic protocols, unequal access to advanced imaging technologies, and concerns over data privacy and security within AI-based systems remain major obstacles. Furthermore, integrating imaging data with broader clinical information is crucial to achieving a more comprehensive approach to cancer diagnosis and treatment. This review provides valuable insights into the recent developments and challenges in image-based diagnosis for lung and colon cancers, underscoring both the remarkable progress and the hurdles that still need to be overcome to optimize cancer care.</p>","PeriodicalId":35418,"journal":{"name":"Cancer Informatics","volume":"23 ","pages":"11769351241290608"},"PeriodicalIF":2.4,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11526153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-16eCollection Date: 2024-01-01DOI: 10.1177/11769351241289719
Lujun Shen, Yiquan Jiang, Tao Zhang, Fei Cao, Liangru Ke, Chen Li, Gulijiayina Nuerhashi, Wang Li, Peihong Wu, Chaofeng Li, Qi Zeng, Weijun Fan
Objectives: Patients with intermediate or advanced hepatocellular carcinoma (HCC) require repeated disease monitoring, prognosis assessment and treatment planning. In 2018, a novel machine learning methodology "survival path" (SP) was developed to facilitate dynamic prognosis prediction and treatment planning. One year after, a deep learning approach called Dynamic Deephit was developed. The performance of the two state-of-art models in dynamic prognostication have not been compared.
Methods: We trained and tested the SP and Dynamic DeepHit models in a large cohort of 2511 HCC patients using time-series data. The time-series data were converted into data of time slices, with an interval of three months. The time-dependent c-index for OS at given prediction time (t = 1, 6, 12, 18 months) and evaluation time (∆t = 3, 6, 9, 12, 18, 24, 36, 48 months) were compared.
Results: The comparison between SP model and Dynamic DeepHit-HCC model showed the latter had significant better performance at the time of initial admission. The time-dependent c-index of Dynamic DeepHit-HCC model gradually decreased with the extension of time (from 0.756 to 0.639 in the training set; from 0.787 to 0.661 in internal testing set; from 0.725 to 0.668 in multicenter testing set); while the time-dependent c-index of SP model displayed an increased trend (from 0.665 to 0.748 in the training set; from 0.608 to 0.743 in internal testing set; from 0.643 to 0.720 in multicenter testing set). When the prediction time comes to 6 months or later since initial treatment, the survival path model outperformed the dynamic DeepHit model at late evaluation times (∆t > 12 months).
Conclusions: This research highlighted the unique strengths of both models. The SP model had advantage in long term prediction while the Dynamic DeepHit-HCC model had advantages in prediction at near time points. Fine selection of models is needed in dealing with different scenarios.
{"title":"Machine Learning for Dynamic Prognostication of Patients With Hepatocellular Carcinoma Using Time-Series Data: Survival Path Versus Dynamic-DeepHit HCC Model.","authors":"Lujun Shen, Yiquan Jiang, Tao Zhang, Fei Cao, Liangru Ke, Chen Li, Gulijiayina Nuerhashi, Wang Li, Peihong Wu, Chaofeng Li, Qi Zeng, Weijun Fan","doi":"10.1177/11769351241289719","DOIUrl":"https://doi.org/10.1177/11769351241289719","url":null,"abstract":"<p><strong>Objectives: </strong>Patients with intermediate or advanced hepatocellular carcinoma (HCC) require repeated disease monitoring, prognosis assessment and treatment planning. In 2018, a novel machine learning methodology \"survival path\" (SP) was developed to facilitate dynamic prognosis prediction and treatment planning. One year after, a deep learning approach called Dynamic Deephit was developed. The performance of the two state-of-art models in dynamic prognostication have not been compared.</p><p><strong>Methods: </strong>We trained and tested the SP and Dynamic DeepHit models in a large cohort of 2511 HCC patients using time-series data. The time-series data were converted into data of time slices, with an interval of three months. The time-dependent c-index for OS at given prediction time (<i>t</i> = 1, 6, 12, 18 months) and evaluation time (∆<i>t</i> = 3, 6, 9, 12, 18, 24, 36, 48 months) were compared.</p><p><strong>Results: </strong>The comparison between SP model and Dynamic DeepHit-HCC model showed the latter had significant better performance at the time of initial admission. The time-dependent c-index of Dynamic DeepHit-HCC model gradually decreased with the extension of time (from 0.756 to 0.639 in the training set; from 0.787 to 0.661 in internal testing set; from 0.725 to 0.668 in multicenter testing set); while the time-dependent c-index of SP model displayed an increased trend (from 0.665 to 0.748 in the training set; from 0.608 to 0.743 in internal testing set; from 0.643 to 0.720 in multicenter testing set). When the prediction time comes to 6 months or later since initial treatment, the survival path model outperformed the dynamic DeepHit model at late evaluation times (∆<i>t</i> > 12 months).</p><p><strong>Conclusions: </strong>This research highlighted the unique strengths of both models. The SP model had advantage in long term prediction while the Dynamic DeepHit-HCC model had advantages in prediction at near time points. Fine selection of models is needed in dealing with different scenarios.</p>","PeriodicalId":35418,"journal":{"name":"Cancer Informatics","volume":"23 ","pages":"11769351241289719"},"PeriodicalIF":2.4,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11483769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142476533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-14eCollection Date: 2024-01-01DOI: 10.1177/11769351241272397
Hojin Moon, Lauren Tran, Andrew Lee, Taeksoo Kwon, Minho Lee
Objectives: The primary goal of this research is to develop treatment-related genomic predictive markers for non-small cell lung cancer by integrating various machine learning algorithms that recommends near-optimal individualized patient treatment for chemotherapy in an effort to maximize efficacy or minimize treatment-related toxicity. This research can contribute toward developing a more refined, accurate and effective therapy accounting for specific patient needs.
Methods: To accomplish our research goal, we implement ensemble learning algorithms, bagging with regularized Cox regression models and nonparametric tree-based models via Random Survival Forests. A comprehensive meta-database was compiled from the NCBI Gene Expression Omnibus data repository for lung cancer patients to capture and utilize complex genomic patterns that can predict treatment outcomes more accurately.
Results: The developed novel prediction algorithm demonstrates the ability to support complex clinical decision-making processes in the treatment of NSCLC. It effectively addresses patient heterogeneity, offering predictions that are both refined and personalized in improving the precision of chemotherapy regimens prescribed to the eligible patients.
Conclusion: This research should contribute substantial advancement of cancer treatments by improving the accuracy and efficacy of chemotherapy treatments for a targeted group of patients who need the right treatment. The integration of complex machine learning techniques with genomic data holds substantial potential to transform current cancer treatment paradigms by providing robust support in clinical decision-making.
{"title":"Prediction of Treatment Recommendations Via Ensemble Machine Learning Algorithms for Non-Small Cell Lung Cancer Patients in Personalized Medicine.","authors":"Hojin Moon, Lauren Tran, Andrew Lee, Taeksoo Kwon, Minho Lee","doi":"10.1177/11769351241272397","DOIUrl":"https://doi.org/10.1177/11769351241272397","url":null,"abstract":"<p><strong>Objectives: </strong>The primary goal of this research is to develop treatment-related genomic predictive markers for non-small cell lung cancer by integrating various machine learning algorithms that recommends near-optimal individualized patient treatment for chemotherapy in an effort to maximize efficacy or minimize treatment-related toxicity. This research can contribute toward developing a more refined, accurate and effective therapy accounting for specific patient needs.</p><p><strong>Methods: </strong>To accomplish our research goal, we implement ensemble learning algorithms, bagging with regularized Cox regression models and nonparametric tree-based models via Random Survival Forests. A comprehensive meta-database was compiled from the NCBI Gene Expression Omnibus data repository for lung cancer patients to capture and utilize complex genomic patterns that can predict treatment outcomes more accurately.</p><p><strong>Results: </strong>The developed novel prediction algorithm demonstrates the ability to support complex clinical decision-making processes in the treatment of NSCLC. It effectively addresses patient heterogeneity, offering predictions that are both refined and personalized in improving the precision of chemotherapy regimens prescribed to the eligible patients.</p><p><strong>Conclusion: </strong>This research should contribute substantial advancement of cancer treatments by improving the accuracy and efficacy of chemotherapy treatments for a targeted group of patients who need the right treatment. The integration of complex machine learning techniques with genomic data holds substantial potential to transform current cancer treatment paradigms by providing robust support in clinical decision-making.</p>","PeriodicalId":35418,"journal":{"name":"Cancer Informatics","volume":"23 ","pages":"11769351241272397"},"PeriodicalIF":2.4,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11483699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142476534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-08eCollection Date: 2024-01-01DOI: 10.1177/11769351241286710
Jie-Huei Wang, Po-Lin Hou, Yi-Hau Chen
Objectives: Under the classification of multicategory survival outcomes of cancer patients, it is crucial to identify biomarkers that affect specific outcome categories. The classification of multicategory survival outcomes from transcriptomic data has been thoroughly investigated in computational biology. Nevertheless, several challenges must be addressed, including the ultra-high-dimensional feature space, feature contamination, and data imbalance, all of which contribute to the instability of the diagnostic model. Furthermore, although most methods achieve accurate predicted performance for binary classification with high-dimensional transcriptomic data, their extension to multi-class classification is not straightforward.
Methods: We employ the One-versus-One strategy to transform multi-class classification into multiple binary classification, and utilize the overlapping group screening procedure with binary logistic regression to include pathway information for identifying important genes and gene-gene interactions for multicategory survival outcomes.
Results: A series of simulation studies are conducted to compare the classification accuracy of our proposed approach with some existing machine learning methods. In practical data applications, we utilize the random oversampling procedure to tackle class imbalance issues. We then apply the proposed method to analyze transcriptomic data from various cancers in The Cancer Genome Atlas, such as kidney renal papillary cell carcinoma, lung adenocarcinoma, and head and neck squamous cell carcinoma. Our aim is to establish an accurate microarray-based multicategory cancer diagnosis model. The numerical results illustrate that the new proposal effectively enhances cancer diagnosis compared to approaches that neglect pathway information.
Conclusions: We showcase the effectiveness of the proposed method in terms of class prediction accuracy through evaluations on simulated synthetic datasets as well as real dataset applications. We also identified the cancer-related gene-gene interaction biomarkers and reported the corresponding network structure. According to the identified major genes and gene-gene interactions, we can predict for each patient the probabilities that he/she belongs to each of the survival outcome classes.
{"title":"Multicategory Survival Outcomes Classification via Overlapping Group Screening Process Based on Multinomial Logistic Regression Model With Application to TCGA Transcriptomic Data.","authors":"Jie-Huei Wang, Po-Lin Hou, Yi-Hau Chen","doi":"10.1177/11769351241286710","DOIUrl":"10.1177/11769351241286710","url":null,"abstract":"<p><strong>Objectives: </strong>Under the classification of multicategory survival outcomes of cancer patients, it is crucial to identify biomarkers that affect specific outcome categories. The classification of multicategory survival outcomes from transcriptomic data has been thoroughly investigated in computational biology. Nevertheless, several challenges must be addressed, including the ultra-high-dimensional feature space, feature contamination, and data imbalance, all of which contribute to the instability of the diagnostic model. Furthermore, although most methods achieve accurate predicted performance for binary classification with high-dimensional transcriptomic data, their extension to multi-class classification is not straightforward.</p><p><strong>Methods: </strong>We employ the One-versus-One strategy to transform multi-class classification into multiple binary classification, and utilize the overlapping group screening procedure with binary logistic regression to include pathway information for identifying important genes and gene-gene interactions for multicategory survival outcomes.</p><p><strong>Results: </strong>A series of simulation studies are conducted to compare the classification accuracy of our proposed approach with some existing machine learning methods. In practical data applications, we utilize the random oversampling procedure to tackle class imbalance issues. We then apply the proposed method to analyze transcriptomic data from various cancers in The Cancer Genome Atlas, such as kidney renal papillary cell carcinoma, lung adenocarcinoma, and head and neck squamous cell carcinoma. Our aim is to establish an accurate microarray-based multicategory cancer diagnosis model. The numerical results illustrate that the new proposal effectively enhances cancer diagnosis compared to approaches that neglect pathway information.</p><p><strong>Conclusions: </strong>We showcase the effectiveness of the proposed method in terms of class prediction accuracy through evaluations on simulated synthetic datasets as well as real dataset applications. We also identified the cancer-related gene-gene interaction biomarkers and reported the corresponding network structure. According to the identified major genes and gene-gene interactions, we can predict for each patient the probabilities that he/she belongs to each of the survival outcome classes.</p>","PeriodicalId":35418,"journal":{"name":"Cancer Informatics","volume":"23 ","pages":"11769351241286710"},"PeriodicalIF":2.4,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11462568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142393899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-29eCollection Date: 2024-01-01DOI: 10.1177/11769351241272389
Mehwish Mooghal, Saad Nasir, Aiman Arif, Wajiha Khan, Yasmin Abdul Rashid, Lubna M Vohra
This narrative review explores the burgeoning field of Artificial Intelligence (AI)-driven Breast Cancer (BC) survival prediction, emphasizing the transformative impact on patient care. From machine learning to deep neural networks, diverse models demonstrate the potential to refine prognosis accuracy and tailor treatment strategies. The literature underscores the need for clinician integration and addresses challenges of model generalizability and ethical considerations. Crucially, AI's promise extends to Low- and Middle-Income Countries (LMICs), presenting an opportunity to bridge healthcare disparities. Collaborative efforts in research, technology transfer, and education are essential to empower healthcare professionals in LMICs. As we navigate this frontier, AI emerges not only as a technological advancement but as a guiding light toward personalized, accessible BC care, marking a significant stride in the global fight against this formidable disease.
这篇叙述性综述探讨了人工智能(AI)驱动的乳腺癌(BC)生存预测这一新兴领域,强调其对患者护理的变革性影响。从机器学习到深度神经网络,各种模型都展示了提高预后准确性和定制治疗策略的潜力。文献强调了临床医生整合的必要性,并解决了模型通用性和伦理考虑方面的挑战。最重要的是,人工智能的前景已扩展到中低收入国家(LMIC),为缩小医疗差距提供了机会。研究、技术转让和教育方面的合作对于增强中低收入国家医疗保健专业人员的能力至关重要。在我们探索这一前沿领域的过程中,人工智能不仅是一项技术进步,也是实现个性化、可获得的 BC 护理的指路明灯,标志着全球在抗击这一可怕疾病的斗争中迈出了重要一步。
{"title":"Innovations in Artificial Intelligence-Driven Breast Cancer Survival Prediction: A Narrative Review.","authors":"Mehwish Mooghal, Saad Nasir, Aiman Arif, Wajiha Khan, Yasmin Abdul Rashid, Lubna M Vohra","doi":"10.1177/11769351241272389","DOIUrl":"10.1177/11769351241272389","url":null,"abstract":"<p><p>This narrative review explores the burgeoning field of Artificial Intelligence (AI)-driven Breast Cancer (BC) survival prediction, emphasizing the transformative impact on patient care. From machine learning to deep neural networks, diverse models demonstrate the potential to refine prognosis accuracy and tailor treatment strategies. The literature underscores the need for clinician integration and addresses challenges of model generalizability and ethical considerations. Crucially, AI's promise extends to Low- and Middle-Income Countries (LMICs), presenting an opportunity to bridge healthcare disparities. Collaborative efforts in research, technology transfer, and education are essential to empower healthcare professionals in LMICs. As we navigate this frontier, AI emerges not only as a technological advancement but as a guiding light toward personalized, accessible BC care, marking a significant stride in the global fight against this formidable disease.</p>","PeriodicalId":35418,"journal":{"name":"Cancer Informatics","volume":"23 ","pages":"11769351241272389"},"PeriodicalIF":2.4,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11526191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objectives: Captopril is a commonly used therapeutic agent in the management of renovascular hypertension (high blood pressure), congestive heart failure, left ventricular dysfunction following myocardial infarction, and nephropathy. Captopril has been found to interact with proteins that are significantly associated with bladder cancer (BLCA), suggesting that it could be a potential medication for BLCA patients with concurrent hypertension.
Methods: DrugBank 5.0 was utilized to identify the direct protein targets (DPTs) of captopril. STRING was used to analyze the multiple protein interactions. TNMPlot was used for comparing gene expression in normal, tumor, and metastatic tissue. Then, docking with target proteins was done using Autodock. Molecular dynamics simulations were applied for estimate the diffusion coefficients and mean-square displacements in materials.
Results: Among all these proteins, MMP9 is observed to be an overexpressed gene in BLCA and its increased expression is linked to reduced survival in patients. Our findings indicate that captopril effectively inhibits both the wild type and common mutated forms of MMP9 in BLCA. Furthermore, the LCN2 gene, which is also overexpressed in BLCA, interacts with captopril-associated proteins. The overexpression of LCN2 is similarly associated with reduced survival in BLCA. Through molecular docking analysis, we have identified specific amino acid residues (Tyr179, Pro421, Tyr423, and Lys603) at the active pocket of MMP9, as well as Tyr78, Tyr106, Phe145, Lys147, and Lys156 at the active pocket of LCN2, with which captopril interacts. Thus, our data provide compelling evidence for the inhibitory potential of captopril against human proteins MMP9 and LCN2, both of which play crucial roles in BLCA.
Conclusion: These discoveries present promising prospects for conducting subsequent validation studies both in vitro and in vivo, with the aim of assessing the suitability of captopril for treating BLCA patients, irrespective of their hypertension status, who exhibit elevated levels of MMP9 and LCN2 expression.
{"title":"Computational Insights into Captopril's Inhibitory Potential Against MMP9 and LCN2 in Bladder Cancer: Implications for Therapeutic Application.","authors":"Sanjida Kabir Annana, Jannatul Ferdoush, Farzia Lamia, Ayan Roy, Pallab Kar, Monisha Nandi, Maliha Kabir, Ayan Saha","doi":"10.1177/11769351241276759","DOIUrl":"10.1177/11769351241276759","url":null,"abstract":"<p><strong>Objectives: </strong>Captopril is a commonly used therapeutic agent in the management of renovascular hypertension (high blood pressure), congestive heart failure, left ventricular dysfunction following myocardial infarction, and nephropathy. Captopril has been found to interact with proteins that are significantly associated with bladder cancer (BLCA), suggesting that it could be a potential medication for BLCA patients with concurrent hypertension.</p><p><strong>Methods: </strong>DrugBank 5.0 was utilized to identify the direct protein targets (DPTs) of captopril. STRING was used to analyze the multiple protein interactions. TNMPlot was used for comparing gene expression in normal, tumor, and metastatic tissue. Then, docking with target proteins was done using Autodock. Molecular dynamics simulations were applied for estimate the diffusion coefficients and mean-square displacements in materials.</p><p><strong>Results: </strong>Among all these proteins, <i>MMP9</i> is observed to be an overexpressed gene in BLCA and its increased expression is linked to reduced survival in patients. Our findings indicate that captopril effectively inhibits both the wild type and common mutated forms of <i>MMP9</i> in BLCA. Furthermore, the <i>LCN2</i> gene, which is also overexpressed in BLCA, interacts with captopril-associated proteins. The overexpression of <i>LCN2</i> is similarly associated with reduced survival in BLCA. Through molecular docking analysis, we have identified specific amino acid residues (Tyr179, Pro421, Tyr423, and Lys603) at the active pocket of MMP9, as well as Tyr78, Tyr106, Phe145, Lys147, and Lys156 at the active pocket of LCN2, with which captopril interacts. Thus, our data provide compelling evidence for the inhibitory potential of captopril against human proteins MMP9 and LCN2, both of which play crucial roles in BLCA.</p><p><strong>Conclusion: </strong>These discoveries present promising prospects for conducting subsequent validation studies both in vitro and in vivo, with the aim of assessing the suitability of captopril for treating BLCA patients, irrespective of their hypertension status, who exhibit elevated levels of MMP9 and LCN2 expression.</p>","PeriodicalId":35418,"journal":{"name":"Cancer Informatics","volume":"23 ","pages":"11769351241276759"},"PeriodicalIF":2.4,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objectives: Aim of this study was to explore the immune-related lncRNAs having prognostic role and establishing risk score model for better prognosis and immunotherapeutic coherence for esophageal cancer (EC) patients.
Methods: To determine the role of immune-related lncRNAs in EC, we analyzed the RNA-seq expression data of 162 EC patients and 11 non-cancerous individuals and their clinically relevant information from the cancer genome atlas (TCGA) database. Bioinformatic and statistical analysis such as Differential expression analysis, co-expression analysis, Kaplan Meier survival analysis, Cox proportional hazards model, ROC analysis of risk model was employed.
Results: Utilizing a cutoff criterion (log2FC > 1 + log2FC < -1 and FDR < 0.01), we identified 3737 RNAs were significantly differentially expressed in EC patients. Among these, 2222 genes were classified as significantly differentially expressed mRNAs (demRNAs), and 966 were significantly differentially expressed lncRNAs (delncRNA). Through Pearson correlation analysis between differentially expressed lncRNAs and immune related-mRNAs, we identified 12 immune-related lncRNAs as prognostic signatures for EC. Notably, through Kaplan-Meier analysis on these lncRNAs, we found the low-risk group patients showed significantly improved survival compared to the high-risk group. Moreover, this prognostic signature has consistent performance across training, testing and entire validation cohort sets. Using ESTIMATE and CIBERSORT algorithm we further observed significant enriched infiltration of naive B cells, regulatory T cells resting CD4+ memory T cells, and, plasma cells in the low-risk group compared to high-risk EC patients group. On the contrary, tumor-associated M2 macrophages were highly enriched in high-risk patients. Additionally, we confirmed immune-related biological functions and pathways such as inflammatory, cytokines, chemokines response and natural killer cell-mediated cytotoxicity, toll-like receptor signaling pathways, JAK-STAT signaling pathways, chemokine signaling pathways significantly associated with identified IRlncRNA signature and their co-expressed immune genes. Furthermore, we assessed the predictive potential of the lncRNA signature in immune checkpoint inhibitors; we found that programed cell death ligand 1 (PD-L1; P-value = .048), programed cell death ligand 2 (PD-L2; P-value = .002), and T cell immunoglobulin and mucin-domain containing-3 (TIM-3; P-value = .045) expression levels were significantly higher in low-risk patients compared to high-risk patients.
Conclusion: We believe this study will contribute to better prognosis prediction and targeted treatment of EC in the future.
{"title":"Immune-Related Long Non-Coding RNA Signature Determines Prognosis and Immunotherapeutic Coherence in Esophageal Cancer.","authors":"Vivek Uttam, Harmanpreet Singh Kapoor, Manjit Kaur Rana, Ritu Yadav, Hridayesh Prakash, Manju Jain, Hardeep Singh Tuli, Aklank Jain","doi":"10.1177/11769351241276757","DOIUrl":"https://doi.org/10.1177/11769351241276757","url":null,"abstract":"<p><strong>Objectives: </strong>Aim of this study was to explore the immune-related lncRNAs having prognostic role and establishing risk score model for better prognosis and immunotherapeutic coherence for esophageal cancer (EC) patients.</p><p><strong>Methods: </strong>To determine the role of immune-related lncRNAs in EC, we analyzed the RNA-seq expression data of 162 EC patients and 11 non-cancerous individuals and their clinically relevant information from the cancer genome atlas (TCGA) database. Bioinformatic and statistical analysis such as Differential expression analysis, co-expression analysis, Kaplan Meier survival analysis, Cox proportional hazards model, ROC analysis of risk model was employed.</p><p><strong>Results: </strong>Utilizing a cutoff criterion (log2FC > 1 + log2FC < -1 and FDR < 0.01), we identified 3737 RNAs were significantly differentially expressed in EC patients. Among these, 2222 genes were classified as significantly differentially expressed mRNAs (demRNAs), and 966 were significantly differentially expressed lncRNAs (delncRNA). Through Pearson correlation analysis between differentially expressed lncRNAs and immune related-mRNAs, we identified 12 immune-related lncRNAs as prognostic signatures for EC. Notably, through Kaplan-Meier analysis on these lncRNAs, we found the low-risk group patients showed significantly improved survival compared to the high-risk group. Moreover, this prognostic signature has consistent performance across training, testing and entire validation cohort sets. Using ESTIMATE and CIBERSORT algorithm we further observed significant enriched infiltration of naive B cells, regulatory T cells resting CD4+ memory T cells, and, plasma cells in the low-risk group compared to high-risk EC patients group. On the contrary, tumor-associated M2 macrophages were highly enriched in high-risk patients. Additionally, we confirmed immune-related biological functions and pathways such as inflammatory, cytokines, chemokines response and natural killer cell-mediated cytotoxicity, toll-like receptor signaling pathways, JAK-STAT signaling pathways, chemokine signaling pathways significantly associated with identified IRlncRNA signature and their co-expressed immune genes. Furthermore, we assessed the predictive potential of the lncRNA signature in immune checkpoint inhibitors; we found that programed cell death ligand 1 (PD-L1; P-value = .048), programed cell death ligand 2 (PD-L2; P-value = .002), and T cell immunoglobulin and mucin-domain containing-3 (TIM-3; P-value = .045) expression levels were significantly higher in low-risk patients compared to high-risk patients.</p><p><strong>Conclusion: </strong>We believe this study will contribute to better prognosis prediction and targeted treatment of EC in the future.</p>","PeriodicalId":35418,"journal":{"name":"Cancer Informatics","volume":"23 ","pages":"11769351241276757"},"PeriodicalIF":2.4,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11401149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142297165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}