Database Construction And Functional Factors Identification Of Human Cancer Radiosensitivity

Radiotherapy(RT)is the primary method for cancer treatment given to approximately 60%of all newly diagnosed patients.Significant physical advances in RT have been achieved by developing methods of treatment planning and delivery.However,due to differences in tumor radiosensitivity,not all patients derive survival benefit from RT,while suffering serious adverse consequences.Thus,radiosensitivity has always been a topic of primary importance in the field of radiation oncology.The core of this paper was as follows:1.During the past decades,great efforts have been made to improve radiotherapy treatment through multiple strategies.However,invaluable data remains buried in the extensive radiotherapy literature,making it difficult to obtain an overall view of the detailed mechanisms,thus limiting advances in radiotherapy.To address this issue,we collected data from the relevant literature and developed a literature-based database(dbCRSR,http://bioinfo.ahu.edu.cn:8080/dbCRSR/).2.Identification of radiosensitive genes and multi-target radiosensitizers.Network biology provides insights into complex biological systems and can reveal informative patterns within the systems.Based on the dbCRSR database,we carried out the following analysis:(1)By integrating gene co-expression and protein-protein interaction data(PPI),4 candidate genes were identified.Further experiments indicated that the level of CDC20 gene was the highest among these 4 candidate genes and down-regulation of CDC20 could increases the radiosensitivity in HCT116.(2)Advances in systems biology are revealing phenotypic robustness and network structure that strongly suggests that exquisitely selective compounds,compared with multitarget drugs,may exhibit lower than desired clinical efficacy.To identify the multi-targets radiosensitizer,a network was we constructed which consist of 1067 drugs targeting 167 proteins.A multi-targets drug Brigtinib was selected.Further results suggested Brigtinib could enhance radiosensitivity in multiple cancer cell lines.(3)In addition to chemical drugs,miRNAs are also capable of radiosentivity regulation.Therefore,seeking functional miRNAs becomes a novel strategy to develop radiosensitizers.Through a similar strategy,a series of multi-target miRNAs with potential radiosensitivity were selected.3.It is very important to predict who will benefit from RT before clinical treatment.In the current era of precision medicine,high-throughput technologies have provided an opportunity to approach the development of radiosensitivity biomarkers from a different perspective.Since the immune infiltration and alternative splicing could provide novel insight into tumor treatment options.By integrally analyzing the TCGA data,(1)Our analysis indicated the complex associations between immune infiltration and patients RT outcomes.Besides,immune cells showed large differences in their populations in various cancers,and the most abundant cells were resting memory CD4 T cells.Additionally,the proportion of activated CD4 memory T cells and activated mast cells,albeit at low number,were closely related to RT overall survival in multiple cancers.Furthermore,a prognostic model for RT outcomes was established with good performance based on the immune infiltration status.(2)Based on the SpliceSeq databases,a number of splicing events were found clinically relevant with RT outcome.Kaplan-Meier analysis indicated that alternative splicing events could be potentially used for molecular subtype classification of cancers.The above results indicate that immune infiltrating cells and alternative splicing events have the ability to predict patients' RT outcome.In summary,the above results provided a novel inside into tumor radiosensitivity.And these findings may help to shed light on the detailed mechanism of radiosensitivity and identify valuable biomarkers and therapeutic targets.