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第五届全国生物信息学与系统生物学学术大会暨国际生物信息...

作者：李骜 Hong Xial Yuanning Liu Minghui Wang School of Information Science and Technology University of Science and Technology of China Center for Biomedical Engineering Research University of Science and Technology of China

Background:With the advance of single nucleotide polymorphism(SNP) genotyping arrays,there is increasing interest in using this powerful technology for profiling chromosomal aberrations in ***,currently a critical issue hampering further applications of SNP-array in cancer research lies in the fact that cancer is often heterogeneous with multiple sub-clones that exhibit distinct biological characteristic including chromosomal *** addition,cancer heterogeneity is of great interest to oncologists as study on it may shed light on the origin of cancer and carcinogenesis. Methods:To address the issue of cancer heterogeneity,we developed a novel statistical model named CHASE(cancer heterogeneity and Chromosomal Aberrations from SNP-array Experiments) based on the framework of global parameter hidden Markov model(HMM).By quantitatively delineating the genomic similarity and discrepancy between two cancer sub-clones using global parameters representing the percentage of different sub-clones,we generated empirical emission probability density functions and incorporated them with the *** modeling fitting and parameter estimation,ECM algorithm was adopted in CHASE and formulas were derived for parameter updating. Results:Test on both simulated and real SNP-array data showed that CHASE can automatically determine cancer heterogeneity from the results of SNP-array experiment. For each cancer sub-clone,various kinds of chromosomal aberrations,such as amplification,deletion,LOH,etc,can be precisely discovered by *** example, by applying CHASE to breast cancer sample "BLCB1T45" that was manually identified as heterogeneous,we successfully identified two cancer sub-clones with two chromosomal regions exhibiting distinct chromosomal aberrations. Conclusions:To the best of our knowledge,CHASE is currently the most powerful computational methods that can discover cancer heterogeneity and chromosomal aberrations for each sub-clone from SNP-array data.

关键词： SNP-array cancer heterogeneity chromosomal aberration HMM

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MATHEMATICAL MODELING AND BIFURCATION ANALYSIS FOR A BIOLOGICAL MECHANISM OF cancer DRUG RESISTANCE

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Acta Mathematica Scientia 2024年第3期44卷 1165-1188页

作者：包康博梁桂珍田天海张兴安 School of Information Engineering and Artificial Intelligence Lanzhou University of Finance and EconomicsLanzhou730020China School of Mathematics and Statistics Central China Normal UniversityWuhan430079China School of Mathematics and Information Science Xinxiang UniversityXinxiang453003China School of Mathematical Sciences Monash UniversityMelbourneVIC3800Australia

Drug resistance is one of the most intractable issues in targeted therapy for cancer *** has also been demonstrated to be related to cancer heterogeneity,which promotes the emergence of treatment-refractory cancer cell *** on how cancer cells develop resistance during the encounter with targeted drugs and the immune system,we propose a mathematical model for studying the dynamics of drug resistance in a conjoint heterogeneous tumor-immune *** analyze the local geometric properties of the equilibria of the *** simulations show that the selectively targeted removal of sensitive cancer cells may cause the initially heterogeneous population to become a more resistant ***,the decline of immune recruitment is a stronger determinant of cancer escape from immune surveillance or targeted therapy than the decay in immune predation *** analysis of model parameters provides insight into the roles of the immune system combined with targeted therapy in determining treatment outcomes.

关键词： mathematical model drug resistance cancer heterogeneity immune system targeted therapy

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Immunotherapy against programmed death-1/programmed death ligand 1 in hepatocellular carcinoma: Importance of molecular variations, cellular heterogeneity, and cancer stem cells

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World Journal of Stem Cells 2021年第7期13卷 795-824页

作者： Caecilia H C Sukowati Korri Elvanita El-Khobar Claudio Tiribelli Centro Studi Fegato Fondazione Italiana Fegato ONLUSTrieste 34149Italy Hepatitis Unit Eijkman Institute for Molecular BiologyJakarta 10430Indonesia

Hepatocellular carcinoma(HCC)is a heterogeneous malignancy related to diverse etiological *** oncogenic mechanisms and genetic variations lead to multiple HCC molecular ***,an immune-based strategy using immune checkpoint inhibitors(ICIs)was presented in HCC therapy,especially with ICIs against the programmed death-1(PD-1)and its ligand ***,despite the success of anti-PD-1/PD-L1 in other cancers,a substantial proportion of HCC patients fail to *** this review,we gather current information on biomarkers of anti-PD-1/PD-L1 treatment and the contribution of HCC heterogeneity and hepatic cancer stem cells(CSCs).Genetic variations of PD-1 and PD-L1 are associated with chronic liver disease and progression to ***-L1 expression in tumoral tissues is differentially expressed in CSCs,particularly in those with a close association with the tumor *** information will be beneficial for the selection of patients and the management of the ICIs against PD-1/PD-L1.

关键词： Hepatocellular carcinoma Programmed death-1 Programmed death ligand 1 cancer stem cells cancer heterogeneity Genetic variants

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