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  1. Article: ECM-Receptor Regulatory Network and Its Prognostic Role in Colorectal Cancer.

    Nersisyan, Stepan / Novosad, Victor / Engibaryan, Narek / Ushkaryov, Yuri / Nikulin, Sergey / Tonevitsky, Alexander

    Frontiers in genetics

    2021  Volume 12, Page(s) 782699

    Abstract: Interactions of the extracellular matrix (ECM) and cellular receptors constitute one of the crucial pathways involved in colorectal cancer progression and metastasis. With the use of bioinformatics analysis, we comprehensively evaluated the prognostic ... ...

    Abstract Interactions of the extracellular matrix (ECM) and cellular receptors constitute one of the crucial pathways involved in colorectal cancer progression and metastasis. With the use of bioinformatics analysis, we comprehensively evaluated the prognostic information concentrated in the genes from this pathway. First, we constructed a ECM-receptor regulatory network by integrating the transcription factor (TF) and 5'-isomiR interaction databases with mRNA/miRNA-seq data from The Cancer Genome Atlas Colon Adenocarcinoma (TCGA-COAD). Notably, one-third of interactions mediated by 5'-isomiRs was represented by noncanonical isomiRs (isomiRs, whose 5'-end sequence did not match with the canonical miRBase version). Then, exhaustive search-based feature selection was used to fit prognostic signatures composed of nodes from the network for overall survival prediction. Two reliable prognostic signatures were identified and validated on the independent The Cancer Genome Atlas Rectum Adenocarcinoma (TCGA-READ) cohort. The first signature was made up by six genes, directly involved in ECM-receptor interaction: AGRN, DAG1, FN1, ITGA5, THBS3, and TNC (concordance index 0.61, logrank test
    Language English
    Publishing date 2021-12-06
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2606823-0
    ISSN 1664-8021
    ISSN 1664-8021
    DOI 10.3389/fgene.2021.782699
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: ExhauFS: exhaustive search-based feature selection for classification and survival regression.

    Nersisyan, Stepan / Novosad, Victor / Galatenko, Alexei / Sokolov, Andrey / Bokov, Grigoriy / Konovalov, Alexander / Alekseev, Dmitry / Tonevitsky, Alexander

    PeerJ

    2022  Volume 10, Page(s) e13200

    Abstract: Feature selection is one of the main techniques used to prevent overfitting in machine learning applications. The most straightforward approach for feature selection is an exhaustive search: one can go over all possible feature combinations and pick up ... ...

    Abstract Feature selection is one of the main techniques used to prevent overfitting in machine learning applications. The most straightforward approach for feature selection is an exhaustive search: one can go over all possible feature combinations and pick up the model with the highest accuracy. This method together with its optimizations were actively used in biomedical research, however, publicly available implementation is missing. We present ExhauFS-the user-friendly command-line implementation of the exhaustive search approach for classification and survival regression. Aside from tool description, we included three application examples in the manuscript to comprehensively review the implemented functionality. First, we executed ExhauFS on a toy cervical cancer dataset to illustrate basic concepts. Then, multi-cohort microarray breast cancer datasets were used to construct gene signatures for 5-year recurrence classification. The vast majority of signatures constructed by ExhauFS passed 0.65 threshold of sensitivity and specificity on all datasets, including the validation one. Moreover, a number of gene signatures demonstrated reliable performance on independent RNA-seq dataset without any coefficient re-tuning,
    Language English
    Publishing date 2022-03-30
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2703241-3
    ISSN 2167-8359
    ISSN 2167-8359
    DOI 10.7717/peerj.13200
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: 9-ING-41, a Small Molecule Inhibitor of GSK-3β, Potentiates the Effects of Chemotherapy on Colorectal Cancer Cells.

    Poloznikov, Andrey / Nikulin, Sergey / Bolotina, Larisa / Kachmazov, Andrei / Raigorodskaya, Maria / Kudryavtseva, Anna / Bakhtogarimov, Ildar / Rodin, Sergey / Gaisina, Irina / Topchiy, Maxim / Asachenko, Andrey / Novosad, Victor / Tonevitsky, Alexander / Alekseev, Boris

    Frontiers in pharmacology

    2021  Volume 12, Page(s) 777114

    Abstract: Colorectal cancer (CRC) is one of the most common and lethal types of cancer. Although researchers have made significant efforts to study the mechanisms underlying CRC drug resistance, our knowledge of this disease is still limited, and novel therapies ... ...

    Abstract Colorectal cancer (CRC) is one of the most common and lethal types of cancer. Although researchers have made significant efforts to study the mechanisms underlying CRC drug resistance, our knowledge of this disease is still limited, and novel therapies are in high demand. It is urgent to find new targeted therapy considering limited chemotherapy options.
    Language English
    Publishing date 2021-12-09
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587355-6
    ISSN 1663-9812
    ISSN 1663-9812
    DOI 10.3389/fphar.2021.777114
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Spontaneous metastasis xenograft models link CD44 isoform 4 to angiogenesis, hypoxia, EMT and mitochondria-related pathways in colorectal cancer.

    Everest-Dass, Arun / Nersisyan, Stepan / Maar, Hanna / Novosad, Victor / Schröder-Schwarz, Jennifer / Freytag, Vera / Stuke, Johanna L / Beine, Mia C / Schiecke, Alina / Haider, Marie-Therese / Kriegs, Malte / Elakad, Omar / Bohnenberger, Hanibal / Conradi, Lena-Christin / Raygorodskaya, Maria / Krause, Linda / von Itzstein, Mark / Tonevitsky, Alexander / Schumacher, Udo /
    Maltseva, Diana / Wicklein, Daniel / Lange, Tobias

    Molecular oncology

    2023  Volume 18, Issue 1, Page(s) 62–90

    Abstract: Hematogenous metastasis limits the survival of colorectal cancer (CRC) patients. Here, we illuminated the roles of CD44 isoforms in this process. Isoforms 3 and 4 were predominantly expressed in CRC patients. CD44 isoform 4 indicated poor outcome and ... ...

    Abstract Hematogenous metastasis limits the survival of colorectal cancer (CRC) patients. Here, we illuminated the roles of CD44 isoforms in this process. Isoforms 3 and 4 were predominantly expressed in CRC patients. CD44 isoform 4 indicated poor outcome and correlated with epithelial-mesenchymal transition (EMT) and decreased oxidative phosphorylation (OxPhos) in patients; opposite associations were found for isoform 3. Pan-CD44 knockdown (kd) independently impaired primary tumor formation and abrogated distant metastasis in CRC xenografts. The xenograft tumors mainly expressed the clinically relevant CD44 isoforms 3 and 4. Both isoforms were enhanced in the paranecrotic, hypoxic tumor regions but were generally absent in lung metastases. Upon CD44 kd, tumor angiogenesis was increased in the paranecrotic areas, accompanied by reduced hypoxia-inducible factor-1α and CEACAM5 but increased E-cadherin expression. Mitochondrial genes and proteins were induced upon pan-CD44 kd, as were OxPhos genes. Hypoxia increased VEGF release from tumor spheres, particularly upon CD44 kd. Genes affected upon CD44 kd in xenografts specifically overlapped concordantly with genes correlating with CD44 isoform 4 (but not isoform 3) in patients, validating the clinical relevance of the used model and highlighting the metastasis-promoting role of CD44 isoform 4.
    MeSH term(s) Humans ; Heterografts ; Cell Line, Tumor ; Angiogenesis ; Protein Isoforms/genetics ; Protein Isoforms/metabolism ; Colorectal Neoplasms/pathology ; Epithelial-Mesenchymal Transition/genetics ; Hyaluronan Receptors/genetics ; Hyaluronan Receptors/metabolism ; Hypoxia/genetics ; Gene Expression Regulation, Neoplastic
    Chemical Substances Protein Isoforms ; Hyaluronan Receptors ; CD44 protein, human
    Language English
    Publishing date 2023-11-03
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2415106-3
    ISSN 1878-0261 ; 1574-7891
    ISSN (online) 1878-0261
    ISSN 1574-7891
    DOI 10.1002/1878-0261.13535
    Database MEDical Literature Analysis and Retrieval System OnLINE

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