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Zhang, X., Li, M., Ye, S., Shen, K., Yuan, H., Bakhtyar, S., . . . Sun, X.-F. (2024). CBD2: A functional biomarker database for colorectal cancer. iMeta, 3(1), Article ID e155.
Open this publication in new window or tab >>CBD2: A functional biomarker database for colorectal cancer
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2024 (English)In: iMeta, ISSN 2770-5986, E-ISSN 2770-596X, Vol. 3, no 1, article id e155Article in journal (Refereed) Published
Abstract [en]

The rapidly evolving landscape of biomarkers for colorectal cancer (CRC) necessitates an integrative, updated repository. In response, we constructed the Colorectal Cancer Biomarker Database (CBD), which collected and displayed the curated biomedicine information for 870 CRC biomarkers in the previous study. Building on CBD, we have now developed CBD2, which includes information on 1569 newly reported biomarkers derived from different biological sources (DNA, RNA, protein, and others) and clinical applications (diagnosis, treatment, and prognosis). CBD2 also incorporates information on nonbiomarkers that have been identified as unsuitable for use as biomarkers in CRC. A key new feature of CBD2 is its network analysis function, by which users can investigate the visible and topological network between biomarkers and identify their relevant pathways. CBD2 also allows users to query a series of chemicals, drug combinations, or multiple targets, to enable multidrug, multitarget, multipathway analyses, toward facilitating the design of polypharmacological treatments for CRC. CBD2 is freely available at . CBD2 integrates biomarkers derived from diverse biological sources and clinical applications, employing a standardized approach for annotation and classification. CBD2 facilitates precision medicine in colorectal cancer by providing abundant data, including drug-target information and visualized network analysis functions. With its user-friendly interface, CBD2 aids in the identification and development of biomarkers for colorectal cancer.Highlightsimage CBD2 integrates biomarkers derived from diverse biological sources and clinical applications, employing a standardized approach for annotation and classification.CBD2 facilitates precision medicine in colorectal cancer by providing abundant data, including drug-target information and visualized network analysis functions.With its user-friendly interface, CBD2 aids in the identification and development of biomarkers for colorectal cancer.

Place, publisher, year, edition, pages
WILEY, 2024
Keywords
biomarker; colorectal cancer; database; network analysis
National Category
Bioinformatics and Computational Biology
Identifiers
urn:nbn:se:liu:diva-199682 (URN)10.1002/imt2.155 (DOI)001112778000001 ()
Note

Funding Agencies|National Natural Science Foundation of China; GDPH Supporting Fund for Talent Program [KJ012020633, KJ012019530]; Guangdong Provincial Peoples Hospital; Guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application [2022B1212010011]; [32200545]; [32271292]

Available from: 2023-12-19 Created: 2023-12-19 Last updated: 2025-02-07Bibliographically approved
Kopsida, M., Liu, N., Kotti, A., Wang, J., Jensen, L. D., Jothimani, G., . . . Sun, X.-F. (2024). RhoB expression associated with chemotherapy response and prognosis in colorectal cancer. Cancer Cell International, 24(1), Article ID 75.
Open this publication in new window or tab >>RhoB expression associated with chemotherapy response and prognosis in colorectal cancer
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2024 (English)In: Cancer Cell International, E-ISSN 1475-2867, Vol. 24, no 1, article id 75Article in journal (Refereed) Published
Abstract [en]

Purpose: To examine the role of RhoB expression in relation to chemotherapy response, clinical outcomes and associated signaling pathways in colorectal cancer patients.

Materials and methods: The study included 5 colon cancer cell lines, zebrafish embryos and 260 colorectal cancer patients treated with 5-fluorouracil (5-FU) and oxaliplatin (OXL). The methods consisted of CRISPR/Cas9, reactive oxygen species (ROS), caspase-3 activity, autophagy flux, in-silico RNA sequencing and immunohistochemistry. Gene expression analysis and pathway analysis were conducted using RNA-seq data.

Results: All cancer lines tested, including SW480, SW480-KO13 (RhoB knockout), SW480-KO55 (RhoB knockout), HCT116 and HCT116-OE (RhoB overexpressed), exhibited cytotoxicity to 5-FU and OXL. RhoB knockout cell lines demonstrated significantly reduced migration compared to the control cell lines. Furthermore, RhoB played a role in caspase-3-dependent apoptosis, regulation of ROS production and autophagic flux. The mRNA sequencing data indicated lower expression levels of oncogenes in RhoB knockout cell lines. The zebrafish model bearing SW480-KO showed a light trend toward tumor regression. RhoB expression by immunohistochemistry in patients was increased from normal mucosa to tumor samples. In patients who received chemotherapy, high RhoB expression was related to worse survival compared to low RhoB expression. Furthermore, the molecular docking analysis revealed that OXL had a higher binding affinity for RhoB than 5-FU, with a binding affinity of -7.8 kcal/mol and HADDOCK predicted molecular interactions between RhoB and caspase 3 protein. Gene-set enrichment analysis supported these findings, showing that enrichment of DNA damage response pathway and p53 signaling in RhoB overexpression treatment group, while the RhoB knockout treatment group exhibited enrichment in the negative regulation pathway of cell migration.

Conclusion: RhoB was negatively associated with chemotherapy response and survival in colorectal cancers. Therefore, RhoB inhibition may enhance chemotherapeutic responses and patient survival.

Place, publisher, year, edition, pages
BioMed Central (BMC), 2024
Keywords
RhoB; Colorectal cancer; 5-fluorouracil; Oxaliplatin; Survival; Signaling pathway;
National Category
Cancer and Oncology Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-201131 (URN)10.1186/s12935-024-03236-1 (DOI)001162467200001 ()38355625 (PubMedID)
Available from: 2024-02-22 Created: 2024-02-22 Last updated: 2024-03-01
Pham, T. D., Ravi, V., Luo, B., Fan, C. & Sun, X.-F. (2023). Artificial intelligence fusion for predicting survival of rectal cancer patients using immunohistochemical expression of Ras homolog family member B in biopsy. Exploration of Targeted Anti-tumor Therapy, 4(1), 1-16
Open this publication in new window or tab >>Artificial intelligence fusion for predicting survival of rectal cancer patients using immunohistochemical expression of Ras homolog family member B in biopsy
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2023 (English)In: Exploration of Targeted Anti-tumor Therapy, E-ISSN 2692-3114, Vol. 4, no 1, p. 1-16Article in journal (Refereed) Published
Abstract [en]

Aim: The process of biomarker discovery is being accelerated with the application of artificial intelligence (AI), including machine learning. Biomarkers of diseases are useful because they are indicators of pathogenesis or measures of responses to therapeutic treatments, and therefore, play a key role in new drug development. Proteins are among the candidates for biomarkers of rectal cancer, which need to be explored using state-of-the-art AI to be utilized for prediction, prognosis, and therapeutic treatment. This paper aims to investigate the predictive power of Ras homolog family member B (RhoB) protein in rectal cancer.

Methods: This study introduces the integration of pretrained convolutional neural networks and support vector machines (SVMs) for classifying biopsy samples of immunohistochemical expression of protein RhoB in rectal-cancer patients to validate its biologic measure in biopsy. Features of the immunohistochemical expression images were extracted by the pretrained networks and used for binary classification by the SVMs into two groups of less and more than 5-year survival rates.

Results: The fusion of neural search architecture network (NASNet)-Large for deep-layer feature extraction and classifier using SVMs provided the best average classification performance with a total accuracy = 85%, prediction of survival rate of more than 5 years = 90%, and prediction of survival rate of less than 5 years = 75%.

Conclusions: The finding obtained from the use of AI reported in this study suggest that RhoB expression on rectal-cancer biopsy can be potentially used as a biomarker for predicting survival outcomes in rectal-cancer patients, which can be informative for clinical decision making if the patient would be recommended for preoperative therapy.

Place, publisher, year, edition, pages
Open Exploration Publishing, 2023
Keywords
Artificial intelligence; biomarkers; immunohistochemistry; machine learning; precision medicine; proteins; rectal neoplasms
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-200794 (URN)10.37349/etat.2023.00119 (DOI)36937315 (PubMedID)
Available from: 2024-02-07 Created: 2024-02-07 Last updated: 2024-12-02
Shruthi, N. R., Jain, M. S., Ganesan, H., Banerjee, A., Zhang, H., Sun, X.-F. & Pathak, S. (2023). Drug Repurposing in Cancer (1ed.). In: Ranbir Chander Sobti, Sunil K. Lal, Ramesh K. Goyal (Ed.), Drug Repurposing for Emerging Infectious Diseases and Cancer: (pp. 159-179). Singapore: Springer
Open this publication in new window or tab >>Drug Repurposing in Cancer
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2023 (English)In: Drug Repurposing for Emerging Infectious Diseases and Cancer / [ed] Ranbir Chander Sobti, Sunil K. Lal, Ramesh K. Goyal, Singapore: Springer, 2023, 1, p. 159-179Chapter in book (Other academic)
Abstract [en]

The discovery of drug compounds has a long history in drug repurposing, notably by fortuitous findings. It has taken a new path in the creation of novel therapeutics based on existent or authorized drugs in recent years. Importantly, our knowledge of cancer biology and the related cancer hallmarks is growing. This, together with repurposing studies that use modern bioinformatics and comprehensive screening of the complete pharmacopeia, should lead to the discovery of novel medicines and targets. Furthermore, the usage of non-oncology pharmaceuticals, which make up most of our treatments, has the potential to speed up drug repurposing even further. We looked at both phenotypic-based and target-based methods of medication repurposing as well as described and assessed old non-oncology medications as prospective candidates for drug repurposing based on a broad knowledge of these principles and associated investigations of drug repurposing over the previous decade. Some of these medications successfully regulate at least one characteristic of cancer, whereas the others have a broad anticancer activity by regulating several targets through different signaling pathways, which is often brought on by various simultaneous signaling pathways. Furthermore, the emergence of computerized databases of disease gene targets, functional readouts, and clinical data encompassing inter-individual genetic variants and toxicities has allowed an alternative “big data” approach to grow at an unheard-of rate during the past decade. Here, we review the sources that are now on hand and speculate on significant upside possibilities.

Place, publisher, year, edition, pages
Singapore: Springer, 2023 Edition: 1
Keywords
Drug repurposing; Colorectal cancer; Target-based; Signaling pathways; Bioinformatics
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-192116 (URN)10.1007/978-981-19-5399-6_8 (DOI)9789811953989 (ISBN)9789811953996 (ISBN)
Available from: 2023-03-03 Created: 2023-03-03 Last updated: 2024-01-10Bibliographically approved
Ganesan, H., Makalakshmi, M. K., Banerjee, A., Zhang, H., Sun, X.-F. & Pathak, S. (2022). Mucinous Colorectal Cancer Oxidative Stress and Therapeutic MicroRNAs. In: Chakraborti, Sajal (Ed.), Handbook of Oxidative Stress in Cancer: Therapeutic Aspects: (pp. 1-18). Singapore: Springer
Open this publication in new window or tab >>Mucinous Colorectal Cancer Oxidative Stress and Therapeutic MicroRNAs
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2022 (English)In: Handbook of Oxidative Stress in Cancer: Therapeutic Aspects / [ed] Chakraborti, Sajal, Singapore: Springer , 2022, p. 1-18Chapter in book (Refereed)
Abstract [en]

Colorectal Cancer (CRC) is the third most leading cause of cancer related death worldwide and has a diverse clinical etiology. Mounting evidences has shown that CRC, in its rare yet lethal form as mucinous adenocarcinoma. Has led to poor prognosis and eventual complexity in the treatment. This subcategory of CRC characteristically secrete mucin hence, they are histologically identified based on the presence of mucin in CRC. In this context, the current article aims to provide a detailed overview and understanding of the underlying molecular mechanisms governing mucinous cancer onset and progression. We elaborate on the role of different pathways and molecular targets including microsatellite instability (MSI), chromosome instability (CIN) and CpG island methylator phenotype (CIMP), oncogenes such as KRAS, BRAF, p53 and p21 on mucinous CRC. The mucin genes, specifically MUC1, MUC4 and few other variants of the gel-secreted, transmembrane form of CRC play a vital role in the disease development. This makes the miRNA-mediated mucin regulations an exceptionally obliging aid in mucinous CRC understanding. The miRNAs discussed in context include miR-205, miR-373 and miR-124a to name a few. We further discuss the existing therapeutic strategies used to treat this variant of CRC. These diagnostic tools could help in the rapid identification and treatment of the disease.

Place, publisher, year, edition, pages
Singapore: Springer, 2022
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-197125 (URN)10.1007/978-981-16-1247-3_85-1 (DOI)9789811654213 (ISBN)9789811654220 (ISBN)
Available from: 2023-08-24 Created: 2023-08-24 Last updated: 2024-01-10Bibliographically approved
Banerjee, A., Chabria, Y., Kanna N. R., R., Gopi, J., Rowlo, P., Sun, X.-F. & Pathak, S. (2021). Role of Tumor Specific niche in Colon Cancer Progression and Emerging Therapies by Targeting Tumor Microenvironment (1ed.). In: Kursad Turksen (Ed.), Cell Biology and Translational Medicine, Volume 13: Stem Cells in Development and Disease (pp. 177-192). Springer
Open this publication in new window or tab >>Role of Tumor Specific niche in Colon Cancer Progression and Emerging Therapies by Targeting Tumor Microenvironment
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2021 (English)In: Cell Biology and Translational Medicine, Volume 13: Stem Cells in Development and Disease / [ed] Kursad Turksen, Springer, 2021, 1, p. 177-192Chapter in book (Refereed)
Abstract [en]

Colorectal cancer is the third most common form of cancer worldwide leading to escalating mortality rates and mainly includes hereditary, sporadic and colitis-associated cancer development. The escalated mortality rates is due to the limited treatment options as this form of cancer is usually not easy to diagnose in its early stages and are highly invasive leading to rapid metastasis of the malignant cells to the neighbouring tissue. In order to combat this limitation several chemotherapeutic regimens are now being combined with targeted therapies after the knowledge acquired on the inevitable effects of the tumor microenvironment on the colon cancer growth and progress. The colon tumor niche mainly consists of a large mass of tumor cells along with various immune cells, inflammatory cells, tumor macrophages and fibroblasts that infiltrate the tumor as it is a site of predominant inflammation. Among cells of the microenvironment, mesenchymal stem cells (MSCs) exhibiting ability to evolve into cancer associated fibroblasts (CAFs) have recently generated a major interest in the field. The physiological state of the tumor microenvironment is closely connected to discrete steps of tumorigenesis. The colon cancer cells elicit various factors with their direct interaction with MSCs or via paracrine fashion, which modulate these cells to promote cancer instead of performing their innate function of abating cancer progression. This review intends to highlight the necessity to exploit the cellular landscape of tumor microenvironment of colon cancer and a detailed understanding of the interactions between tumor epithelial cells and their stromal/inflammatory elements will aid in future perspectives for designing therapeutic regimens targeting tumor microenvironment to improve the clinical outcome of colon cancer.

Place, publisher, year, edition, pages
Springer, 2021 Edition: 1
Series
Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019
Keywords
Colon cancer; Cytokines; Mesenchymal stem cells; Metastasis; Targeted therapy; Tumor niche; microRNAs.
National Category
Medical and Health Sciences Clinical Medicine Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-183838 (URN)10.1007/5584_2019_355 (DOI)9783030790578 (ISBN)9783030790585 (ISBN)
Available from: 2022-03-25 Created: 2022-03-25 Last updated: 2024-01-10Bibliographically approved
Pham, T. D., Fan, C., Zhang, H. & Sun, X.-F. (2020). Artificial intelligence-based 5-year survival prediction and prognosis of DNp73 expression in rectal cancer patients [Letter to the editor]. CLINICAL AND TRANSLATIONAL MEDICINE, 10(4), Article ID e159.
Open this publication in new window or tab >>Artificial intelligence-based 5-year survival prediction and prognosis of DNp73 expression in rectal cancer patients
2020 (English)In: CLINICAL AND TRANSLATIONAL MEDICINE, ISSN 2001-1326, Vol. 10, no 4, article id e159Article in journal, Letter (Other academic) Published
Abstract [en]

n/a

Place, publisher, year, edition, pages
JOHN WILEY & SONS LTD, 2020
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-170693 (URN)10.1002/ctm2.159 (DOI)000570862000017 ()32898334 (PubMedID)
Available from: 2020-10-19 Created: 2020-10-19 Last updated: 2024-01-10Bibliographically approved
Gopi, J., Gopinath, M., Sun, X.-F., Pathak, S. & Banerjee, A. (2020). Functionality of Intron-Specific Genes and Cancer Stem Cells in the Progression of Colorectal Cancer. In: Pathak, Surajit; Banerjee, Antara (Ed.), Cancer Stem Cells: New Horizons in Cancer Therapies: (pp. 223-239). Singapore: Springer
Open this publication in new window or tab >>Functionality of Intron-Specific Genes and Cancer Stem Cells in the Progression of Colorectal Cancer
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2020 (English)In: Cancer Stem Cells: New Horizons in Cancer Therapies / [ed] Pathak, Surajit; Banerjee, Antara, Singapore: Springer , 2020, p. 223-239Chapter in book (Refereed)
Abstract [en]

This review article deals with comprehensive information about the evolutionary history of introns with their localization and functions in the gene transcripts of colorectal cancer precisely. In this way, the major breakthrough in the molecular biology discipline was the discovery of introns by Richard Robert and Phil Sharp in 1977. Firstly, noncoding regions are recognized by various assortments of regulatory ncRNA sequences such as circular RNA, telomere-associated RNA, small nuclear RNA, Piwi-interacting RNA, small interfering RNA, small nucleolar RNA, microRNA, and long noncoding RNA. Fortunately, splicing process of mRNA strand deals with the excision of introns via spliceosomal proteins into mature mRNA which is witnessed only in eukaryotic organisms and devoid of the splicing machinery components in the prokaryotic organisms. The major focal point relies on intronic genes mainly involved in the progression of colorectal cancer with preliminary information. An alternative splicing process takes place in mRNA that implicates in intron retention leading to varied gene expression in cells and tissues and their promotion in colorectal cancer. Therefore, colorectal cancer-associated diseases have paved the way to know more about the intronic genes mainly concentrated among them in the progression of the related diseases. Hence, the focus of the researchers is toward the fascinating cellular and molecular biology aspects of the regulatory intronic sequences known to enhance as well as repress particular gene expression in tumor microenvironment of colorectal cancer by analyzing the genome and proteome levels for the betterment of human kind that is intended for various therapeutic purposes.

Place, publisher, year, edition, pages
Singapore: Springer, 2020
Keywords
Introns (noncoding sequences); mRNA ; Spliceosomal proteins; Alternate splicing process; Intron retention; Colorectal cancer
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-197123 (URN)10.1007/978-981-15-5120-8_13 (DOI)9789811551192 (ISBN)9789811551208 (ISBN)
Available from: 2023-08-24 Created: 2023-08-24 Last updated: 2024-01-10Bibliographically approved
Subramaniam, V. D., Ramachandran, M., Marotta, F., Banerjee, A., Sun, X.-F. & Pathak, S. (2019). Comparative study on anti-proliferative potentials of zinc oxide and aluminium oxide nanoparticles in colon cancer cells. Acta bio-medica : Atenei Parmensis, 90(2), 241-247
Open this publication in new window or tab >>Comparative study on anti-proliferative potentials of zinc oxide and aluminium oxide nanoparticles in colon cancer cells
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2019 (English)In: Acta bio-medica : Atenei Parmensis, ISSN 0392-4203, Vol. 90, no 2, p. 241-247Article in journal (Refereed) Published
Abstract [en]

Use of commercial products containing nanoparticles formulated from zinc oxide (ZnO) and aluminium oxide (Al2O-3) has increased significantly. These nanoparticles are widely used as ingredient in cosmetics, and also in food packaging industry although their toxicity status is yet to be studied. Here, we aimed to explore the effect of zinc oxide nanoparticles (ZnO-NPs) and aluminium oxide nanoparticles (ANPs) in human HT29 colon cancer cell line.

Place, publisher, year, edition, pages
Mattioli 1885, 2019
Keywords
Cell proliferation, Nanoparticles, Anti proliferative, Toxicity, Colon cancer and Cytotoxicity
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-164799 (URN)10.23750/abm.v90i2.6939 (DOI)31125002 (PubMedID)
Available from: 2020-03-31 Created: 2020-03-31 Last updated: 2024-01-10
Zhang, X., Sun, X.-F., Cao, Y., Ye, B., Peng, Q., Liu, X., . . . Zhang, H. (2018). CBD: a biomarker database for colorectal cancer. Database: The Journal of Biological Databases and Curation, 2018(1 January 2018), Article ID bay046.
Open this publication in new window or tab >>CBD: a biomarker database for colorectal cancer
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2018 (English)In: Database: The Journal of Biological Databases and Curation, E-ISSN 1758-0463, Vol. 2018, no 1 January 2018, article id bay046Article in journal (Refereed) Published
Abstract [en]

Colorectal cancer (CRC) biomarker database (CBD) was established based on 870 identified CRC biomarkers and their relevant information from 1115 original articles in PubMed published from 1986 to 2017. In this version of the CBD, CRC biomarker data were collected, sorted, displayed and analysed. The CBD with the credible contents as a powerful and time-saving tool provide more comprehensive and accurate information for further CRC biomarker research. The CBD was constructed under MySQL server. HTML, PHP and JavaScript languages have been used to implement the web interface. The Apache was selected as HTTP server. All of these web operations were implemented under the Windows system. The CBD could provide to users the multiple individual biomarker information and categorized into the biological category, source and application of biomarkers; the experiment methods, results, authors and publication resources; the research region, the average age of cohort, gender, race, the number of tumours, tumour location and stage. We only collect data from the articles with clear and credible results to prove the biomarkers are useful in the diagnosis, treatment or prognosis of CRC. The CBD can also provide a professional platform to researchers who are interested in CRC research to communicate, exchange their research ideas and further design high-quality research in CRC. They can submit their new findings to our database via the submission page and communicate with us in the CBD.

Place, publisher, year, edition, pages
OXFORD UNIV PRESS, 2018
National Category
Bioinformatics (Computational Biology)
Identifiers
urn:nbn:se:liu:diva-149736 (URN)10.1093/database/bay046 (DOI)000436293800001 ()29846545 (PubMedID)
Note

Funding Agencies|Swedish Cancer Foundation; Swedish Research Council

Available from: 2018-07-24 Created: 2018-07-24 Last updated: 2024-01-15
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Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-1253-1901

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