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      Emerging role of non-invasive and liquid biopsy biomarkers in pancreatic cancer

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          Abstract

          A global increase in the incidence of pancreatic cancer (PanCa) presents a major concern and health burden. The traditional tissue-based diagnostic techniques provided a major way forward for molecular diagnostics; however, they face limitations based on diagnosis-associated difficulties and concerns surrounding tissue availability in the clinical setting. Late disease development with asymptomatic behavior is a drawback in the case of existing diagnostic procedures. The capability of cell free markers in discriminating PanCa from autoimmune pancreatitis and chronic pancreatitis along with other precancerous lesions can be a boon to clinicians. Early-stage diagnosis of PanCa can be achieved only if these biomarkers specifically discriminate the non-carcinogenic disease stage from malignancy with respect to tumor stages. In this review, we comprehensively described the non-invasive disease detection approaches and why these approaches are gaining popularity for their early-stage diagnostic capability and associated clinical feasibility.

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          Cancer statistics, 2022

          Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence and outcomes. Incidence data (through 2018) were collected by the Surveillance, Epidemiology, and End Results program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2019) were collected by the National Center for Health Statistics. In 2022, 1,918,030 new cancer cases and 609,360 cancer deaths are projected to occur in the United States, including approximately 350 deaths per day from lung cancer, the leading cause of cancer death. Incidence during 2014 through 2018 continued a slow increase for female breast cancer (by 0.5% annually) and remained stable for prostate cancer, despite a 4% to 6% annual increase for advanced disease since 2011. Consequently, the proportion of prostate cancer diagnosed at a distant stage increased from 3.9% to 8.2% over the past decade. In contrast, lung cancer incidence continued to decline steeply for advanced disease while rates for localized-stage increased suddenly by 4.5% annually, contributing to gains both in the proportion of localized-stage diagnoses (from 17% in 2004 to 28% in 2018) and 3-year relative survival (from 21% to 31%). Mortality patterns reflect incidence trends, with declines accelerating for lung cancer, slowing for breast cancer, and stabilizing for prostate cancer. In summary, progress has stagnated for breast and prostate cancers but strengthened for lung cancer, coinciding with changes in medical practice related to cancer screening and/or treatment. More targeted cancer control interventions and investment in improved early detection and treatment would facilitate reductions in cancer mortality.
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            The Immune Landscape of Cancer

            We performed an extensive immunogenomic analysis of more than 10,000 tumors comprising 33 diverse cancer types by utilizing data compiled by TCGA. Across cancer types, we identified six immune subtypes-wound healing, IFN-γ dominant, inflammatory, lymphocyte depleted, immunologically quiet, and TGF-β dominant-characterized by differences in macrophage or lymphocyte signatures, Th1:Th2 cell ratio, extent of intratumoral heterogeneity, aneuploidy, extent of neoantigen load, overall cell proliferation, expression of immunomodulatory genes, and prognosis. Specific driver mutations correlated with lower (CTNNB1, NRAS, or IDH1) or higher (BRAF, TP53, or CASP8) leukocyte levels across all cancers. Multiple control modalities of the intracellular and extracellular networks (transcription, microRNAs, copy number, and epigenetic processes) were involved in tumor-immune cell interactions, both across and within immune subtypes. Our immunogenomics pipeline to characterize these heterogeneous tumors and the resulting data are intended to serve as a resource for future targeted studies to further advance the field.
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              Signatures of mutational processes in human cancer

              All cancers are caused by somatic mutations. However, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here, we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, kataegis, is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer with potential implications for understanding of cancer etiology, prevention and therapy.
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                Author and article information

                Contributors
                Journal
                World J Gastroenterol
                World J Gastroenterol
                WJG
                World Journal of Gastroenterology
                Baishideng Publishing Group Inc
                1007-9327
                2219-2840
                21 April 2023
                21 April 2023
                : 29
                : 15
                : 2241-2260
                Affiliations
                Human Genetics Unit, Indian Statistical Institute, Kolkata 700108, India
                Department of Molecular Biosciences, SVYASA School of Yoga and Naturopathy, Bangalore 560105, India
                Department of Pathology, Tata Medical Center, Kolkata 700160, India
                Department of General Surgery, IPGMER & SSKM Hospital, Kolkata 700020, India
                Department of Biochemistry, Royal Global University, Assam 781035, India
                Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9061, New Zealand
                School of Health Sciences and Technology, University of Petroleum and Energy Studies, Dehradun 248007, India
                Human Genetics Unit, Indian Statistical Institute, Kolkata 700108, India. snilabja@ 123456isical.ac.in
                Author notes

                Author contributions: Bararia A and Chakraborty P wrote the first draft of the paper and constructed the flow chart and tables; Chatterjee A, Roy P, Chattopadhay B K, Das A and Sikdar N provided valuable input, suggestions, comments and guidance while writing the review manuscript and contributed to proofreading and editing; Sikdar N constructed, wrote, conceptualized, and edited the review manuscript.

                Supported by the Department of Biotechnology, Government of India Grant Sanction, Ramalingaswami Re-entry Fellowship, No. RLS/BT/Re-entry/05/2012.

                Corresponding author: Nilabja Sikdar, PhD, Research Scientist, Doctor, Human Genetics Unit, Indian Statistical Institute, 203, B.T. Road, Kolkata 700108, India. snilabja@ 123456isical.ac.in

                Article
                jWJG.v29.i15.pg2241
                10.3748/wjg.v29.i15.2241
                10134423
                37124888
                932f3325-4afc-4dab-9f0e-9d088e45ff88
                ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.

                This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.

                History
                : 28 November 2022
                : 2 February 2023
                : 15 March 2023
                Categories
                Review

                non-invasive biomarkers,cell free biomarkers,proteomic biomarkers,liquid biopsy-based diagnostics,pancreatic cancer biomarkers

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