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      Autophagy-associated HMGB-1 as a novel potential circulating non-invasive diagnostic marker for detection of Urothelial Carcinoma of Bladder

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          Abstract

          Urothelial carcinoma of bladder (UBC), a highly prevalent urological malignancy associated with high mortality and recurrence rate. Standard diagnostic method currently being used is cystoscopy but its invasive nature and low sensitivity stresses for identifying predictive diagnostic marker. Autophagy, a cellular homeostasis maintaining process, is usually dysregulated in cancer and its role is still enigmatic in UBC. In this study, 30 UBC patients and healthy controls were enrolled. Histopathologically confirmed tumor and adjacent normal tissue were acquired from patients. Molecular expression and tissue localization of autophagy-associated molecules (HMGB-1, RAGE, beclin, LC-3, and p62) were investigated. Serum HMGB-1 concentration was measured in UBC patients and healthy controls. ROC curves were plotted to evaluate diagnostic potential. Transcript, protein, and IHC expression of HMGB-1, RAGE, beclin, and LC-3 displayed upregulated expression, while p62 was downregulated in bladder tumor tissue. Serum HMGB-1 levels were elevated in UBC patients. Transcript and circulatory levels of HMGB-1 showed positive correlation and displayed a positive trend with disease severity. Upon comparison with clinicopathological parameters, HMGB-1 emerged as molecule of statistical significance to exhibit association. HMGB-1 exhibited optimum sensitivity and specificity in serum. The positive correlation between tissue and serum levels of HMGB-1 showcases serum as a representation of in situ scenario, suggesting its clinical applicability for non-invasive testing. Moreover, optimum sensitivity and specificity displayed by HMGB-1 along with significant association with clinicopathological parameters makes it a potential candidate to be used as diagnostic marker for early detection of UBC but requires further validation in larger cohort.

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s11010-021-04299-8.

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          Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

          Ahmedin Jemal, Lindsey A Torre, Rebecca Siegel … (2018)
          This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.
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            Autophagy: process and function.

            Noboru Mizushima (2007)
            Autophagy is an intracellular degradation system that delivers cytoplasmic constituents to the lysosome. Despite its simplicity, recent progress has demonstrated that autophagy plays a wide variety of physiological and pathophysiological roles, which are sometimes complex. Autophagy consists of several sequential steps--sequestration, transport to lysosomes, degradation, and utilization of degradation products--and each step may exert different function. In this review, the process of autophagy is summarized, and the role of autophagy is discussed in a process-based manner.
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              Bladder cancer.

              Ashish Kamat, Noah M Hahn, Jason Efstathiou … (2016)
              Bladder cancer is a complex disease associated with high morbidity and mortality rates if not treated optimally. Awareness of haematuria as the major presenting symptom is paramount, and early diagnosis with individualised treatment and follow-up is the key to a successful outcome. For non-muscle-invasive bladder cancer, the mainstay of treatment is complete resection of the tumour followed by induction and maintenance immunotherapy with intravesical BCG vaccine or intravesical chemotherapy. For muscle-invasive bladder cancer, multimodal treatment involving radical cystectomy with neoadjuvant chemotherapy offers the best chance for cure. Selected patients with muscle-invasive tumours can be offered bladder-sparing trimodality treatment consisting of transurethral resection with chemoradiation. Advanced disease is best treated with systemic cisplatin-based chemotherapy; immunotherapy is emerging as a viable salvage treatment for patients in whom first-line chemotherapy cannot control the disease. Developments in the past 2 years have shed light on genetic subtypes of bladder cancer that might differ from one another in response to various treatments.
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                Author and article information

                Contributors
                Alpana Sharma:
                ORCID: http://orcid.org/0000-0001-7633-9973
                dralpanasharma@gmail.com
                Journal
                Journal ID (nlm-ta): Mol Cell Biochem
                Journal ID (iso-abbrev): Mol Cell Biochem
                Title: Molecular and Cellular Biochemistry
                Publisher: Springer US (New York )
                ISSN (Print): 0300-8177
                ISSN (Electronic): 1573-4919
                Publication date (Electronic): 18 November 2021
                Pages: 1-13
                Affiliations
                [1 ]GRID grid.413618.9, ISNI 0000 0004 1767 6103, Department of Biochemistry, , All India Institute of Medical Sciences (AIIMS), ; New Delhi, India
                [2 ]GRID grid.413618.9, ISNI 0000 0004 1767 6103, Department of Pathology, , All India Institute of Medical Sciences (AIIMS), ; New Delhi, India
                [3 ]GRID grid.413618.9, ISNI 0000 0004 1767 6103, Department of Urology, , All India Institute of Medical Sciences (AIIMS), ; New Delhi, India
                [4 ]GRID grid.413618.9, ISNI 0000 0004 1767 6103, Department of Biostatistics, , All India Institute of Medical Sciences (AIIMS), ; New Delhi, India
                Author information
                http://orcid.org/0000-0001-7633-9973
                Article
                Publisher ID: 4299
                DOI: 10.1007/s11010-021-04299-8
                PMC ID: 8601373
                PubMed ID: 34796446
                SO-VID: 09f436ee-3787-41c0-b5b9-6349c6206d8c
                Copyright © © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021
                License:

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                Date received : 12 July 2021
                Date accepted : 4 November 2021
                Categories
                Subject: Article

                ScienceOpen disciplines: Biochemistry
                Keywords: bladder cancer,autophagy,hmgb-1,diagnostic marker
                Data availability:
                ScienceOpen disciplines: Biochemistry
                Keywords: bladder cancer, autophagy, hmgb-1, diagnostic marker

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