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      Molecular characteristics and prognostic significances of lysosomal-dependent cell death in kidney renal clear cell carcinoma

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          Abstract

          Lysosomal-dependent cell death (LDCD) has an excellent therapeutic effect on apoptosis-resistant and drug-resistant tumors; however, the important role of LDCD-related genes (LDCD-RGs) in kidney renal clear cell carcinoma (KIRC) has not been reported. Initially, single-cell atlas of LDCD signal in KIRC was comprehensively depicted. We also emphasized the molecular characteristics of LDCD-RGs in various human neoplasms. Predicated upon the expressive quotients of LDCD-RGs, we stratified KIRC patients into tripartite cohorts denoted as C1, C2, and C3. Those allocated to the ambit of C1 evinced the most sanguine prognosis within the KIRC cohort, underscored by the acme of LDCD-RGs scores. This further confirms the significant role that LDCD-RGs play in both the pathophysiological foundation and clinical implications of KIRC. In culmination, by virtue of employing the LASSO-Cox analytical modality, we have ushered in an innovative and avant-garde prognostic framework tailored for KIRC, predicated on the bedrock of LDCD-RGs. The assemblage of KIRC instances was arbitrarily apportioned into constituents inclusive of a didactic cohort, an internally wielded validation cadre, and an externally administered validation cohort. Concurrently, patients were dichotomized into strata connoting elevated jeopardy synonymous with adverse prognostic trajectories, and conversely, diminished risk tantamount to favorable prognoses, contingent on the calibrated expressions of LDCD-RGs. Succinctly, our investigative findings serve to underscore the cardinal capacity harbored by LDCD-RGs within the KIRC milieu, concurrently birthing a pioneering prognostic schema intrinsically linked to the trajectory of KIRC and its attendant prognoses.

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          Most cited references48

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          Hallmarks of Cancer: The Next Generation

          The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors. The hallmarks constitute an organizing principle for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Underlying these hallmarks are genome instability, which generates the genetic diversity that expedites their acquisition, and inflammation, which fosters multiple hallmark functions. Conceptual progress in the last decade has added two emerging hallmarks of potential generality to this list-reprogramming of energy metabolism and evading immune destruction. In addition to cancer cells, tumors exhibit another dimension of complexity: they contain a repertoire of recruited, ostensibly normal cells that contribute to the acquisition of hallmark traits by creating the "tumor microenvironment." Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer. Copyright © 2011 Elsevier Inc. All rights reserved.
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            Cancer statistics, 2019

            Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data, available through 2015, 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, available through 2016, were collected by the National Center for Health Statistics. In 2019, 1,762,450 new cancer cases and 606,880 cancer deaths are projected to occur in the United States. Over the past decade of data, the cancer incidence rate (2006-2015) was stable in women and declined by approximately 2% per year in men, whereas the cancer death rate (2007-2016) declined annually by 1.4% and 1.8%, respectively. The overall cancer death rate dropped continuously from 1991 to 2016 by a total of 27%, translating into approximately 2,629,200 fewer cancer deaths than would have been expected if death rates had remained at their peak. Although the racial gap in cancer mortality is slowly narrowing, socioeconomic inequalities are widening, with the most notable gaps for the most preventable cancers. For example, compared with the most affluent counties, mortality rates in the poorest counties were 2-fold higher for cervical cancer and 40% higher for male lung and liver cancers during 2012-2016. Some states are home to both the wealthiest and the poorest counties, suggesting the opportunity for more equitable dissemination of effective cancer prevention, early detection, and treatment strategies. A broader application of existing cancer control knowledge with an emphasis on disadvantaged groups would undoubtedly accelerate progress against cancer.
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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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                Author and article information

                Journal
                Aging (Albany NY)
                Aging
                Aging (Albany NY)
                Impact Journals
                1945-4589
                15 March 2024
                07 March 2024
                : 16
                : 5
                : 4862-4888
                Affiliations
                [1 ]Department of Urology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
                [2 ]Department of Dermatology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
                [3 ]Department of Urology, Central Hospital of Benxi, Benxi, Liaoning, China
                [4 ]Department of General Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
                [5 ]The Health Management Center, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
                Author notes
                [*]

                Equal contribution

                Correspondence to: Jianbo Wang; email: wangjianbo@dmu.edu.cn
                Correspondence to: Zhijun Hong; email: happyday246@163.com, https://orcid.org/0000-0002-7707-7570
                Correspondence to: Xu Chen; email: chenxdy@163.com, https://orcid.org/0000-0001-9681-1630
                Article
                205639 205639
                10.18632/aging.205639
                10968703
                38460947
                4a8d7ee8-0b16-4101-9a68-8f261e8062ec
                Copyright: © 2024 He et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 07 September 2023
                : 17 January 2024
                Categories
                Research Paper

                Cell biology
                kidney renal clear cell carcinoma,lysosomal-dependent cell death,molecular classification,prognosis significance,therapeutic opportunities

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