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      Prognostic and clinic-pathological significances of HOXB8, ILK and FAT4 expression in colorectal cancer

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          Abstract

          Introduction

          HOXB8 is a protein that was found to promote cancer proliferation and invasion. ILK is a protein kinase which has a role in carcinogenesis. FAT4 is a tumor homologue that has a role in EMT and autophagy regulation.

          Aim of the study

          To identify expression of Human HOXB8, Integrin-linked kinase (ILK1) and FAT homolog 4 (FAT4) in colorectal cancer (CRC) correlating their expression with pathological, prognostic and clinical parameters of CRC.

          Material and methods

          We assessed the expression of HOXB8, ILK and FAT4 in fifty CRC patients and ten samples from nearby non-neoplastic colonic mucosa using immunohistochemistry.

          Results

          The expression of HOXB8 and ILK in CRC was positively associated with high tumor grade, advanced tumor stage, lymph node involvement ( p < 0.001), occurrence of distant metastases ( p = 0.003 and 0.024 respectively), higher incidence of tumor recurrence ( p = 0.03, p < 0.001 respectively), worse survival rates ( p = 0.038 and 0.003 respectively). The expression of FAT4 in CRC was correlated with lower grade, early stage of the tumor, absence of lymph node involvement ( p < 0.001) and lack of distant metastases ( p = 0.011). High FAT4 expression was associated with absence of tumor recurrence ( p < 0.001) and favorable survival rates ( p < 0.001 and 0.003).

          Conclusions

          High immunohistochemical expression of HOXB8 and ILK in addition to low immunohistochemical expression of FAT4 was associated with unfavorable prognostic and pathological parameters of CRC.

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          Most cited references36

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          Colorectal cancer statistics, 2017.

          Colorectal cancer (CRC) is one of the most common malignancies in the United States. Every 3 years, the American Cancer Society provides an update of CRC incidence, survival, and mortality rates and trends. Incidence data through 2013 were provided 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 2014 were provided by the National Center for Health Statistics. CRC incidence rates are highest in Alaska Natives and blacks and lowest in Asian/Pacific Islanders, and they are 30% to 40% higher in men than in women. Recent temporal patterns are generally similar by race and sex, but differ by age. Between 2000 and 2013, incidence rates in adults aged ≥50 years declined by 32%, with the drop largest for distal tumors in people aged ≥65 years (incidence rate ratio [IRR], 0.50; 95% confidence interval [95% CI], 0.48-0.52) and smallest for rectal tumors in ages 50 to 64 years (male IRR, 0.91; 95% CI, 0.85-0.96; female IRR, 1.00; 95% CI, 0.93-1.08). Overall CRC incidence in individuals ages ≥50 years declined from 2009 to 2013 in every state except Arkansas, with the decrease exceeding 5% annually in 7 states; however, rectal tumor incidence in those ages 50 to 64 years was stable in most states. Among adults aged <50 years, CRC incidence rates increased by 22% from 2000 to 2013, driven solely by tumors in the distal colon (IRR, 1.24; 95% CI, 1.13-1.35) and rectum (IRR, 1.22; 95% CI, 1.13-1.31). Similar to incidence patterns, CRC death rates decreased by 34% among individuals aged ≥50 years during 2000 through 2014, but increased by 13% in those aged <50 years. Progress against CRC can be accelerated by increasing initiation of screening at age 50 years (average risk) or earlier (eg, family history of CRC/advanced adenomas) and eliminating disparities in high-quality treatment. In addition, research is needed to elucidate causes for increasing CRC in young adults. CA Cancer J Clin 2017. © 2017 American Cancer Society. CA Cancer J Clin 2017;67:177-193. © 2017 American Cancer Society.
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            ESMO consensus guidelines for the management of patients with metastatic colorectal cancer.

            Colorectal cancer (CRC) is one of the most common malignancies in Western countries. Over the last 20 years, and the last decade in particular, the clinical outcome for patients with metastatic CRC (mCRC) has improved greatly due not only to an increase in the number of patients being referred for and undergoing surgical resection of their localised metastatic disease but also to a more strategic approach to the delivery of systemic therapy and an expansion in the use of ablative techniques. This reflects the increase in the number of patients that are being managed within a multidisciplinary team environment and specialist cancer centres, and the emergence over the same time period not only of improved imaging techniques but also prognostic and predictive molecular markers. Treatment decisions for patients with mCRC must be evidence-based. Thus, these ESMO consensus guidelines have been developed based on the current available evidence to provide a series of evidence-based recommendations to assist in the treatment and management of patients with mCRC in this rapidly evolving treatment setting.
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              Autophagy and the integrated stress response.

              Autophagy is a tightly regulated pathway involving the lysosomal degradation of cytoplasmic organelles or cytosolic components. This pathway can be stimulated by multiple forms of cellular stress, including nutrient or growth factor deprivation, hypoxia, reactive oxygen species, DNA damage, protein aggregates, damaged organelles, or intracellular pathogens. Both specific, stimulus-dependent and more general, stimulus-independent signaling pathways are activated to coordinate different phases of autophagy. Autophagy can be integrated with other cellular stress responses through parallel stimulation of autophagy and other stress responses by specific stress stimuli, through dual regulation of autophagy and other stress responses by multifunctional stress signaling molecules, and/or through mutual control of autophagy and other stress responses. Thus, autophagy is a cell biological process that is a central component of the integrated stress response. Copyright © 2010 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Contemp Oncol (Pozn)
                Contemp Oncol (Pozn)
                WO
                Contemporary Oncology
                Termedia Publishing House
                1428-2526
                1897-4309
                30 October 2020
                2020
                : 24
                : 3
                : 183-192
                Affiliations
                [1 ]Department of Basic Medical Sciences, College of Medicine, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia
                [2 ]Department of Pathology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
                [3 ]Department of General Surgery, Faculty of Medicine, Zagazig University, Zagazig, Egypt
                Author notes
                Address for correspondence: Ola A. Harb Department of Pathology, Faculty of Medicine, Zagazig University, 11111 Zagazig, Egypt e-mail: olaharb2015@ 123456gmail.com
                Article
                42198
                10.5114/wo.2020.100281
                7670183
                33235545
                448e7fd7-971c-4705-9448-cdcb146568d6
                Copyright © 2020 Termedia

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0). License ( http://creativecommons.org/licenses/by-nc-sa/4.0/)

                History
                : 08 August 2020
                : 11 October 2020
                Categories
                Original Paper

                hoxb8,ilk and fat4,colorectal cancer,recurrence,survival
                hoxb8, ilk and fat4, colorectal cancer, recurrence, survival

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