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Colorectal Cancer (CRC): Investigating the Expression of the Suppressor of Fused (SuFu) Gene and Its Relationship with Several Inflammatory Blood-Based Biomarkers

Background: Suppressor of fused (SuFu) is a tumor-suppressor gene that regulates hedgehog signaling. Its involvement in some malignancies is broadly accepted. However, its association with colorectal cancer (CRC) pathogenesis is not clear. Likewise, no study has clearly associated blood-based inflam...

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Autores principales: Rather, Tahseen Bilal, Parveiz, Ishrat, Bhat, Gulzar A, Rashid, Gowhar, Akhtar, Kulsum, Haque, Rizwanul, Ola, Mohammad Shamsul, Ali, Mehboob, Wani, Rauf A, Khan, Ishrat Younas, Besina, Syed, Mudassar, Syed
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9953361/
https://www.ncbi.nlm.nih.gov/pubmed/36831076
http://dx.doi.org/10.3390/biomedicines11020540
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author Rather, Tahseen Bilal
Parveiz, Ishrat
Bhat, Gulzar A
Rashid, Gowhar
Akhtar, Kulsum
Haque, Rizwanul
Ola, Mohammad Shamsul
Ali, Mehboob
Wani, Rauf A
Khan, Ishrat Younas
Besina, Syed
Mudassar, Syed
author_facet Rather, Tahseen Bilal
Parveiz, Ishrat
Bhat, Gulzar A
Rashid, Gowhar
Akhtar, Kulsum
Haque, Rizwanul
Ola, Mohammad Shamsul
Ali, Mehboob
Wani, Rauf A
Khan, Ishrat Younas
Besina, Syed
Mudassar, Syed
author_sort Rather, Tahseen Bilal
collection PubMed
description Background: Suppressor of fused (SuFu) is a tumor-suppressor gene that regulates hedgehog signaling. Its involvement in some malignancies is broadly accepted. However, its association with colorectal cancer (CRC) pathogenesis is not clear. Likewise, no study has clearly associated blood-based inflammatory biomarkers with cancer diagnosis/prognosis as yet. Aim: Our goal was to look at SuFu expression levels in CRC patients and its relationship with other clinicopathological factors. Additionally, we looked into the function of a few blood-based biomarkers in CRC and whether or not a combined strategy at the genetic and clinical levels can be applied in CRC. Methods: The investigation included 98 histopathologically confirmed CRC samples and adjacent normal tissues (controls). A colonoscopy was followed by a targeted biopsy for each suspected colon cancer patient. A CT scan and MRI were also performed on every patient with rectal cancer. Real-time polymerase chain reaction and immunohistochemistry (IHC) were used for assessment. A Beckman Coulter DxH900 was used to examine blood parameters. A Beckman Coulter DxI800 was used to identify pretreatment carcinoma embryonic antigens (CEA) and carbohydrate antigens (CA 19–9) in CRC patients. Results: The expression of SuFu was associated with gender, education, passive smoking, tumor grade, perineural invasion (PNI), lymph node metastasis (LNM), node status, stage, vital status, and recurrence (p < 0.05). In the combined analysis, the areas under the curve produced by the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and red cell distribution width (RDW) were the greatest (AUC(RDW+PLR+NLR) = 0.91, 95% CI: 0.86–0.93, p < 0.05). Furthermore, the most severe pathological features were linked to RDW, PLR, NLR, and HPR. SuFu expression, node status, LNM, PNI, and stage all had significant correlations with OS and DFS rates in IHC-based univariate survival analysis (p < 0.05). According to the Cox regression, CA-19.9 had a strong independent predictive link with 3-year DFS (p < 0.05). Conclusion: In CRC, SuFu was downregulated both transcriptionally and translationally, was primarily nucleo-cytoplasmic, and was expressed less in high-grade tumors. In addition, SuFu was linked to a poor overall and disease-free survival rate. It may be possible to use SuFu as a therapeutic target for CRC in the future. However, SuFu expression had no effect on RDW, PLR, NLR, or HPR serum levels.
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spelling pubmed-99533612023-02-25 Colorectal Cancer (CRC): Investigating the Expression of the Suppressor of Fused (SuFu) Gene and Its Relationship with Several Inflammatory Blood-Based Biomarkers Rather, Tahseen Bilal Parveiz, Ishrat Bhat, Gulzar A Rashid, Gowhar Akhtar, Kulsum Haque, Rizwanul Ola, Mohammad Shamsul Ali, Mehboob Wani, Rauf A Khan, Ishrat Younas Besina, Syed Mudassar, Syed Biomedicines Article Background: Suppressor of fused (SuFu) is a tumor-suppressor gene that regulates hedgehog signaling. Its involvement in some malignancies is broadly accepted. However, its association with colorectal cancer (CRC) pathogenesis is not clear. Likewise, no study has clearly associated blood-based inflammatory biomarkers with cancer diagnosis/prognosis as yet. Aim: Our goal was to look at SuFu expression levels in CRC patients and its relationship with other clinicopathological factors. Additionally, we looked into the function of a few blood-based biomarkers in CRC and whether or not a combined strategy at the genetic and clinical levels can be applied in CRC. Methods: The investigation included 98 histopathologically confirmed CRC samples and adjacent normal tissues (controls). A colonoscopy was followed by a targeted biopsy for each suspected colon cancer patient. A CT scan and MRI were also performed on every patient with rectal cancer. Real-time polymerase chain reaction and immunohistochemistry (IHC) were used for assessment. A Beckman Coulter DxH900 was used to examine blood parameters. A Beckman Coulter DxI800 was used to identify pretreatment carcinoma embryonic antigens (CEA) and carbohydrate antigens (CA 19–9) in CRC patients. Results: The expression of SuFu was associated with gender, education, passive smoking, tumor grade, perineural invasion (PNI), lymph node metastasis (LNM), node status, stage, vital status, and recurrence (p < 0.05). In the combined analysis, the areas under the curve produced by the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and red cell distribution width (RDW) were the greatest (AUC(RDW+PLR+NLR) = 0.91, 95% CI: 0.86–0.93, p < 0.05). Furthermore, the most severe pathological features were linked to RDW, PLR, NLR, and HPR. SuFu expression, node status, LNM, PNI, and stage all had significant correlations with OS and DFS rates in IHC-based univariate survival analysis (p < 0.05). According to the Cox regression, CA-19.9 had a strong independent predictive link with 3-year DFS (p < 0.05). Conclusion: In CRC, SuFu was downregulated both transcriptionally and translationally, was primarily nucleo-cytoplasmic, and was expressed less in high-grade tumors. In addition, SuFu was linked to a poor overall and disease-free survival rate. It may be possible to use SuFu as a therapeutic target for CRC in the future. However, SuFu expression had no effect on RDW, PLR, NLR, or HPR serum levels. MDPI 2023-02-13 /pmc/articles/PMC9953361/ /pubmed/36831076 http://dx.doi.org/10.3390/biomedicines11020540 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Rather, Tahseen Bilal
Parveiz, Ishrat
Bhat, Gulzar A
Rashid, Gowhar
Akhtar, Kulsum
Haque, Rizwanul
Ola, Mohammad Shamsul
Ali, Mehboob
Wani, Rauf A
Khan, Ishrat Younas
Besina, Syed
Mudassar, Syed
Colorectal Cancer (CRC): Investigating the Expression of the Suppressor of Fused (SuFu) Gene and Its Relationship with Several Inflammatory Blood-Based Biomarkers
title Colorectal Cancer (CRC): Investigating the Expression of the Suppressor of Fused (SuFu) Gene and Its Relationship with Several Inflammatory Blood-Based Biomarkers
title_full Colorectal Cancer (CRC): Investigating the Expression of the Suppressor of Fused (SuFu) Gene and Its Relationship with Several Inflammatory Blood-Based Biomarkers
title_fullStr Colorectal Cancer (CRC): Investigating the Expression of the Suppressor of Fused (SuFu) Gene and Its Relationship with Several Inflammatory Blood-Based Biomarkers
title_full_unstemmed Colorectal Cancer (CRC): Investigating the Expression of the Suppressor of Fused (SuFu) Gene and Its Relationship with Several Inflammatory Blood-Based Biomarkers
title_short Colorectal Cancer (CRC): Investigating the Expression of the Suppressor of Fused (SuFu) Gene and Its Relationship with Several Inflammatory Blood-Based Biomarkers
title_sort colorectal cancer (crc): investigating the expression of the suppressor of fused (sufu) gene and its relationship with several inflammatory blood-based biomarkers
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9953361/
https://www.ncbi.nlm.nih.gov/pubmed/36831076
http://dx.doi.org/10.3390/biomedicines11020540
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