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

Author:

Rather Tahseen Bilal1,Parveiz Ishrat1,Bhat Gulzar A2,Rashid Gowhar3,Akhtar Kulsum1,Haque Rizwanul4,Ola Mohammad Shamsul5ORCID,Ali Mehboob6,Wani Rauf A7ORCID,Khan Ishrat Younas8,Besina Syed8,Mudassar Syed1

Affiliation:

1. Department of Clinical Biochemistry, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar 190011, India

2. Scientist Multidisciplinary Research Unit, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar 190011, India

3. Department of Amity Medical School, Amity University Haryana, Haryana 125001, India

4. Department of Biotechnology, SEBES, Central University of South Bihar (Gaya), Bihar 824236, India

5. Department of Biochemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia

6. Senior Scientist Toxicology Invivotek Nexus, a Genesis Biotech Group LLC Company, 17 Black Forest RD, Hamilton, NJ 08690, USA

7. Department of General Surgery, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar 190011, India

8. Department of Pathology, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar 190011, India

Abstract

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 (AUCRDW+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.

Funder

Sher-I-Kashmir Institute of Medical Sciences, Kashmir, India

Publisher

MDPI AG

Subject

General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)

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