GLI1 Subcellular Localization and Overexpression as Prognostic Factors for Disease-Free Survival in Colorectal Carcinoma

• Published in: Journal of gastrointestinal cancer Vol. 55; no. 3; pp. 1359 - 1379
• Main Authors: Rather, Tahseen Bilal, Parveiz, Ishrat, Rashid, Gowhar, Akhtar, Kulsum, Mudassar, Syed, wani, Rauf A., Besina, Syed, Haq, Rather izhar Ul
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.09.2024
• Subjects: Adult; Aged; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Cancer Research; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - mortality; Colorectal Neoplasms - pathology; Disease-Free Survival; Female; Gastroenterology; Gene Expression Regulation, Neoplastic; Humans; Internal Medicine; Lymphatic Metastasis; Male; Medicine; Medicine & Public Health; Middle Aged; Oncology; Prognosis; Radiotherapy; Zinc Finger Protein GLI1 - genetics; Zinc Finger Protein GLI1 - metabolism; Immunohistochemistry; Real-time PCR; CRC; Western blotting; Disease-free survival
• ISSN: 1941-6628; 1941-6636; 1941-6636
• DOI: 10.1007/s12029-024-01090-y

Purpose Glioma-associated oncogene homolog-1 (GLI1) is amplified in human glioblastoma, and there is growing evidence suggesting its significant role in tumor development and metastasis. Our aim was to investigate the role of the GLI-1 gene in the progression of colorectal cancer (CRC) and its correlation with various clinicopathological features. Additionally, we examined the impact of the GLI-1 gene and other factors on the prognosis of CRC. Methods We analyzed a total of 98 confirmed CRC cases and adjacent normal tissue controls. Patients suspected of having colon cancer underwent a colonoscopy and targeted biopsy, while those with rectal cancer underwent CT scans and MRI. GLI1 expression was detected using real-time PCR assay, Western blotting, and immunohistochemistry. Results The GLI1 gene was observed to be overexpressed in tumor tissues at both the protein and mRNA levels ( p  < 0.05). In addition, GLI1 overexpression was significantly associated with various factors such as tumor invasion (T3/T4), presence of lymph nodes, lymph node metastasis (LNM), stage (III/IV), tumor site (colon), tumor size (≥ 3 cm), localization (nucleocytoplasmic), strong staining intensity and recurrence ( p  < 0.05). The results of survival analysis showed that the patients with overexpression of GLI1 had a significantly lower DFS rate which was 21 months compared to those with normal expression who had 31 months ( p  < 0.05). Moreover, individuals with early onset disease (15 months) were more likely to have cytoplasmic localization of the GLI1 gene as opposed to nucleo-cytoplasmic localization of GLI1 which presented late-onset disease( 23 months) ( p  < 0.05). Finally, Stage and PNI ( p  < 0.05) were found to independently affect outcomes of CRC according to Cox regression analysis. Conclusion High expression of GLI-1 in CRC is associated with adverse pathology and poor prognosis for patients. The correlation between cytoplasmic localization of GLI-1 and reduced disease-free survival holds potential for guiding prognosis and treatment. Further research is needed to develop strategies targeting GLI-1 for improved outcomes.