Department of Clinical Biochemistry, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, 190011, India.
Department of Medical Lab Technology, Amity Medical School Haryana, Amity University Haryana, Gurgaon, 125001, India.
J Gastrointest Cancer. 2024 Sep;55(3):1359-1379. doi: 10.1007/s12029-024-01090-y. Epub 2024 Jul 17.
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.
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.
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.
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.
Glioma-associated oncogene homolog-1（GLI1）在人类脑胶质瘤中扩增，越来越多的证据表明其在肿瘤发生和转移中具有重要作用。我们的目的是研究 GLI-1 基因在结直肠癌（CRC）进展中的作用及其与各种临床病理特征的相关性。此外，我们还研究了 GLI-1 基因和其他因素对 CRC 预后的影响。
我们分析了 98 例确诊的 CRC 病例和相邻正常组织对照。怀疑患有结肠癌的患者接受结肠镜检查和靶向活检，而患有直肠癌的患者接受 CT 扫描和 MRI。使用实时 PCR 检测、Western blot 和免疫组织化学检测 GLI1 表达。
在蛋白质和 mRNA 水平上，均观察到肿瘤组织中 GLI1 基因过度表达（p<0.05）。此外，GLI1 过表达与肿瘤浸润（T3/T4）、淋巴结存在、淋巴结转移（LNM）、分期（III/IV）、肿瘤部位（结肠）、肿瘤大小（≥3cm）、定位（核质）、强染色强度和复发等多种因素显著相关（p<0.05）。生存分析结果表明，GLI1 过表达的患者 DFS 率明显较低（21 个月），而表达正常的患者 DFS 率较高（31 个月）（p<0.05）。此外，与核质定位的 GLI1 相比，早期发病（15 个月）患者的 GLI1 基因更易发生细胞质定位，而核质定位的 GLI1 表现为晚期发病（23 个月）（p<0.05）。最后，根据 Cox 回归分析发现，分期和 PNI（p<0.05）是影响 CRC 患者预后的独立因素。
CRC 中 GLI-1 的高表达与不良病理和患者预后不良有关。GLI-1 细胞质定位与无病生存时间缩短之间的相关性可能有助于指导预后和治疗。需要进一步研究以开发针对 GLI-1 的治疗策略，以改善预后。
