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.PURPOSEGlioma-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.METHODSWe 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.RESULTSThe 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.CONCLUSIONHigh 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.
Background: Past research has demonstrated that a changed Sonic Hedgehog (SHH) pattern contributes to the development of colorectal cancer. This study’s objective was to determine whether the SHH ...gene’s promoter hypomethylation might be used to predict the likelihood of developing colorectal cancer.
Methods: For the current investigation, 50 newly diagnosed and untreated colorectal cancer patients’ tumor samples and surrounding non-tumor tissues were gathered. SHH methylation was determined by methylation-specific PCR (MSP) and results correlated with several studied clinicopathological parameters.
Results: Our results showed that SHH methylation levels are significantly present in normal tissues as compared to tumor tissues.
Conclusion: We conclude SHH promoter is hypomethylated in colorectal cancers which may have an effect driving normal colon and rectum cells to cancer.
Bangladesh Journal of Medical Science Vol. 23 No. 01 January’24 Page : 200-206
Smoothened (SMO) is a significant signalling protein which functions as a key transducer for the hedgehog signalling pathway, an important signalling mechanism with key roles in development and ...oncogenesis. The correlation of expression dynamics of SMO with pancreatic and colorectal cancer genesis has been known but with ambiguity. Therefore, in this study, we investigated messenger RNA (mRNA) and protein expression of SMO in pancreatic and colorectal cancers in our population and assessed relationship with various clinicopathological parameters. Surgically resected tumour and adjacent histologically normal tissues from 33 and 61 pancreatic and colorectal cancer patients were investigated in the present study. Expression of SMO was analysed by quantitative real‐time polymerase chain reaction and immunohistochemistry. At mRNA level, SMO was overexpressed in 72.72% (24 of 33) and 50.81% (31 of 61) of the pancreatic and colorectal cancer cases as compared with their adjacent normal tissues. SMO immunohistochemical analysis revealed nuclear localization and overexpression was observed in 51.51% (17 of 33) and 40.98% (25 of 61) of pancreatic and colorectal cancer tissues. SMO overexpression was significantly associated with smoking, late‐stage disease and lymph node metastasis in patients with Colorectal cancer. Our results showed that SMO is dysregulated in pancreatic and colorectal cancers and may be considered as a target in cancer therapeutics.
Smoothened (SMO) has key roles in development and oncogenesis. SMO is dysregulated in pancreatic and colorectal cancers and may be considered as a target in cancer therapeutics.
Background: Neoadjuvant chemoradiotherapy (NACRT) is an established treatment option for locally advanced rectal cancer (LARC). Patients achieving pathological complete response (pCR) following NACRT ...have better oncological outcomes and may be subjected to wait and watch policy as well. The aim of this study was to identify predictors of pCR in LARC following NACRT.
Materials and Methods: A retrospective analysis of a prospectively maintained colorectal cancer database from January 2018 to December 2019 was undertaken. A total of 129 patients of LARC who were subjected to conventional long course NACRT, followed by surgery were included in the study. Pathological response to NACRT was assessed using Mandard grading system and response was categorized as pCR or not-pCR. Correlation between various clinico pathological parameters and pCR was determined using univariate and multivariate logistic regression analysis.
Results: Mean age of patients was 53.79 ± 1.303 years. Complete pathological response (Mandard Gr 1) was achieved in 24/129 (18.6%) patients. Age of patients more than 60 years (P = 0.011; odds ratio OR 3.194, 95% confidence interval CI 1.274-8.011), interval between last dose of NACRT and surgery >8 weeks (P = 0.004; OR 4.833, 95% CI 1.874-12.467), well-differentiated tumors (P < 0.0001; OR 32.00, 95% CI 10.14-100.97) and node-negative disease (P = 0.003; OR 111.0, 95% CI 2.51-48.03) proved to be strong predictors of pCR.
Conclusion: Older age, longer interval between NACRT and surgery, node-negative disease and favorable tumor grade help in achieving better pCR rates. Awareness of these variables can be valuable in counseling patients regarding prognosis and treatment options.
Sonic hedgehog (SHH) is a secreted protein which functions in autocrine or paracrine fashion on target cells to activate hedgehog (HH) signalling cascade responsible for growth and proliferation. ...This study is an attempt to understand the expression dynamics of SHH protein in colon, rectal and pancreatic cancers. Protein expression of SHH was studied by Western Blotting in the histologically confirmed colon, rectum and pancreatic cancer tissue samples along with their adjacent normal tissues. Only 31.4% (11 of 35) and 26.9% (7 of 26) of colon and rectal cancer cases respectively showed an increase in SHH expression in tumours compared to 72.7% (24 of 33) of the pancreatic cancer cases when compared with their adjacent normal tissues. Our results suggest that SHH may have a strong role in the predisposition of Pancreatic cancer and could possibly be used as a diagnostic or prognostic biomarker.
Forkhead Box M1 (FOXM1)—a key cell cycle regulator is a member of the Forkhead transcription factor family. It plays a key role in embryogenesis and cell proliferation and has been strongly linked to ...various solid tumors. We sought to understand the regulation of FOXM1 in colorectal cancer (CRC), as well as if and to what extent other clinicopathological characteristics are associated with FOXM1. The investigation comprised 98 CRC samples and normal tissues (controls). All colon cancer patients had a colonoscopy and targeted biopsy. All rectal cancer patients had a CT and MRI. Real-time PCR, Immunohistochemistry, and Western blotting were used to evaluate FOXM1 expression, and the findings were analyzed using SPSS (v.26). FOXM1 mRNA and protein expression were substantially upregulated in tumor tissues, with the majority of these proteins localized in nucleo-cytoplasm. Elevated protein levels of FOXM1 were strongly correlated with lower education level, larger tumor size, lymph node status, lymphovascular invasion (LVI), perineural invasion (PNI), lymph node metastasis (LNM), tumor invasion depth (subserosal and serosal invasion), late stage (III and IV), localization (nucleo-cytoplasmic), intensity (strong) and recurrence. Based on survival analysis, FOXM1 overexpression and nucleo-cytoplasmic localization were associated with shorter disease-free survival while stage and PNI were linked to poorer overall and disease-free survival. According to the results of the Cox regression analysis, stage and PNI were significant predictors of prognosis in CRC patients. FOXM1 expression was elevated in CRC and was linked to reduced disease-free survival. These findings support prior reports and hence FOXM1 can be an important prognostic marker for CRC and a promising therapeutic target. Additionally, we found a link between poor disease-free survival and FOXM1's nucleo-cytoplasmic localization. However, since the sample size of this study was small, further research is needed to validate our findings.
Abstract
Background
The diffusion-weighted imaging (DWI) is based on the random Brownian motion of water molecules that influences image contrast depending on different pathological conditions.
...Objective
The purpose of this study was to evaluate the efficacy of various magnetic resonance imaging (MRI) sequences including diffusion-weighted and gadobenate-enhanced MRI in the detection and characterization of liver lesions in a patient of known primary malignancy and to compare MRI with contrast-enhanced computed tomography (CECT) and ultrasonography (USG) in the detection of liver metastases.
Methods
All patients underwent a multiphase MRI. The final diagnosis was established by histopathological examination.
Results
A total of 43 patients of known primary malignancy were enrolled. MRI gave a provisional diagnosis of liver metastases in 21 patients and benign disease in 22 patients with histopathological correlation revealing two false-negative and one false-positive result. In the detection of lesions, DWI outscored other sequences (92.9 vs. 83.5% in hepatobiliary phase vs. 55.0% in T
2
-weighted sequences) with a statistically significant difference noted only in comparison with T
2
-weighted sequences (
p
< 0.001). In 16 patients, MRI added new lesions that were not detected by CECT/USG. The sensitivity and specificity of MRI for detecting metastases were 90.9%/95.2% and 97.9%/96.8% for per-patient and per-lesion basis, respectively.
Conclusion
Multiphase MRI improved both the detection and characterization of liver metastases. Adding DWI to the routine MR sequences helped in detecting small liver metastases (<10 mm) not detected by other sequences.
Suppressor of fused (
) 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.
Our goal was to look at
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.
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.
The expression of
was associated with gender, education, passive smoking, tumor grade, perineural invasion (PNI), lymph node metastasis (LNM), node status, stage, vital status, and recurrence (
< 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
= 0.91, 95% CI: 0.86-0.93,
< 0.05). Furthermore, the most severe pathological features were linked to RDW, PLR, NLR, and HPR.
expression, node status, LNM, PNI, and stage all had significant correlations with OS and DFS rates in IHC-based univariate survival analysis (
< 0.05). According to the Cox regression, CA-19.9 had a strong independent predictive link with 3-year DFS (
< 0.05).
In CRC,
was downregulated both transcriptionally and translationally, was primarily nucleo-cytoplasmic, and was expressed less in high-grade tumors. In addition,
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,
expression had no effect on RDW, PLR, NLR, or HPR serum levels.
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