Clinicopathological characteristics of SMAD4 gene expressions in colorectal cancer patients.

Colorectal cancer (CRC) ranks as the third leading cause of cancer-related deaths globally. SMAD4 gene acts as the central mediator of the signaling pathway for transforming growth factor-ß (TGFß) with a significant effect on colorectal cancer. Previous research has confirmed a relationship between the presence of the SMAD4 gene and the survival and progression of colorectal cancer in patients. In this study, our goal was to analyze the presence of SMAD4 in both colorectal cancer and nearby normal tissues. The expression levels of SMAD4 were evaluated in 45 colorectal tumor tissues and 45 adjacent control tissues using the Quantitative Real-Time PCR (qRT-PCR) method. Additionally, we assessed the diagnostic effectiveness of SMAD4 by creating a receiver operating characteristic (ROC) curve. Our findings showed that the expression of SMAD4 was significantly reduced in colorectal cancer patients compared to the adjacent control group sample. Examination of clinicopathological characteristics of patients revealed varied correlations between SMAD4 gene expressions and TMN stage (p<0.0001). These findings suggest that SMAD4 levels could be used as possible diagnostic indicators for colorectal cancer.

The Relationship Between Serum IgE Level and IL-4 and IL-13 Cytokines in Colorectal Cancer Patients.

BACKGROUND: Colorectal cancer (CRC) is the most common malignancy of the digestive system in the world. Immune cells and molecules in tumor microenvironment are crucial.Identifying immune system components in cancer aids in biomarker discovery. This study investigated the serum IgE levels and expression of IL-4 and IL-13 in the tissue and serum of CRC patients and explored their possible association with pathological and clinical factors. MATERIALS AND METHODS: Thirty-six patients with CRC and 36 healthy individuals were involved in the study. Tissues and blood samples were collected. Serum levels of IgE and IL-4 and IL-13 were analyzed using the ELISA method. The quantitative Real-Time PCR (qRT-PCR) technique was used to assess the expression levels of the cytokines in CRC tissue samples in comparison with the adjacent control tissue. RESULTS: Our results revealed that the serum level of IL-4 and IL-13 and also their gene expression levels were significantly decreased in CRC patients compared to the controls. The results of this study revealed that there is no significant difference in the serum levels of IgE between CRC patients and the control group. CONCLUSION: All in all, the results of the current research suggest that the expression levels of IL-13, IL-4, and IgE vary between CRC tissue.

TNF-α, and TNFRs in gastrointestinal cancers.

Tumor necrosis factor-alpha (TNF-α) is a multifunctional cytokine that plays a role in the hemostasis of the immune system, inflammation, and cell proliferation. However, it can also have a dark side as it is involved in pro-inflammatory cytokines and pathological processes such as cell growth and death, autoimmunity, and inflammation, leading to a wide range of chronic inflammatory diseases, including digestive cancer. TNF-alpha binds to two distinct receptors, TNFRI and TNFRII. Upon binding of the ligand to these receptors, TNF receptor-associated factors (TRAFs) are recruited to the cytoplasmic receptor, triggering the activation of transcription factors such as NF-kB and Activator protein 1 (AP_1). In contrast, binding of cytokines to certain family members, such as TNF RI and Fas Ligand (Fas L), leads to the secretion and initiation of apoptosis. Gastrointestinal malignancies are among the most common types of cancer globally. Despite extensive research, the exact cause of these tumors remains a mystery. Unfortunately, they often have a poor prognosis and are often detected at a late stage. The global incidence of gastrointestinal cancers, including those of the stomach, esophagus, colon, liver, and pancreas, is on the rise, leading to a surge in both incidence and mortality. Growth factors and cytokines, which are signaling molecules found in the tumor microenvironment, are thought to be major contributors to the development and metastasis of these cancers. In this review, we explored the role of TNF-α, and its receptors in the development of digestive cancers, including its signaling pathways and functions.

The Relationship Between Serum and Tissue Levels of IL-13 and TYK2 in Colorectal Cancer Patients.

INTRODUCTION: Colorectal cancer (CRC) is a third  cause of death worldwide. The immune system plays a significant role in the tumor microenvironment and identifying its components involved in cancer development can aid in finding new biomarkers for prognosis, treatment monitoring, and immune-based therapies. Interleukin 13 (IL-13) is a cytokine produced by immune cells that has been implicated in tumor invasion, proliferation, and metastasis. Previous studies have shown that IL-13 causes the phosphorylation of Tyrosine kinase 2 (TYK2), which may contribute to the development and progression of cancer. This study investigated the levels expression of IL-13 and TYK2 in the tissue and serum of CRC patients and explored their possible association with pathological and clinical factors. METHODS: 105 patients with CRC and 105 healthy individuals were involved in the study. Tissue and blood samples were collected. The quantitative Real-Time PCR (qRT-PCR) technique was used to assess the expression levels of the IL-13 and TYK2 CRC tissue samples in comparison with the adjacent control tissue. RESULT: The expression levels of IL-13 were lower and TYK2 were found to be higher in CRC tissue compared to normal tissue. Additionally, serum levels of IL-13 were decreased in CRC patients while TYK2 levels were elevated. A significant negative correlation was found between the expression levels of IL-13 in both serum and tissue and the cancer stage. CONCLUSION: These results suggest that IL-13 and TYKMay 2 play essential roles in CRC development and progression and may serve as potential biomarkers for early detection and treatment.

Investigation of GNB1 derivative circular RNAs hsa_circ_0009361 and hsa_circ_0009362 expressions in colorectal cancer patients: potential new diagnostic factors.

Aim: We aim to investigate the relationship between hsa_circ_0009361 plus hsa_circ_0009362 expression levels and the clinicopathological features of colorectal cancer (CRC) patients. Background: Circular RNAs (circRNAs) are implicated in the progression and development of CRC. CircRNAs have been recognized as diagnostic and prognostic biomarkers, opening up a new window to comprehend the molecular basis of CRC. Given the significance of circRNAs and the G protein subunit b1 (GNB1) gene in malignancies, the goal of the current investigation was to determine the expression levels of GNB1 derivative circular RNAs circGNB1 (hsa_circ_0009361 and hsa_circ_0009362) in CRC and adjacent control tissues. Methods: The expression levels of the GNB1 derivative circular RNAs (hsa_circ_0009361 and hsa_circ_0009362) were evaluated using the quantitative real-time PCR (qRT-PCR) method in 45 CRC tissues and adjacent control tissues. Furthermore, we analyzed the diagnostic power of the mentioned circRNAs by plotting the receiver operating characteristic (ROC) curve. The association between the expression levels of hsa_circ_0009361 and hsa_circ_0009362 was evaluated using correlation analysis. Results: Our results revealed that the expression levels of hsa_circ_0009361 and hsa_circ_0009362 were significantly down-regulated in CRC tissues compared to the adjacent control group. Analysis of patients' clinicopathological features indicated that expressions of hsa_circ_0009361 and hsa_circ_0009362 were differently related to lymph vascular invasion (P<0.001). ROC curve results showed that these circRNAs are good candidate diagnostic biomarkers in CRCs. Pearson's correlation test revealed a positive correlation between hsa_circ_0009361 and hsa_circ_0009362 expression levels (P<0.0001). Conclusion: These results demonstrated that hsa_circ_0009361 and hsa_circ_0009362 expression levels may be used as possible diagnostic biomarkers for CRC.

The role of interferon-gamma and its receptors in gastrointestinal cancers.

Gastrointestinal malignancies are the most prevalent type of cancer around the world. Even though numerous studies have evaluated gastrointestinal malignancies, the actual underlying mechanism is still unknown. These tumors have a poor prognosis and are frequently discovered at an advanced stage. Globally, there is an increase in the incidence and mortality of gastrointestinal malignancies, including those of the stomach, esophagus, colon, liver, and pancreas. Growth factors and cytokines are signaling molecules that are part of the tumor microenvironment and play a significant role in the development and spread of malignancies. IFN-γ induce its effects by activation of intracellular molecular networks. The main pathway involved in IFN-γ signaling is the JAK/STAT pathway, which regulates the transcription of hundreds of genes and mediates various biological responses. IFN-γ receptor is composed of two IFN-γR1 chains and two IFN-γR2 chains. Binding to IFN-γ, causes the intracellular domains of IFN-γR2 to oligomerize and transphosphorylate with IFN-γR1 which activates downstream signaling components: JAK1 and JAK2. These activated JAKs phosphorylate the receptor, creating binding sites for STAT1. STAT1 is then phosphorylated by JAK, resulting in the formation of STAT1 homodimers (gamma activated factors or GAFs) that translocate to the nucleus and regulate gene expression. The balance between positive and negative regulation of this pathway is crucial for immune responses and tumorigenesis. In this paper, we evaluate the dynamic roles of IFN- γ and its receptors in gastrointestinal cancers and present evidence that inhibiting IFN- γ signaling may be an effective treatment strategy.

Molecular Characteristics of TYK2 Gene Expressions in Patients with Colorectal Cancer.

Background: TYK2 is a member of the JAK family and is known to mediate signals of multiple cytokines that play a crucial role in immune and inflammatory signaling. Activation of TYK2 in tumor cells has been linked to promote cell survival, growth, and invasion. This study aimed to investigate the expression of tyrosine kinase 2 (TYK2) in colorectal cancer (CRC) and adjacent control tissues. Materials and Methods: Quantitative Real-Time PCR (qRT-PCR) method was elaborated to examine the expression levels of TYK2 in 100 colorectal tumor tissues and adjacent tissues as a control. Furthermore, we analyzed the diagnostic power of the mentioned TYK2 by plotting the receiver operating characteristic (ROC) curve. Results: Our results revealed that the expression level of TYK2 was significantly up-regulated in CRC patients sample compared to the adjacent sample of the control group. Analysis of patient's clinic pathological features shows that expressions TYK2 were differently associated with lymph vascular invasion and TMN stage (P < 0.0001, P < 0.0006). Conclusion: These results indicated that TYK2 levels potential biomarkers for diagnosing colorectal cancer may be identified.