Overexpression of MISP is found in Gastric Cancer and Intestinal Metaplasia

Virlliano Thomas^*
*Correspondence: Virlliano Thomas, Department of Biology, University of Porto, Porto, Portugal, Email:

Keywords

Gastric cancer • MISP • Cancer patients

Introduction

MISP also known as C19 or f21 is a protein that plays a crucial role in the positioning of the mitotic spindle during cell division. The mitotic spindle is a structure composed of microtubules that segregates chromosomes into daughter cells. Proper spindle positioning ensures accurate chromosome segregation, which is vital for maintaining genomic integrity. MISP is localized to the spindle poles and interacts with other proteins involved in spindle dynamics and cell cortex positioning. It has been shown to be essential for the correct orientation of the mitotic spindle and the symmetric division of cells. Several studies have investigated the expression levels of MISP in gastric cancer tissues compared to normal gastric tissues. Using techniques such as quantitative PCR, Western blotting, and immunohistochemistry, researchers have consistently found that MISP is significantly overexpressed in gastric cancer samples. For instance, a study conducted by Zhang et al. (2020) reported that MISP mRNA levels were markedly higher in gastric cancer tissues than in adjacent normal tissues. This overexpression was correlated with poor prognosis, suggesting that MISP may serve as a prognostic biomarker for gastric cancer [1].

The mechanisms underlying MISP overexpression in gastric cancer are not fully understood, but several possibilities have been proposed. One potential mechanism is gene amplification, where multiple copies of the MISP gene are present in cancer cells, leading to increased mRNA and protein production. Another possibility is the upregulation of transcription factors that drive MISP expression. For example, the transcription factor E2F1, which is often deregulated in cancers, has been shown to bind to the promoter region of MISP and enhance its transcription. Additionally, epigenetic modifications such as DNA methylation and histone acetylation could also play a role in the dysregulation of MISP expression in gastric cancer. Intestinal metaplasia is a condition in which the gastric mucosa is replaced by intestinal-type epithelium. It is considered a precancerous lesion and a significant risk factor for the development of gastric cancer. The overexpression of MISP in intestinal metaplasia has also been reported, suggesting that MISP may play a role in the early stages of gastric carcinogenesis [2].

Literature Review

Studies examining clinical samples of intestinal metaplasia have found elevated levels of MISP compared to normal gastric tissues. Immunohistochemical analyses have demonstrated that MISP is overexpressed in the metaplastic cells, particularly in cases with a higher degree of dysplasia. This pattern of expression indicates that MISP may be involved in the transition from normal gastric epithelium to metaplastic and ultimately cancerous tissue. The mechanisms driving MISP overexpression in intestinal metaplasia are likely similar to those in gastric cancer. Chronic inflammation, a common feature of conditions leading to intestinal metaplasia, can result in increased cellular turnover and a higher likelihood of genetic and epigenetic alterations. These changes can activate pathways that upregulate MISP expression. For instance, chronic gastritis caused by Helicobacter pylori infection is a known precursor to intestinal metaplasia and has been associated with alterations in gene expression profiles, including genes involved in cell division and differentiation such as MISP.

The overexpression of MISP in gastric cancer and intestinal metaplasia presents an opportunity to develop new diagnostic tools. MISP could serve as a biomarker for the early detection of gastric cancer and its precursor lesions. Techniques such as immunohistochemistry and in situ hybridization could be used to detect MISP expression in biopsy samples, aiding in the identification of patients at high risk for developing gastric cancer. Additionally, circulating tumor cells or cell-free DNA in the blood could be analyzed for MISP expression, providing a non-invasive diagnostic option [3].

Discussion

Given its role in cell division and tumor progression, MISP represents a potential therapeutic target for gastric cancer. Inhibiting MISP function could disrupt mitotic spindle positioning, leading to cell cycle arrest and apoptosis in cancer cells. Small molecule inhibitors or monoclonal antibodies targeting MISP or its interacting partners could be developed as novel cancer therapies. Moreover, combination therapies involving MISP inhibitors and other anticancer agents may enhance treatment efficacy and overcome resistance mechanisms [4]. The correlation between MISP overexpression and poor prognosis in gastric cancer suggests that MISP could be used as a prognostic marker. Assessing MISP levels in tumor samples could help stratify patients based on their risk of disease progression and guide treatment decisions. Patients with high MISP expression may benefit from more aggressive treatment strategies, while those with lower expression could be spared from unnecessary side effects of intensive therapy.

While the current evidence supports the role of MISP in gastric cancer and intestinal metaplasia, further research is needed to fully elucidate its biological functions and regulatory mechanisms. Large-scale studies involving diverse patient populations are necessary to validate the diagnostic and prognostic utility of MISP. Additionally, functional studies using cell lines and animal models could provide insights into the precise role of MISP in tumorigenesis and identify potential therapeutic targets. To translate the findings from basic research into clinical practice, well-designed clinical trials are essential. Trials investigating the efficacy and safety of MISP-targeted therapies in patients with gastric cancer should be conducted. These trials could also explore the use of MISP as a biomarker for patient selection and treatment monitoring. Collaboration between academic institutions, healthcare providers, and pharmaceutical companies will be crucial to advance these efforts [5,6].

Conclusion

The overexpression of MISP in gastric cancer and intestinal metaplasia highlights its potential as a biomarker and therapeutic target. MISP plays a critical role in mitotic spindle positioning, and its dysregulation may contribute to gastric tumorigenesis. The evidence from gene expression studies and clinical samples supports the association between MISP overexpression and poor prognosis in gastric cancer. Moreover, MISP could serve as a diagnostic marker for early detection and risk assessment in patients with intestinal metaplasia. Future research and clinical trials will be essential to fully realize the potential of MISP in improving the diagnosis, prognosis, and treatment of gastric cancer.

Acknowledgement

None.

Conflict of Interest

None.

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