High Expression of Pd-1 in Circulating Cells of Patients With Advanced Colorectal Cancer Receiving Adjuvant Therapy
Muhammed A. BakhrebahMohammad NasrullahWesam H. AbdulaalMohammed HassanHalima SiddiquiHuda A. Al DoghaitherUlfat M. OmarNawal HelmiMohannad FallatahAyat B. Al‐GhafariMohammad Imran KhanHani Choudhry
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Abstract:
Among all cancer types, colorectal cancer is the third most common in men and the second most common in women globally. Generally, the risk of colorectal cancer increases with age, and colorectal cancer is modulated by various genetic alterations. Alterations in the immune response serve a significant role in the development of colorectal cancer. In primary cancer types, immune cells express a variety of inhibitory molecules that dampen the immune response against tumor cells. Additionally, few reports have demonstrated that classical chemotherapy promotes the immunosuppressive microenvironment in both tissues and immune cells. This study assessed the expression levels of genes using RT-qPCR associated with the immune system, including interferon-γ, programmed death-1, β2-microglobulin, human leukocyte antigen-A, CD3e, CD28 and intracellular adhesion molecule 1, in patients with colorectal cancer, as these genes are known to serve important roles in immune regulation during cancer incidence. Gene expression analysis was performed with the whole blood cells of patients with colorectal cancer and healthy volunteers. Compared with the normal controls, programmed death-1was highly expressed in patients with advanced-stage colorectal cancer. Furthermore, the expression of programmed death-1 was higher in patients receiving adjuvant therapy, which suggests the therapy dampened the immune response against tumor cells. The results of the present study indicate that classical adjuvant therapies, which are currently used for patients with colorectal cancer, should be modulated, and a combination of classical therapy with anti-programmed death-1 antibody should be conducted for improved management of patients with colorectal cancer.Keywords:
Adjuvant Therapy
Causes of cancer
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Objective To observe the expression of Claudin-2 in colorectal cancer tissues and to explore its relationship with the development and progression of colorectal cancer.Methods Immunohistochemical staining(SP method) was used to detect the expression of Claudin-2 in colorectal cancer tissue,adjacent normal tissue of colorectal cancer and normal tissue and investigate the correlation between expression of Claudin-2 in colorectal cancer tissue and the genesis and development of colorectal cancer.Results The expression of Claudin-2 in colorectal cancer tissues was significantly higher than those in the adjacent tissues of colorectal cancer and normal colorectal tissue(P0.05);besides,the expression of Claudin-2 in the colorectal cancer tissue was correlated with degree of differentiation,Dukes stages of colorectal cancer(P0.05).Conclusion The expression of Claudin-2 in colorectal cancer increases significantly in both positive rate and intensity compared with that in normal tissue.The higher expression of Claudin-2 may play an important role in the genesis and development of colorectal cancer.
Claudin
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Background. Colorectal cancer is a digestive tract malignant tumor, ranking the second mortality and the third incidence cancer worldwide. The abnormal expression of NEAT1 is related to the occurrence and development of colorectal cancer. However, the specific mechanism of NEAT1 mediated-inflammatory pathway in the progression of colorectal cancer is still unclear. Methods. In this study, expression of NEAT1 in colorectal cancer patients was analyzed by bioinformatics. Clinical samples including peripheral blood and colorectal cancer tissues were collected for qRT-PCR, Western blot, and immunohistochemistry assay. The role of NEAT1 in the colorectal cancer progression was further confirmed by both in-vivo and in-vitro functional experiments. Results. By bioinformatics prediction, it is found that NEAT1 expression level is significantly higher in the peripheral blood of patients with colorectal cancer and is associated with poor prognosis. In-vitro functional studies indicated that NEAT1 knockdown suppressed the proliferation and migration of colorectal cancer cells by mediating inflammatory response. In-vivo tumorigenesis experiments showed that NEAT1 knockdown suppressed tumor growth. Conclusion. Abnormal high expression level of NEAT1 in colorectal cancer tissues and cells leads to poor prognosis. Mechanistically, NEAT1 triggers off the proliferation and migration of colorectal cancer cells through promoting the inflammatory reaction. Clinically, the expression level of NEAT1 in serum may be a marker for diagnosis and prognosis of colorectal cancer.
Tumor progression
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Colorectal cancer is one of the most commonly diagnosed malignancies among males and females worldwide. Although China is a country with a low incidence of colorectal cancer, with the improvement of China's economy and lifestyle changes, the incidence rate in China has generally increased in recent years, and the morbidity and mortality of colorectal cancer rank fifth among those of all malignant tumours. Furthermore, despite recent improvements in screening strategies and treatments for colorectal cancer, the prognosis of advanced colorectal cancer is still poor, mainly due to the recurrence or distant metastasis of this disease. Thus, colorectal cancer still seriously threatens the health and life of people and is a major public health problem worthy of further study. Recently, accumulating evidence has revealed that colorectal carcinogenesis might be a multistep process driven by progressive genetic abnormalities, including changes in lncRNA expression. Moreover, a large number of studies have discovered and studied the abnormal expression of lncRNAs in colorectal cancer, providing a promising target for the diagnosis and treatment of colorectal cancer, which will promote human understanding of the pathogenesis of colorectal cancer and improve diagnosis and treatment. Therefore, in the present review, we mainly summarize the present status of colorectal cancer, the characteristics, functions and clinical perspectives of lncRNAs, and the current therapeutic methods used for colorectal cancer, especially the application of lncRNAs in the treatment of colorectal cancer. It is hoped that this review will give readers a new understanding of the roles of lncRNAs in colorectal cancer.
Causes of cancer
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Cancer is a leading cause of death and colorectal cancer is among the most lethal cancers (1, 2). We mined public microarray datasets (3, 4) to determine in an unbiased fashion and at the level of the transcriptome genes most differentially expressed in the primary tumors of patients with colorectal cancer (CRC). We found significant differential expression of the gene encoding guanylate cyclase activator 2A, GUCA2A, when comparing colorectal tumors to the tissue of origin, the colon. GUCA2A mRNA was present at significantly higher quantities in tumors of the colon as compared to normal colorectal tissue. Analysis of human survival data revealed that expression of GUCA2A in rectal tumors was correlated with overall survival in patients with rectal cancer with high neoantigen load. GUCA2A expression changes may be important for the initiation or progression of human CRC.
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Abstract Colorectal cancer is a crucial health-threatening problem. In recent years, the treatment of colorectal cancer has continued improved and update. But the prognosis of advanced colorectal cancer is still disappointing. Galecitn-9 is a member of the galectin family which has been verified to have multiple biological regulatory functions. Our team has been studying the clinical application of the galectin family in gastric and colorectal cancer. However, we do not yet unveil the correlation between Galecitn-9 and colorectal cancer. This study aimed to elucidate the expression of Galecitn-9 in colorectal cancer and the effect of Galecitn-9 on colorectal cancer proliferation, migration and invasion.
Clinical Significance
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Abstract Background As a phosphorylated protein, NOLC1 is mainly located in the nucleus and is highly expressed in a variety of tumors, participating in the regulation of cell proliferation and aging. This study further investigated the role of NOLC1 in colorectal cancer tumors, aiming to provide sufficient scientific evidence for the clinical treatment of colorectal cancer. Methods We used TCGA, GEO, TNMplot, GEPIA, and other databases to explore the expression level of NOLC1 in colorectal cancer patients, as well as the correlation between the clinical characteristics of colorectal cancer patients and their expression, and conducted the prognostic analysis. Immunohistofluorescence (IHF) staining verified the analytical results. Subsequently, KEGG and GO enrichment analysis was used to identify the potential molecular mechanism of NOLC1 promoting the occurrence and development of colorectal cancer. The influence of NOLC1 expression on the immune microenvironment of colorectal cancer patients was further investigated using the TIMER database. GDSC database analysis was used to screen out possible anti-colorectal cancer drugs against NOLC1. Finally, we demonstrated the effect of NOLC1 on the activity and migration of colorectal cancer cells by Edu Cell proliferation assay and Wound Healing assay in vitro. Results Our results suggest that NOLC1 is overexpressed in colorectal cancer, and that overexpression of NOLC1 is associated with relevant clinical features. NOLC1, as an independent risk factor affecting the prognosis of colorectal cancer patients, can lead to a poor prognosis of colorectal cancer. In addition, NOLC1 may be associated with MCM10, HELLS, NOC3L, and other genes through participating in Wnt signaling pathways and jointly regulate the occurrence and development of colorectal cancer under the influence of the tumor microenvironment and many other influencing factors. Related to NOLC1: Selumetinib, Imatinib, and targeted drugs such as Lapatinib have potential value in the clinical application of colorectal cancer. NOLC1 enhances the proliferation and migration of colorectal cancer cells. Conclusions High expression of NOLC1 as an independent prognostic factor for survival in patients with colorectal cancer. NOLC1 enhances the proliferation and migration of colorectal cancer cells. Further studies and clinical trials are needed to confirm the role of NOLC1 in the development and progression of colorectal cancer.
Hematology
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The long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a decreased risk for colorectal cancer. A major molecular target for cancer chemoprevention by these agents is the cyclooxygenase- 2 (COX-2) isoenzyme, although other molecular pathways can not be excluded. Data from both human and animal studies suggest that COX-2 is an early event of colorectal carcinogenesis. The NSAIDs, in the particular the newly developed COX-2 selective inhibitors, suppress colorectal tumor development in rodents and significantly reduce the number of colorectal polyps in patients suffering from familial adenomatous polyposis coli. In this paper current opinions regarding the role of COX inhibitors in colorectal cancer prevention are reviewed. Some perspectives derived from experimental and clinical studies, that might improve future approaches in the prevention of this malignancy, are also considered.
Cancer Prevention
COX-2 inhibitor
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Objective:To study the expression of mitosis checkpoint gene hsMAD2 in colorectal cancer. Methods:The expression of hsMAD2 gene mRNA in colorectal cancer and normal colorectal tissue of 18 cases was quantitatively detected by RT-PCR. Results:The ratio of hsMAD2 mRNA/ GAPDH mRNA in colorectal cancer and normal colorectal tissue were 0.1235±0.0752 and 0.0312±0.0598,respectively. The results suggested that the expression of hsMAD2 mRNA in colorectal cancer were significant higher than in normal colorectal tissue(P0.05). Conclusion:Compared with normal colorectal tissue,the expression of hsMAD2 mRNA in colorectal cancer was markedly increased. This probably indicated that to up-regulate the expression of hsMAD2 mRNA in colorectal cancer may be a very effective to abnormal proliferation of colorectal cancer cells. And hsMAD2 gene as a related gene to colorectal cancer can play an important role in colorectal cancer pathogenesis.
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