ABSTRACT
BACKGROUND: Perirectal epidermoid cysts are rare masses arising from the ectodermal germ cell layer of the hindgut and are predominantly found in middle-aged women. It is often difficult to make an accurate diagnosis of these cysts and it is equally challenging to distinguish it from other developmental cysts. CASE SUMMARY: We report the case of an 18-year-old female patient with a perirectal mass who presented to the hospital with constipation. The patient experienced sacrococcygeal falls and burns on the left buttocks during growth. Three-dimensional computed tomography scans indicated abnormal sacral vertebrae with the sacral canal partially enlarged and opened. Pelvic magnetic resonance imaging showed a 55 mm × 40 mm × 35 mm unilocular cystic mass in the perirectal space and a solitary sinus in the left ischiorectal fossa. The cyst was completely resected posteriorly using the sacrococcygeal approach. The pathology was verified to be an epidermoid cyst. The patient remained recurrence-free after 6 mo of follow-up. CONCLUSION: Successful treatment of perirectal epidermoid cysts depends on comprehensive evaluation. This is significant for the surgical approach and prognosis.
ABSTRACT
According to a recent report by GLOBOCAN, colorectal cancer is the third most common and second most deadly cancer in 2020. In our previous proteomic study, we found that the expression of GSTM2 in colon tissues was significantly lower than that in para-cancer tissues, and its lower expression was associated with reduced overall survival rate of patients, suggesting that this gene might play a role in the occurrence of colon cancer. As a member of the detoxifying enzyme family, GSTM2 is likely to play an important role in the initiation of tumors. Whereas, the functions of GSTM2 in colon cancer are barely known. In this study, using the RNA-Seq datasets of colon cancer patients from public database (ntumor = 457, nnormal = 41), we confirmed the reduced expression of GSTM2 and its prognostic value in colon cancer. Furthermore, we used our own Chinese cohort (ntumor = 100, nnormal = 72) verified the lower GSTM2 expression in colon cancer, and also its effects on patient prognosis. Subsequently, we uncovered two potential reasons for the lower expression of GSTM2 in colon cancer tissues, including the deep deletion of GSTM2 on genome, and the up-regulation of RAD21 or SP1. Moreover, we disclosed that GSTM2 might be involved in several immune-related pathways in colon cancer, such as chemokine signaling and leukocyte transendothelial migration. Finally, we revealed that the GSTM2 expression was closely related to the immune-related scores of colon cancer and the infiltration ratios of various immune cells, suggesting that GSTM2 might regulate the development of colon cancer by modulating immune microenvironment. In conclusion, we uncovered the prognostic value of GSTM2 based on the public data and our own data, revealed its potential regulatory role in tumor immune microenvironment, and disclosed the probable reasons for its lower expression in colon cancer. The findings of our study provide a potential prognostic biomarker and drug target for clinical diagnosis and treatment of colon cancer.
ABSTRACT
Ferroptosis is a type of programmed cell death potentially playing an important role in colorectal cancer (CRC) development. However, comprehensive investigations toward ferroptosis in human CRC are lacking. Here, we performed multiple investigations on cancer and para-cancer tissues. We demonstrated that the changes of structural variation and chromatin accessibility in CRC were more associated with the altered mRNA expression of ferroptosis-related genes (FRGs), and the expression of CDKN2A, GPX4, ALOXE3, and LINC00336 was related to the overall survival rates. Subsequently, we revealed that CYBB and YAP1 were potentially the hub genes, and that HSF1 and STAT2 were potentially FRGs' upstream transcription factors. Finally, we depicted the crosstalk between ferroptosis and necrosis, autophagy, and apoptosis. Based on multi-dimensional analyses, we characterized ferroptosis, probable core genes, and the upstream regulators in human CRC. The findings here may improve our understanding of ferroptosis in CRC and provide new opportunities for clinical diagnosis and treatment.
ABSTRACT
Background: The disturbed molecular alterations of nucleus may promote the development of colorectal cancer (CRC). A multi-platform-based analysis of nucleus of CRC patients helps us to better understand the underlying mechanism of CRC and screen out the potential drug targets for clinical treatment. However, such studies on nucleus in human CRC are still lacking. Methods: We collected the cancerous and para-cancerous tissues from eight CRC patients and performed a multiplex analysis of the molecular changes of the nucleus, including structural variations (SVs), DNA methylation, chromatin accessibility, proteome and phosphorproteome. Results: In our study, we revealed a significant molecular change of nucleus of CRC patients using our original proteomic and phosphorylomic datasets. Subsequently, we characterized the molecular alterations of nucleus of CRC patients at multiple dimensionalities, including DNA, mRNA, protein and epigenetic modification. Next, we found that the great molecular changes of nucleus might affect the biological processes named endocytosis and ubiquitin-mediated proteolysis. Besides, we identified DYNC1LI2 and TPR as the potentially hub proteins within the network of nuclear genes in CRC cells. Furthermore, we identified 1905 CRC-specific SVs, and proclaimed 17 CRC-specific SVs were probably associated with the disturbance of immune microenvironment of CRC patients. We also revealed that the SVs of CXCL5, CXCL10 and CXCL11 might be the core SVs among all the immune-relevant SVs. Finally, we identified seven genes as the upstream transcriptional factors potentially regulating the expression of nuclear genes, such as YY1 and JUN, using a multi-omics approach. Conclusion: Here, we characterized the molecular changes of nucleus of CRC patients, disclosed the potentially core nuclear genes within the network, and identified the probable upstream regulator of nucleus. The findings of this study are helpful to understand the pathogenic molecular changes of nucleus in CRC patients and provide a functional context for drug development in future.
ABSTRACT
Nowadays, among all urinary system cancers, the mortality of kidney cancer (KC) has risen to the first, and the incidence has been keeping on the third. Many recent studies have demonstrated that m6A modification regulated by the methyltransferases (writers) is closely related to the tumorigenesis of multiple cancers. In our previous study, we found that the methyltransferase METTL5 had a stronger association with the hazard ratio of KC more than most tumors, indicating its special function in carcinogenesis of KC. Until now, the expression, functions and mechanism of METTL5 in KC are still unclear. In this study, we analyzed the mRNA expression of METTL5 using the data sets from public databases, and revealed that the METTL5 expression was significantly up-regulated in tumor tissues of kidney renal clear cell carcinoma (KIRC) and kidney renal papillary cell carcinoma (KIRP) compared to normal tissues. Also, the METTL5 expression was correlated with the tumor stage and grade, indicating the potential involvement of METTL5 in tumor progression. Additionally, the higher expression of METTL5 predicted poorer prognosis of KIRC and KIRP patients. Subsequently, we revealed that the functions of METTL5 in KIRC might be related to immune modulation, because its co-expressed gene were enriched in immune-relevant pathways including Th17 cell differentiation, Th1 and Th2 cell differentiation, and phosphatidylinositol 3-kinase activity. Next, we disclosed that the METTL5 expression was correlated to the microenvironment score and immune score of KIRC and KIRP, and associated with the infiltration ratios of 25 types of immune cells. Besides, we demonstrated a wide difference of the METTL5's effect on the survival of patients with high and low immune infiltration, further suggesting METTL5 might affect tumor development via modulating the immune microenvironment. The findings of our study provide a novel potential prognostic biomarker and immune drug target for KC.
ABSTRACT
BACKGROUND: Stomach adenocarcinoma (STAD) is a common reason for tumor-related fatalities globally, as it results in distant metastasis. Methyltransferase-like 14 (METTL14), a notable RNA N6-adenosine methyltransferase (m6A), plays a significant role in the growth of tumor through controlling the RNA working. This study aims to highlight METTL14 in STAD's biological function and molecular mechanism. METHODS: Bioinformatics and immunohistochemical (IHC) assays have been utilized for the detection of METTL14 expression in the STAD. METTL14's biological function has been shown while making use of HGC-27 and AGS cells in vitro experiments. MeRIP-qPCR and luciferase reporter assays were employed for the exploration of METTL14's mechanism modifying the target of phosphatase and tensin homologue (PTEN). Subcutaneous xeno transplantation model and STAD liver metastasis orthotopic tumor model were used to study METTL14 in STAD in vivo. RESULTS: METTL14 expression was substantially downregulated in STAD reflecting contribution to major tumors, progressed TNM stage as well as poor overall survival (OS) in STAD. Moreover, METTL14's inhibition of STAD cells proliferation, migration and invasion has been verified in vitro assays. Furthermore, an identification of PTEN being METTL14-mediated m6A modification's substrate has been made. METTL14's overexpression highly enhanced PTEN mRNA m6A variation, stabilized PTEN mRNA and increased protein expression. Further, it has been found out that METTL14-mediated STAD cells inhibition of proliferation and invasion dependent on PTEN. At last, we demonstrated that METTL14 inhibit STAD growth and metastasis in vivo models. CONCLUSIONS: METTL14 inhibits tumor growth and metastasis of STAD via stabilization of PTEN mRNA expression. Therefore, METTL14 is a potential biomarker of prognosis and therapeutic targets for STAD.
ABSTRACT
BACKGROUND: Over expression of galectin-3 (gal-3) has been associated with tumor invasion and distant metastases, but few reports investigated the relation between gal-3 expression and prognosis in stage II colon cancer. OBJECTIVE: We studied the expressions of gal-3, E-cadherin, and vimentin in stage II colon cancer to identify predictive factors of clinical outcome. METHODS: Clinical and laboratory data from 117 consecutive patients of stage II colon cancer during 2008-2010 were collected and analyzed retrospectively. Expressions of gal-3, E-cadherin, and vimentin in tumor tissue were investigated by immunohistochemistry. Potential correlations between these markers and various clinicopathological parameters as well as clinical outcomes were studied. Human colon cancer cell line SW480 was used to test the epithelial-mesenchymal transition (EMT) inducing effects of gal-3 in vitro. RESULTS: High expression of tumoral gal-3 was associated with tumor size, poor differentiation and negatively related to low E-cadherin expression. Compare with adjacent normal colon tissue, most tumor tissues strongly expressed gal-3 and vimentin, but had lower E-cadherin expression. Univariate analysis showed that expressions of gal-3 and vimentin in tumor were predictors of tumor recurrence and overall survival. Multivariate analysis revealed that tumoral gal-3 expression was the only independent predictor of both tumor recurrence and overall survival after resection. Cell experiments and western blotting showed exogenous gal-3 could induce SW480 cells become more aggressive and express more hallmarks of EMT. CONCLUSIONS: Galectin-3 may be a useful marker for identification of poor prognosis in stage II colon cancer. Cell experiments and western blotting showed exogenous gal-3 could induce SW480 cells become more aggressive and express more hallmarks of EMT.
