Tumor-Related Molecular Regulatory Mechanisms of Long Non-Coding RNA RMST: Recent Evidence

Background: Long non-coding RNA rhabdomyosarcoma 2-associated transcript (LncRNA RMST) will affect every aspect of tumor progression, such as proliferation, translocation and apoptosis. As a result, RMST can be used as an attractive biomarker for early diagnosis and clinical therapies of different disease states. This article aims to review pathophysiological functions, molecular mechanisms as well as promising biotherapies of RMST in multiple tumors. Methods: Through the systematic induction and summary of 46 papers published in PubMed concerning this study, the molecular mechanisms of RMST in all kinds of tumors have been reviewed. Results: LncRNA RMST is a tumor-related regulatory mediator, aberrantly expressed in diverse tumors, regarding medullary thyroid cancer, hepatocellular carcinoma, endometrial carcinoma, colon cancer, pancreatic cancer, glioma, Wilm’s tumor and breast cancer. Furthermore, as a mechanism-based player, RMST probably guides the translation and post-translation modification, containing DNA methylation and SUMOylation. It is capable of regulating distinct tumor cells and stem cells of biological behaviors via various molecular pathways. Conclusion: LncRNA RMST, potentially as an original therapeutic target, is valuable in the occurrence, development and apoptosis of different tumors.

P2Y12 Purinergic Receptor and Brain Tumors: Implications on Glioma Microenvironment

Gliomas are the most common malignant brain tumors in adults, characterized by a high proliferation and invasion. The tumor microenvironment is rich in growth-promoting signals and immunomodulatory pathways, which increase the tumor’s aggressiveness. In response to hypoxia and glioma therapy, the amounts of adenosine triphosphate (ATP) and adenosine diphosphate (ADP) strongly increase in the extracellular space, and the purinergic signaling is triggered by nucleotides’ interaction in P2 receptors. Several cell types are present in the tumor microenvironment and can facilitate tumor growth. In fact, tumor cells can activate platelets by the ADP-P2Y12 engagement, which plays an essential role in the cancer context, protecting tumors from the immune attack and providing molecules that contribute to the growth and maintenance of a rich environment to sustain the protumor cycle. Besides platelets, the P2Y12 receptor is expressed by some tumors, such as renal carcinoma, colon carcinoma, and gliomas, being related to tumor progression. In this context, this review aims to depict the glioma microenvironment, focusing on the relationship between platelets and tumor malignancy.

Comprehensive Pan-Cancer Analysis on CBX3 as a Prognostic and Immunological Biomarker

Background: Increased evidence supports the relationship between chromobox protein homolog 3 (CBX3) and tumorigenesis of some cancers. However, the role of CBX3 in pan-cancers remains poorly defined. In the research, we aimed to investigate the prognostic value and the immunological functions of CBX3. Results: We explored the potential oncogenic roles of CBX3 in mRNA and protein levels based on the diverse databases, including the expression, the correlation with prognosis, tumor microenvironment (TME), DNA methylation, protein phosphorylation and enrichment analysis across all TCGA tumors. The results show that CBX3 is overexpressed in multiple cancers, and significant correlations exist between high expression and adverse prognosis in most tumor patients. We observed an enhanced phosphorylation level in uterine corpus endometrial carcinoma, colon cancer and lung adenocarcinoma. A distinct relationship was also found between CBX3 expression and TME, including immune infiltration of tumor-infiltrating lymphocytes (TILs) and cancer-associated fibroblasts (CAFs), immune score or matrix score, immune checkpoints. The correlative transcription factors and miRNAs of CBX3-binding hub genes were analyzed to investigate the molecular mechanism. Moreover, alcoholism and alteration of DNA cellular biology may be involved in the functional mechanisms of CBX3. Conclusion: The first pan-cancer study offers a relatively comprehensive cognition on the oncogenic roles of CBX3 as a prognostic and immunological marker in various malignant tumors.

CLINICAL PROFILE AND COLONOSCOPIC FINDINGS IN ADULT PATIENTS PRESENTED WITH CHRONIC DIARRHEA

Background: Chronic diarrhea is a common and challenging problem in all age groups particularly in the elderly. It accounts for signicant morbidity and mortality in adults. It can be caused by a number of both neoplastic and non neoplastic lesions. For accurate diagnosis of various colorectal lesions, colonoscopy is the gold standard, simple, convenient and cost effective procedure. The present study aims to scrutinize the clinical prole and colonoscopic ndings in patients with chronic diarrhea in a tertiary care centre in South India Method: st This is a hospital based prospective observational study conducted from 1 September 2018 to 30th September 2019 at Department of Gastroenterology, Government Kilpauk Medical College Chennai ,128 patients were included in the present study. Study was cleared by institutional ethics committee of the hospital. Results: We evaluated 128 patients (mean age 47.03,),66% of the patients were males, and majority of the patients were in the age group 50-59 years. The most common clinical presentation other than diarrhea was bleeding per rectum 42% followed by mass per abdomen (23%), abdominal pain (21%) and 14% had spurious diarrhea. Colonoscopy was normal in 13%, colorectal growth accounted for 32%, Mucosal ulceration in 23%, Ileocecal lesions in 17%, polyps in 15%. The most common diagnosis was carcinoma colon (34%), followed by IBD (UC-17%, Crohns-9%) Tuberculosis in 13%, Polyposis in 8%, SIBO and Chronic Pancreatitis in 5%each, Radiation proctitis and IBS in 3% each. Conclusion:Chronic diarrhea causes signicant mortality as age advances, the leading cause for which was found to be Carcinoma colon in this study. For accurate diagnosis of various colorectal lesions, colonoscopy is the gold standard, simple, convenient and cost-effective procedure.

SMALF: miRNA-disease associations prediction based on stacked autoencoder and XGBoost

Background Identifying miRNA and disease associations helps us understand disease mechanisms of action from the molecular level. However, it is usually blind, time-consuming, and small-scale based on biological experiments. Hence, developing computational methods to predict unknown miRNA and disease associations is becoming increasingly important. Results In this work, we develop a computational framework called SMALF to predict unknown miRNA-disease associations. SMALF first utilizes a stacked autoencoder to learn miRNA latent feature and disease latent feature from the original miRNA-disease association matrix. Then, SMALF obtains the feature vector of representing miRNA-disease by integrating miRNA functional similarity, miRNA latent feature, disease semantic similarity, and disease latent feature. Finally, XGBoost is utilized to predict unknown miRNA-disease associations. We implement cross-validation experiments. Compared with other state-of-the-art methods, SAMLF achieved the best AUC value. We also construct three case studies, including hepatocellular carcinoma, colon cancer, and breast cancer. The results show that 10, 10, and 9 out of the top ten predicted miRNAs are verified in MNDR v3.0 or miRCancer, respectively. Conclusion The comprehensive experimental results demonstrate that SMALF is effective in identifying unknown miRNA-disease associations.

Histopathological spectrum of lower Gastro-intestinal colonoscopic biopsy lesion with special reference to Her-2/neu expression in carcinoma colon

Cancer associated with colon is one of the principal risk factors from decease in women and men. Although importance growing aspect of human epidermis receptor2 (Her2) as a therapeutic target is rising its role as a biomarker in the form of predicting indicator within colorectal Cancer (CRC)is still a mystery. Present research is undertaken for evaluating the Her2/neu description in Cancer of the colon. This research comprises 256patientswith spectrum of histopathological treatment ranging from colitis to colorectal carcinoma at our department between 2015- 2017. Her2/neu Immunohistochemistry was done in the colorectal carcinoma and scores based on Ruschoff et al. Her-2 testing in gastric cancer. Out of a total number of 256 cases enrolled in our study group, the majority belonged to the age group of 40-60 years, with M: F ratio being 1.4:1. The commonest site of the lesion occurred in the rectum (43.75%) followed by ascending colon and caecum (12.08%). Non neoplastic lesions constituted about two third of all cases, the commonest being inflammatory bowel disease(21.48%). In benign neoplastic lesions of tubular adenoma was the commonest type, and in malignant commonest type was colorectal adenocarcinoma NOS(64.44%) followed by mucinous adenocarcinoma (22.22%). Because of more prominent membranous staining observed in high grade colorectal cancers, Her2neu expression is found to be an important predictive marker of carcinoma colon, especially the adenocarcinoma, NOS. Like Breast carcinoma, target oriented therapy can be instituted especially in Her 2/neu positive high grade and metastatic tumors.

BRAF Mutated Metastatic Colorectal Carcinoma (mCRC): A case report

Colorectal cancer (CRC) is the third and second most frequent cancer in men and women respectively. Although histologically similar, CRCs are diverse with respect to the underlying molecular mechanism which could be explored for planning treatment strategies. Chromosomal instability, microsatellite instability, and errors in the DNA repair mechanism are the most frequent molecular aberrations involved in various sub groups of CRCs. BRAF (v-Raf murine sarcoma viral oncogene homolog B) mutation is seen in 5-15 % of CRC, with a higher mutation rate in right sided colon cancer. Patients with BRAF V 600E mutation tends to have a poor prognosis with a median survival rate of less than 12 months. In terms of treatment these patients do not benefit from therapeutics targeting the EGFR so it is important for clinicians to be aware. Treatment options beyond standard chemotherapy are crucial to achieve better outcomes and the role of anti-EGFR therapy alone remains controversial. Current trials assessing combinations of molecular targeted agents have shown some promise. We report a case of a 32 year old female who presented with features of intestinal obstruction and pallor of skin and mucous membranes. Her blood test showed low Hb and a high serum CEA value and CT Abdomen revealed a large hepatic flexure growth with multiple liver metastasis. Colonoscopic biopsy showed moderately differentiated adenocarcinoma and molecular assay confirmed wild type K RAS and mutated BRAF. To the best of our knowledge there are no reported cases of BRAF mutated metastatic carcinoma colon from Nepal.