Gene expression analysis of the concomitant existence of lymphovascular and perineural invasion in colorectal cancer

The invasion of cancer cells into the peritumoral, lymph node and perineural system could be detrimental on cancer patients. In colorectal cancer (CRC) patients, the presence of lymphovascular (LVI) and/or perineural (PNI) invasion could significantly influence on the survival rates, treatment options and recurrence tendencies. To date, no study has analyzed the molecular profile of the concomitant existence of LVI and PNI in CRC. Here, we reanalyzed The Cancer Genome Atlas (TCGA) CRC datasets and focused on cases where the information regarding LVI and PNI are available (n=176). We performed differential gene expression, methylation and microRNA analysis by comparing the groups having both or either LVI and PNI with the control group (LVI negative and PNI negative). Although there was no significant difference in the methylation and miRNA profiles, we identified a number of differentially expressed genes (DEGs). The comparison between the LVI+PNI+ and LVI-PNI- groups revealed key DEGs including SFTA2, PHACTR3, CRABP2, ODZ3, GRP, HAP1, CSDC2, TMEM59L and HDAC9. Meanwhile, in the LVI-PNI+ vs LVI-PNI- group, some of the DEGs found were PTPRR, EFNA2, FGF20, IGFL4, METRN and IGFBPL1. We believe that this study could be beneficial and add value to further understand the complex molecular profiles of CRC

miR-205 in situ expression and localization in head and neck tumors - a tissue array study

Background: microRNAs are small non-coding RNA that control gene expression by mRNA degradation or translational inhibition. These molecules are known to play essential roles in many biological and physiological processes. miR-205 may be differentially expressed in head and neck cancers; however, there are conflicting data and localization of expression has yet to be determined. Materials and Methods: miR-205 expression was investigated in 48 cases of inflammatory, benign and malignant tumor tissue array of the neck, oronasopharynx,larynx and salivary glands by Locked Nucleic Acid in situ hybridization (LNA-ISH) technology. Results: miR-205 expression was significantly differentially expressed across all of the inflammatory, benign and malignant tumor tissues of the neck. A significant increase in miR-205 staining intensity (p<0.05) was observed from inflammation to benign and malignant tumors in head and neck tissue array, suggesting that miR-205 could be a biomarker to differentiate between cancer and non-cancer tissues. Conclusions: LNA-ISH revealed that miR-205 exhibited significant differential cytoplasmic and nuclear staining among inflammation, benign and malignant tumors of head and neck. miR-205 was not only exclusively expressed in squamous epithelial malignancy. This study offers information and a basis for a comprehensive study of the role of miR-205 that may be useful as a biomarker and/or therapeutic target in head and neck tumors

miRNAs and lncRNAs as Predictive Biomarkers of Response to FOLFOX Therapy in Colorectal Cancer

Chemotherapy is one of the options for cancer treatment. FOLFOX is one of the widely used chemotherapeutic regimens used to treat primarily colorectal cancer and other cancers as well. However, the emergence of chemo-resistance clones during cancer treatment has become a critical challenge in the clinical setting. It is crucial to identify the potential biomarkers and therapeutics targets which could lead to an improvement in the success rate of the proposed therapies. Since non-coding RNAs have been known to be important players in the cellular system, the interest in their functional roles has intensified. Non-coding RNAs (ncRNAs) as regulators at the post-transcriptional level could be very promising to provide insights in overcoming chemo-resistance to FOLFOX. Hence, this mini review attempts to summarize the potential of ncRNAs correlating with chemo-sensitivity/resistance to FOLFOX

Differential microRNA expression and identification of putative miRNA targets and pathways in head and neck cancers.

MicroRNAs (miRNAs) are small noncoding RNAs that involved in various cancer-related cellular processes. Diverse studies on expression profiling of miRNAs have been performed and the data showed that some miRNAs are up-regulated or down-regulated in cancer. Until now, there are no data published on the miRNA expression in head and neck cancers from Malaysia. Hence, this study aimed to investigate potentially crucial miRNAs in head and neck cancer patients from Malaysian populations. A global miRNA profiling was performed on 12 samples of head and neck cancer tissue using microarray analysis followed by validation using real-time RT-PCR Microarray analysis identified 10 miRNAs that could distinguish malignant head and neck cancer lesions from normal tissues; 7 miRNAs (hsa-miR-181a-2*, hsa-miR-29b-1*, hsa-miR-181a, hsa-miR-181b, hsa-miR-744, hsa-miR-1271 and hsa-miR-221*) were up-regulated while 3 miRNAs (hsa-miR-141, hsa-miR-95 and hsa-miR-101) were down-regulated. These miRNAs may contribute in a simple profiling strategy to identify individuals at higher risk of developing head and neck cancers, thus helping in the elucidation of the molecular mechanisms involved in head and neck cancer pathogenesis

Deep Transcriptome Sequencing of Pediatric Acute Myeloid Leukemia Patients at Diagnosis, Remission and Relapse: Experience in 3 Malaysian Children in a Single Center Study

Among the many types of leukemia, acute myeloid leukemia (AML) affects 20% of diagnosed hematological malignancies in pediatric patients (Meshinchi and Arceci, 2007; de Rooij et al., 2015). Standard chemotherapy regimen remains as the first line treatment for pediatric AML, however nearly 40% of AML patients may suffer from relapse and eventually die from the disease (de Rooij et al., 2015). Similarly, it has been reported that 50% of the pediatric AML relapsed within 12–18 months of diagnosis and 45% of those relapsed were not expected to survive (Creutzig et al., 2014). Despite advances in cytogenetic analysis through fluorescence in situ hybridization and multiplex PCR, there is still a need for a better and comprehensive molecular profiling. For instance, microarray has long been used to study the gene expression profiles of AML patients. The different profile of gene expression has enabled clinicians to tailor better treatment for patients and predict whether patients have the tendency to relapse (Goswami et al., 2009). In a recent study, Handschuch et al. reported that three genes, ANXA3, S100A9, and WT1 can differentiate between different prognostic types of AML (Handschuh et al., 2018). The study outcome was in agreement with another study conducted by Shimada et al. (2012), where a high expression of WT1 gene showed prognostic impact in pediatric AML (Shimada et al., 2012). Another study by Jo et al. (2015) reported that high expression of EVI1 and MEL1 could predict the prognosis of pediatric AML (Jo et al., 2015). However, none of the biomarkers identified from these studies have been translated into clinical use. Therefore, the search continues for additional promising biomarkers, notably novel transcripts, novel fusion genes and non-coding RNAs which are not represented in the microarray platform. Transcriptome sequencing through next generation sequencing represents an effective approach to discover new genetic information on gene expression which may contribute to tumorigenesis. Notably, several novel and rare fusion transcripts have been identified from AML patients via RNA-sequencing (Padella et al., 2015). A recent study combining whole genome sequencing, whole exome sequencing and RNA sequencing in pediatric cancers has identified 240 pathogenic variants with increased sensitivity (Rusch et al., 2018). Previous studies in relapsed AML have shown that the cells acquired additional genetic mutations that were either different or evolved from subclones of diagnostic blasts cells (Padella et al., 2015; Rusch et al., 2018). Nevertheless, little is known about the genetic changes at the transcriptomic level at diagnostic, remission and relapse stages of the same patients, especially in the Malaysian population

Diversity and Antimicrobial Activities of Actinobacteria Isolated from Tropical Mangrove Sediments in Malaysia

The aim of this study was to isolate and identify Actinobacteria from Malaysia mangrove forest and screen them for production of antimicrobial secondary metabolites. Eighty-seven isolates were isolated from soil samples collected at 4 different sites. This is the first report to describe the isolation of Streptomyces, Mycobacterium, Leifsonia, Microbacterium, Sinomonas, Nocardia, Terrabacter, Streptacidiphilus, Micromonospora, Gordonia, and Nocardioides from mangrove in east coast of Malaysia. Of 87 isolates, at least 5 isolates are considered as putative novel taxa. Nine Streptomyces sp. isolates were producing potent antimicrobial secondary metabolites, indicating that Streptomyces isolates are providing high quality metabolites for drug discovery purposes. The discovery of a novel species, Streptomyces pluripotens sp. nov. MUSC 135T that produced potent secondary metabolites inhibiting the growth of MRSA, had provided promising metabolites for drug discovery research. The biosynthetic potential of 87 isolates was investigated by the detection of polyketide synthetase (PKS) and nonribosomal polyketide synthetase (NRPS) genes, the hallmarks of secondary metabolites production. Results showed that many isolates were positive for PKS-I (19.5%), PKS-II (42.5%), and NRPS (5.7%) genes, indicating that mangrove Actinobacteria have significant biosynthetic potential. Our results highlighted that mangrove environment represented a rich reservoir for isolation of Actinobacteria, which are potential sources for discovery of antimicrobial secondary metabolites

A panel of three microRNA signatures as a potential biomarker for CRC screening based on stages and functional prediction using bioinformatic analysis

Background: MicroRNA (miRNA) has been linked to colorectal cancer (CRC) tumorigenesis due to its post-transcriptional mechanism in targeting cancer-associated genes. Although miRNAs appear to be promising screening biomarkers, functional prediction analysis is required to shed light on their role in CRC tumorigenesis. Therefore, this study aims to identify the significantly deregulated miRNAs in CRC tumorigenesis. (2) Methods: Three upregulated miRNAs (hsa-miR-20a-5p, hsa-miR-21-5p, and hsa-miR210-3p) from 14 significant differentially expressed miRNAs (DEMs) were chosen from microarray profiling to be validated in plasma. Bioinformatics analyses showed that these miRNAs generally contributed to tumorigenesis, but only hsa-miR-20a-5p and hsa-miR-21-5p were specifically linked to CRC. Only two miRNAs showed a positive correlation when compared to their expression in plasma. However, further analysis showed that all three miRNAs in plasma were significantly difference between the early and advanced stages of CRC. ROC curve analysis was used to evaluate miRNAs’ diagnostic performance in the early and advanced stages. (3) Results: Collectively, hsa-miR-20a-5p showed the highest discriminative value (AUC= 0.82, sensitivity = 86%, and specificity= 88%) in discriminating early CRC, while both hsa-miR-21-5p and hsa-miR-210-3p give a perfect performance for advance CRC. In addition, the performance of all miRNAs’ combinations also gives a perfect performance for diagnosis in both early and advanced CRC, except the combination of hsa-miR-20a-5p and hsa-miR-210-3p. (4) Conclusions: A few potential miRNA panels as CRC biomarker is needed for better prediction of disease. The reflective circulating miRNAs can be contributed to by minimal invasive screening tools

Vibrio vulnificus: An Environmental and Clinical Burden

Vibrio vulnificus is a Gram negative, rod shaped bacterium that belongs to the family Vibrionaceae. It is a deadly, opportunistic human pathogen which is responsible for the majority of seafood-associated deaths worldwide. V. vulnificus infection can be fatal as it may cause severe wound infections potentially requiring amputation or lead to sepsis in susceptible individuals. Treatment is increasingly challenging as V. vulnificus has begun to develop resistance against certain antibiotics due to their indiscriminate use. This article aims to provide insight into the antibiotic resistance of V. vulnificus in different parts of the world as well as an overall review of its clinical manifestations, treatment, and prevention. Understanding the organism's antibiotic resistance profile is vital in order to select appropriate treatment and initiate appropriate prevention measures to treat and control V. vulnificus infections, which should eventually help lower the mortality rate associated with this pathogen worldwide

Microrna expression and assessment of potential role of miR-181a in head and neck cancer

MicroRNAs (miRNAs) represent a class of small non-coding RNAs that regulate gene expression by either inducing mRNA degradation or repressing mRNA translation. The involvements of miRNAs in various human cancer-related processes have been studied in recent years. The first objective of this study was to determine differentially expressed miRNAs in head and neck cancer. Global miRNA profiling was performed on 12 tissue samples from various head and neck cancers by using the microarray approach followed by real time RT-PCR validation. The microarray analyses identified 10 miRNAs that were able to distinguish malignant from normal tissues whereby seven miRNAs (hsa-miR-181a-2*, hsa-miR-29b-1*, hsa-miR-181a,hsa-miR-181b, hsa-miR-744, hsa-miR-1271 and hsa-miR-221*) showed upregulation while three miRNAs (hsa-miR-141, hsa-miR-95 and hsa-miR-101) showed down-regulation. Therefore, these miRNAs may aid in simple profiling strategies to identify individuals at higher risk of developing head and neck cancers, as well as elucidate the molecular mechanisms involved in head and neck cancers pathogenesis. The second objective of this study was to identify the putative targets of miRNAs differentially expressed in head and neck cancers and the pathways involved, which was achieved through in silico analysis aided by online databases, whereby several cancer-associated genes and pathways were found to be targeted by miR-181a. The role of miR-181a in head and neck carcinogenesis was subsequently determined through functional analyses as the third objective of this study. It was found out that miR-181a regulates the proliferation, migration, invasion and colony-forming ability of head and neck cancer cell. Fourth objective was achieved by using pathway analysis to profile changes in the activities of 10 signaling pathways related to cancer caused by miR-181a downregulation. Six of these pathways, namely the p53/DNA damage, TGFβ, MAPK/ERK, MAPK/JNK, Wnt and NFκB pathways, were found to be significantly influenced, suggesting miR-181a may act as an oncomiR, and therefore its inhibition may be a potential therapeutic target for head and neck cancer patients. The fifth and final objective of this study involved visualizing miR-181a expression and localization in head and neck tissues, for which in situ hybridization was utilized. miR-181a is preferentially expressed in the cytoplasm of cancer cells, and its expression is significantly increased in malignant compared to benign tumors of the head and neck. Collectively, these findings provide basis for study into the role of miR-181a as a biomarker and/or therapeutic target in head and neck tumors