The most common forms of primary brain tumors are low-grade astrocytoma (ACT) tumors and their progression to the glioblastoma multiforme (GBM), in a high-aggressiveness form. Understanding mechanisms of progression is necessary, and mitochondrial mechanisms are not yet as well elucidated and may be a factor in this disease. Therefore, in this study, we analyzed differential gene expression (DGE) between GBM and ACT, using the MitoXplorer 2.0 to screen nuclear genes involved in mitochondrial metabolism, totaling 1,193 genes. The analysis used ACT (n = 195) and GBM (n = 157) samples made available by The Cancer Genome Atlas (TCGA) database. As a complement, we checked the expression of differentially expressed genes (DEGs) in normal tissues using the GTEx Portal, as well as checking disease-free survival (DFS) using GEPIA2. DGE showed five potential DEGs, three of which were downregulated (ACSM2A, ACSM2B, and PRODH2) and two were upregulated (TERT and FBP2). In non-cancerous tissues, upregulated DEGs are normally expressed basally in brain tissue and TERT is normally expressed in tissues such as testis and small intestine, while FBP2 is expressed in the stomach, skeletal muscle, testis, pancreas, and adrenal glands. Alternatively, downregulated DEGs normally show basal or zero expression in brain tissues and are normally expressed in the liver and kidneys. DFS analysis showed that the high expression of the TERT is associated with poor survival, and is the only gene found to be significant among the five DEGs (p-value < 0.05). Briefly, our analyses showed five mitochondrial DEGs as potential markers of GBM progression in relation to ACT. Four of the five DEGs have not been reported as factors that can influence the GBM cascade until this work, while the TERT gene has already been indicated as a potential biomarker of brain cancer, having an essential function in the protection of the mitochondrial genome.

AIMS:
Medulloblastoma (MBs), the most prevalent malignant paediatric brain tumour, exhibits distinct subgroups—Wingless (WNT), Sonic Hedgehog (SHH), Group 3 (G3), and Group 4 (G4)— each characterized by unique molecular signatures and clinical outcomes. Despite being the most aggressive, Group 3 (G3) and Group 4 (G4) remain the least understood. Current treatments, involving surgical resection, radiation, and chemotherapy, are associated with significant morbidity and adverse effects. This study aims to explore the potential of clinically significant doses of simvastatin, known for its ability to penetrate the blood-brain barrier, as a targeted and less toxic therapy for aggressive MBs.

METHOD:
In-silico gene expression analysis assessed mevalonate pathway (MVP) enzyme expression in MBs, corroborated by immunocytochemistry and RT-PCR in SHH, G3, and G4 cells. The anti-cancer and anti-metastatic properties of low doses of simvastatin were investigated through both 2D and 3D cell culture methods.

RESULTS:
Our findings reveal that clinically significant doses of simvastatin effectively reduces the migration of MBs cells in both 2D and 3D in vitro cultures.

CONCLUSIONS:
This study establishes simvastatin as a promising therapeutic candidate for mitigating MBs cell invasion, offering a potential avenue for the development of novel and less invasive treatment strategies for MBs tumours.

Lung cancer remains a formidable global health challenge, necessitating the exploration of innovative diagnostic approaches for early detection. This review paper delves into the burgeoning field of exhaled breath analysis using electronic nose (e-nose) technology for the identification of volatile organic compounds (VOCs) as potential biomarkers for lung cancer diagnosis. An electronic nose inspired by the human olfactory system comprises an array of sensors that can detect and differentiate complex odor profiles. This paper elucidates the principles behind e-nose technology and its application in capturing the unique VOC signatures present in exhaled breath, which serve as indicators of underlying physiological conditions. A significant portion of this review is dedicated to elucidating the methodology and advancements in e-nose-based VOC analysis, providing insights into the potential of this non-invasive approach for disease diagnosis. The exploration extends beyond general applications to specifically spotlight the utilization of e-nose technology in the realm of early lung cancer detection. E-nose-based disease diagnosis, and more specifically, lung cancer detection, is discussed in detail, with an emphasis on the recent studies and advancements. The potential of VOC profiling as a reliable and early diagnostic tool for lung cancer is explored, addressing both the promises and challenges associated with this cutting-edge approach. This comprehensive review amalgamates the current state of knowledge in the field, offering a roadmap for future research opportunities and the realization of e-nose technology's promise in revolutionizing lung cancer diagnosis.

Introduction: Genome-wide association studies (GWASs) have contributed to the study of neuroblastoma (NB) genetics by identifying common risk variants that activate cancer-related processes associated with NB susceptibility.

Aim: This study aims to functionally characterize the 11p11.2 predisposition locus identified in our GWAS on 2101 cases and 4202 controls, evaluating how the regulatory variant and its target gene can influence NB development.

Methods: To identify functional variants, we annotated 72 candidate SNPs with functional data from public NB databases and validated the functional SNP’s regulatory activity vialuciferase assays in NB cells. The candidate SNP was predicted to map inside a GATA3 binding motif and differential GATA3 allele binding was evaluated using ChIP-qPCR. eQTL analysis and CRISPR/Cas9 genome editing allowed us to identify the target gene of the functional SNP. To evaluate its role in NB tumorigenesis, we correlated gene expression with clinical features using RNA-seq data from 498 tumors and performed MTT and invasion assays after gene silencing in NB cells. Targeted lipidomic assays were performed to study the involvement of the target gene in lipid metabolism.

Results: rs2863002T>C represents the candidate functional SNP of the risk locus. The rs2863002-C allele correlated with high expression levels of its target gene HSD17B12 and showed a lower binding affinity for the transcription factor GATA3 in NB cells, suggesting that it may alter the GATA3 binding motif. High HSD17B12 expression levels correlated with poor prognosis and survival in NB tumors, and gene silencing in NB cells reduced proliferation and invasiveness, supporting the oncogenic role of HSD17B12 in NB. Lipidomic results showed that HSD17B12 silencing in NB cells altered lipid metabolism, affecting lipid molecules related to energy production and cellular membrane chemical—physical properties.

Conclusions: This study highlights the importance of the post-GWAS functional characterization of risk loci to identify new susceptibility genes and new biological mechanisms underlying NB predisposition.

Gastric cancer (GC) is the second most common cause of death of any cancer-related cases in the world, and is also in the top 5 most common malignancy cancers in general. There are plenty of well-distributed treatments , offering better hygiene, more robust and complete nutrition, and the eradication of pathogens such as Helicobacter pylori. Currently, there is still the need for more treatments, especially those of lower cost, like those coming from already easily available products. Quercetin (QRC) is a natural phenolic compound present in a wide variety of products, e.g., in plants like Hibiscus sabdariffa, onions, grapes, broccoli, and citrus fruits. This product has been shown to have great potential therapeutic effects, and it has also been suggested that it could be useful in combating different types of cancer; however, information regarding the targets or mechanisms that QRC has on cancer cells is still unclear. Therefore, this study aims to identify the targets that QRC has, like anti-cancer treatment for GC using different bio-informatic tools and databases. From MalaCards and SwissTargetPrediction, both QRC and GC molecular targets were defined, and then they were matched with the Venny 2.1.0 platform. From this, 31 genes were gathered, and then they were analyzed using the ShinnyGo0.77 and DAVID-Bioinformatic Resources. Furthermore, StringDB was used to identify the protein—protein interactions, and Citoscape 3.6.0 12 hub genes were obtained. Those hub genes were then subject to Gene Expression Profiling Interactive Analysis and TISIDB. Finally, molecular docking studies were performed using the SwissDock database. The results suggest that, according to the gene ontology data, QRC has a relationship with the regulation of cell death, response to stress, cell motility, response to amyloid-beta, cellular response to reactive oxygen species, and apoptotic processes. Some genes like EGFR were correlated with an abundance of CD8 and Neutrophil infiltration, but didn’t show to improve the survival rate. Furthermore, molecular docking results show that QRC can bind to multiple molecules of interest. These results complement some of the currently available information alluding to the effectiveness of plants rich with QRC as part of the treatment used for different kinds of cancer, but it also suggests a plethora of new targets that this molecule has in GC, while at the same time giving a clearer idea of the mechanisms that are affected in GC by QRC. However, as with any other study that primarily uses bioinformatic tools, these final results are to be used for more direct and precise research, especially if experimental protocols are used.

Hepatocellular Carcinoma (HCC), a formidable global health challenge, continues to claim numerous lives due to its asymptomatic nature in the early stages and limited treatment options. In this ever-evolving landscape of cancer research, pseudogenes, once relegated to the genetic sidelines as 'non-functional,' have emerged as intriguing players. Contrary to their historical dismissal, pseudogenes are now recognized for their intricate roles in modulating gene expression and contributing to the complex molecular milieu of cancer. This comprehensive review delves into the uncharted territory of pseudogenes and their potential to revolutionize HCC detection and treatment. From deciphering the molecular connections between pseudogenes and HCC to exploring their utility as diagnostic biomarkers, prognostic indicators, and therapeutic targets, this article aims to solvethe enigma of pseudogenes in hepatocellular carcinoma.

Background: Cancer has become a significant public health issue and is one of the world's leading causes of death. This study reports on the types and distribution of cancer using data from the Hadhramout Oncology Center (HNOC) from 2015 to 2020.
This study aims to estimate the cancer incidence among patients registered at (HNOC) from 2015 to 2020.

Method: Retrospective descriptive study of patients diagnosed with cancer at (HNOC) in the period of 2015-2020 in Yemen.

Results: The results obtained from the Hadhramout National Oncology Center during the period 2015-2020 showed a total of 2591 cases. Of these, 1279 cases (49.4%) were males and 1312 (50.6%) were females, with a female-to-male ratio of 1.02. There has been an increase in the number of cases from 2015 to 2020 with a peak occurring in 2018. The mean ages of diagnosis were 52.29 and 50.45 years for males and females, respectively. For all cancer types, cancers of blood were the most common type, followed by breast cancer and colorectal cancer. Breast cancer (28.9%) and blood cancer (18.84%) were the most common types in females and males, respectively. Among all the cases registered at (HNOC), Hadramout had the highest reported cases with 1787 (68.9%), followed by Shabwa 518 (20%) and Almahra 105 (4.1%).

Conclusion: The findings of this study demonstrated that cancer incidence has increased over the past few years. Therefore, it is essential to establish a high-quality regional cancer registry to allow for the surveillance of cancer and facilitate the development of effective programs for cancer control and prevention in Yemen.

Background: Serum tumor markers have been shown to correlate with the prognosis of gastric cancer (GC); however, the effects of the dynamics of serum tumor markers (cancer antigen (CA)72-4, carcinoembryonic antigen (CEA), CA19-9, CA125, and alpha-fetoprotein (AFP)) on the prognosis of GC before and after neoadjuvant chemotherapy (NACT) remain unclear.

Methods: Data from 334 patients with GC who underwent NACT followed by radical gastrectomy between January 2016 and December 2021 were included in the present study. Tumor marker regression load (ΔTMRL) indicator, including ΔCA72-4, ΔCEA, ΔCA19-9, ΔCA125, and ΔAFP, is defined as [(postNACT marker – preNACT marker) / preNACT marker]. Based on the results of Cox regression analysis, the tumor marker regression load score (TMRLS) was composed of ΔCA72-4, ΔCEA, and ΔCA125. The predictive performance of the nomogram-TMRLS was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC), decision curve analysis (DCA), and C-index.

Results: The patients were divided into two groups, TMRLS-low and TMRLS-high, based on the optimal breakpoint of TMRLS determined in R using the maxstat package. Survival analysis revealed a higher 3-year overall survival (OS) in the TMRLS-low than in the TMRLS-high group (69.8% vs. 34.8%, respectively; P < 0.001). Those in the TMRLS-high group who received postoperative adjuvant chemotherapy (AC) showed a significantly higher 3-year OS rate than those who did not (52.3% vs. 8.3%, respectively; P = 0.020). Multivariate Coxregression analysis indicated that TMRLS was an independent prognostic factor for OS. A nomogram for predicting OS based on TMRLS, ypT stage, ypN stage, and AC showed a significantly higher C-index and AUC than the traditional ypTNM stage (C-index, 0.794 vs. 0.697, respectively; P < 0.001; AUC, 0.827 vs. 0.678, respectively; P < 0.001).

Conclusion: TMRLS appears to be a novel independent prognostic factor for patients with GC who underwent NACT and a radical gastrectomy. Furthermore, the TMRLS-high group, who received postoperative AC, achieved better survival outcomes. Of note, the predictive performance of the nomogram-TMRLS significantly outperformed that of the ypTNM stage.

Background: Oxidative stress in blood is associated with gastric cancer (GC) prognosis, but the predictive value of an integrated oxidative stress score comprising multiple indicators remains uncertain.

Methods: Between 2009 and 2017, clinicopathological data from GC patients were split 7:3 for developing and validation cohorts. Using COX proportional hazards regression, we analyzed oxidative stress indicators to construct a Gastric Cancer Integrated Oxidative Stress Score (GIOSS). GIOSS and other indicators were evaluated for overall survival (OS) prediction using the AUC and C-index. Kaplan–Meier analysis assessed 5-year OS in high/low GIOSS groups, stratified by pTNM stage. A Cox proportional hazards regression model identified preoperative factors influencing OS, leading to a preoperative nomogram (preope-Nomogram). The model accuracy was assessed via the ROC, calibration curve, and decision curve analysis (DCA), validated in the validation cohort. The Kaplan–Meier analysis and log-rank tests compared survival among risk groups.

Results: The study included 3498 patients. GIOSS in the training cohort outperformed any single indicator in predicting 5-year OS (AUC=0.605; C-index=0.590). Low GIOSS values were associated with better 5-year survival, applicable across different pTNM stages (p<0.05). The preope-Nomogram, incorporating GIOSS, age, cT, and cN, aligned with the pTNM stage. The ROC, calibration curve, and DCA all demonstrated the model's excellent performance, consistent across validation and training cohorts. High GIOSS patients in pTNM II (p=0.010) and III (p<0.001) showed higher 5-year OS with adjuvant chemotherapy.

Conclusions: High GIOSS independently predicts 5-year OS in GC patients after surgery. The preope-Nomogram distinguishes patient prognosis in different pTNM stages and successfully identifies high-risk patients who would benefit from adjuvant chemotherapy.

The presence of checkpoint markers in cancer cells aids in immune escape. The identification of checkpoint markers and early cancer markers is of utmost importance to gain clarity regarding the relationship between colitis and progressive inflammation leading to cancer. Herein, the gene expression levels of checkpoint makers, cancer-related pathways, and cancer genes in colon tissues of mouse models of chronic colitis (Winnie and Winnie-Prolapse mice) using next-generation sequencing are determined. Winnie mice are a result of a Muc2 missense mutation. The identification of such genes and their subsequent expression and role at the protein level would enable novel markers for the early diagnosis of cancer in IBD patients. The differentially expressed genes in the colonic transcriptome were analysed based on the Kyoto Encyclopedia of Genes and Genomes pathway. The expression of several oncogenes is associated with the severity of IBD, with Winnie-Prolapse mice expressing a large number of key genes associated with development of cancer. This research presents a number of new targets to evaluate for the development of biomarkers and therapeutics.