Colon neoplasia is one of the major malignancies in industrialized countries due to their Western-style food habits. It accounts for more than 50% of the population developing adenomatous polyps by the age of 70 years, but 10% of cancers in developed countries. The aim of this study was to evaluate the pathological role of the C-X-C chemokine receptor type 4/stromal-derived factor 1 axis (CXCR4-SDF-1 axis), and the inhibitory molecules PD-1 and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) in postoperative colon cancer patients undergoing treatment with chemotherapy (oxaliplatin and capecitabine) and estimate the correlation between these studied factors to deeply understand the basic mechanisms and potential diagnostic or therapeutic effects. The study involved 90 patients, including 50 colon cancer patients (male and female, aged 35-65) diagnosed by oncologists at Al-Ramadi Hospital, Ramadi, Iraq. All patients underwent surgical resection and received four cycles of chemotherapy with oxaliplatin (85 mg every 21 days) and capecitabine (6 grams daily for 21 days). Additionally, 40 age- and sex-matched individuals served as the control group. For each participant, CXCR4 and SDF-1 levels were measured using ELISA and the gene expression of CTLA-4 and PD-1 were measured using RT-PCR. The colon cancer patient group showed significantly lower levels of CXCR4 and SDF-1 compared to control groups (0.163±0.012 vs 0.376±0.025 pg/mL and 0.376±0.025 vs 0.699±0.110 pg/mL, respectively, both had p=0.001). Moreover, the colon cancer patient group had significantly lower expression of PD-1 and CTLA4 compared to control group (0.102±0.029-fold vs 1.199±0.391-fold, p=0.02; and 0.302±0.140-fold vs 1.441±0.334-fold, p=0.008, respectively). In conclusion, the results suggest that CXCR4 and SDF-1 appear promising as diagnostic markers for distinguishing colon cancer patients from healthy conditions.

Colorectal cancer (CRC), is the third most prevalent cancer across the globe, and is often detected at advanced stage. Late diagnosis of CRC, leave the chemotherapy and radiotherapy as the main options for the possible treatment of the disease which are associated with severe side effects. In the present study, we seek to explore CRC gene expression data using a systems biology framework to identify potential biomarkers and therapeutic targets for earlier diagnosis and treatment of the disease.

The expression data was retrieved from the gene expression omnibus (GEO). Differential gene expression analysis was conducted using R/Bioconductor package. The PPI network was reconstructed by the STRING. Cystoscope and Gephi software packages were used for visualization and centrality analysis of the PPI network. Clustering analysis of the PPI network was carried out using k-mean algorithm. Gene-set enrichment based on Gene Ontology (GO) and KEGG pathway databases was carried out to identify the biological functions and pathways associated with gene groups. Prognostic value of the selected identified hub genes was examined by survival analysis, using GEPIA.

A total of 848 differentially expressed genes were identified. Centrality analysis of the PPI network resulted in identification of 99 hubs genes. Clustering analysis dissected the PPI network into seven interactive modules. While several DEGs and the central genes in each module have already reported to contribute to CRC progression, survival analysis confirmed high expression of central genes, CCNA2, CD44, and ACAN contribute to poor prognosis of CRC patients. In addition, high expression of TUBA8, AMPD3, TRPC1, ARHGAP6, JPH3, DYRK1A and ACTA1 was found to associate with decreased survival rate.

Our results identified several genes with high centrality in PPI network that contribute to progression of CRC. The fact that several of the identified genes have already been reported to be relevant to diagnosis and treatment of CRC, other highlighted genes with limited literature information may hold potential to be explored in the context of CRC biomarker and drug target discovery.

Approximately 20% of colorectal cancer (CRC) patients present with metastasis at diagnosis. Among Stage I-III CRC patients who undergo surgical resection, 18% typically suffer from distal metastasis within the first three years following initial treatment. The median survival duration after the diagnosis of metastatic CRC (mCRC) is only 9 mo. mCRC is traditionally considered to be an advanced stage malignancy or is thought to be caused by incomplete resection of tumor tissue, allowing cancer cells to spread from primary to distant organs; however, increasing evidence suggests that the mCRC process can begin early in tumor development. CRC patients present with high heterogeneity and diverse cancer phenotypes that are classified on the basis of molecular and morphological alterations. Different genomic and nongenomic events can induce subclone diversity, which leads to cancer and metastasis. Throughout the course of mCRC, metastatic cascades are associated with invasive cancer cell migration through the circulatory system, extravasation, distal seeding, dormancy, and reactivation, with each step requiring specific molecular functions. However, cancer cells presenting neoantigens can be recognized and eliminated by the immune system. In this review, we explain the biological factors that drive CRC metastasis, namely, genomic instability, epigenetic instability, the metastatic cascade, the cancer-immunity cycle, and external lifestyle factors. Despite remarkable progress in CRC research, the role of molecular classification in therapeutic intervention remains unclear. This review shows the driving factors of mCRC which may help in identifying potential candidate biomarkers that can improve the diagnosis and early detection of mCRC cases.

RNA modification has recently become a significant process of gene regulation, and the methyltransferase-like (METTL) family of proteins plays a critical role in RNA modification, methylating various types of RNAs, including mRNA, tRNA, microRNA, rRNA, and mitochondrial RNAs. METTL proteins consist of a unique seven-beta-strand domain, which binds to the methyl donor SAM to catalyze methyl transfer. The most typical family member METTL3/METTL14 forms a methyltransferase complex involved in N6-methyladenosine (m6A) modification of RNA, regulating tumor proliferation, metastasis and invasion, immunotherapy resistance, and metabolic reprogramming of tumor cells. METTL1, METTL4, METTL5, and METTL16 have also been recently identified to have some regulatory ability in tumorigenesis, and the rest of the METTL family members rely on their methyltransferase activity for methylation of different nucleotides, proteins, and small molecules, which regulate translation and affect processes such as cell differentiation and development. Herein, we summarize the literature on METTLs in the last three years to elucidate their roles in human cancers and provide a theoretical basis for their future use as potential therapeutic targets.

Leptin is an adipocyte-derived hormone with a critical role in energy balance. As demonstrated by previous investigations, leptin acts as a proliferative and angiogenic factor in cancer cells. However, results regarding its role in colorectal cancer are still inconclusive. We aimed to evaluate serum leptin and tissue expression of leptin receptor (Ob-R) in normal and malignant samples of colorectal.

Serum and tissue samples from pathology-confirmed colorectal cancer patients and normal controls referring to a university hospital of Mazandaran were obtained during 2019-21. ELISA and immunohistochemistry were applied to determine leptin and Ob-R expression respectively.

A total of 90 samples belonging to 46 normal and 44 CRC patients were enrolled. Normal and CRC groups included 32 (69.56%) and 21 (47.72%) female subjects respectively. The average leptin concentration in the normal group was 115.80 and, in the patient, group was 124.47 ng/mL (P=0.897). CRC cases showed an insignificantly higher Ob-R detection rate (P=0.086).

There was no significant difference in leptin and Ob-R expression between CRC patients and normal subjects. Thus, leptin and its receptor may not be useful as a biomarker of CRC.

Despite the abnormal expression of 18S rRNA m6A methyltransferase METTL5 being reported in some types of human malignancies, but its effect on hepatocellular carcinoma (HCC) remains to be unclear. This study aims to elucidate the influences of METTL5 on the carcinogenesis and progression of HCC. Expressions of METTL5 gene, transcript, protein, and promoter methylation in HCC were examined through multiple databases, c-BioPortal was used to confirm the genomic alterations of METTL5, the biological functions, target networks of kinases and microRNAs of METTL5, and its interactive differential genes were investigated through LinkedOmics. The possible correlation of METTL5 with the tumor-related infiltration of immune cells for HCC were explored comprehensively by using the online tools of TIMER and TISIDB. Expressions of METTL5 gene, mRNA, and protein were considerably overexpressed in HCC samples in comparison with healthy samples. The high methylation of the METTL5 promoter was observed in HCC tissues. Elevated METTL5 expression exhibited unfavorable survival outcomes in HCC patients. METTL5 expression were enriched in the signaling pathways of ribosome and oxidative phosphorylation, mismatch repair, and spliceosome through the involvement of several cancer-related kinases and miRNAs. The METTL5 expression has a positive correlation with the infiltration degree of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells in HCC. Marker genes of tumor immune-infiltrated cells have strong connection with METTL5. Furthermore, the upregulation of METTL5 was strongly correlated with the immune regulation of immunomodulators, chemokines, and chemokine receptors in the immune microenvironment. The oncogenesis and development of HCC are closely related to METTL5 expression, and the overexpression of METTL5 resulted in the poor survival outcome of HCC patients by regulating tumor immune microenvironment.

Methotrexate is the conventional disease-modifying anti-rheumatic drug (DMARD) which is considered the drug of choice in the treatment of rheumatoid arthritis, but its prolonged use without monitoring leads to a number of complications involving different body systems. The toxic effects of long-term methotrexate (MTX) therapy mainly involve the liver, skin, gastrointestinal tract (GIT) and bone marrow. In the bone marrow, it mainly causes suppression of normal functionality, leading to the formation of abnormal blast cells and dysplasia. In this case report, we present a male patient with symptoms of hoarseness, fatigue and abnormal bleeding all of which can be affiliated with methotrexate-induced hypoplastic myelodysplasia. As pancytopenia can be a lethal complication of MTX toxicity, it is important to monitor the therapy and dosage of methotrexate so that in case of any unforeseen development of a complication vital steps may be taken to diagnose and treat it in time. Regarding our patient, after thorough history taking and undergoing extensive hematological workup, the diagnosis of MTX-induced hypoplastic myelodysplasia was made. His symptoms improved on withholding the drug methotrexate from his active regimen and adding folinic acid and colony-stimulating factors.

Intercellular communication plays an important role in cancer initiation and progression through direct contact and indirect interactions, such as via secretory molecules. Cancer-associated fibroblasts (CAFs) are one of the principal components of such communication with cancer cells, modulating cancer metastasis and tumour mechanics and influencing angiogenesis, the immune system, and therapeutic resistance. Over the past few years, there has been a significant increase in research on extracellular vesicles (EVs) as regulatory agents in intercellular communication. EVs enable the transfer of functional molecules, including proteins, mRNAs and microRNAs (miRNAs), to recipient cells. Cancer cells utilize EVs to dictate the specific characteristics of CAFs within the tumour microenvironment, thereby promoting cancer progression. In response to such "education" by cancer cells, CAFs contribute to cancer progression via EVs. In this review, we summarize experimental data indicating the pivotal roles of EVs in intercellular communication between cancer cells and CAFs.