Identification of Potential Protein Targets in Extracellular Vesicles Isolated from Chemotherapy-Treated Ovarian Cancer Cells.

Despite the ongoing clinical trials and the introduction of novel treatments over the past few decades, ovarian cancer remains one of the most fatal malignancies in women worldwide. Platinum- and paclitaxel-based chemotherapy is effective in treating the majority of patients with ovarian cancer. However, more than 70% of patients experience recurrence and eventually develop chemoresistance. To improve clinical outcomes in patients with ovarian cancer, novel technologies must be developed for identifying molecular alterations following drug-based treatment of ovarian cancer. Recently, extracellular vesicles (EVs) have gained prominence as the mediators of tumor progression. In this study, we used mass spectrometry to identify the changes in EV protein signatures due to different chemotherapeutic agents used for treating ovarian cancer. By examining these alterations, we identified the specific protein induction patterns of cisplatin alone, paclitaxel alone, and a combination of cisplatin and paclitaxel. Specifically, we found that drug sensitivity was correlated with the expression levels of ANXA5, CD81, and RAB5C in patients receiving cisplatin with paclitaxel. Our findings suggest that chemotherapy-induced changes in EV protein signatures are crucial for the progression of ovarian cancer.

Uncovering the role of FXYD3 as a potential oncogene and early biomarker in pancreatic cancer.

Pancreatic cancer is an aggressive cancer with silent symptoms and high mortality with less than 11% of the 5-year survival rate. Until now, the significance of genes as clinical biomarkers in the early stages of pancreatic cancer has not been fully understood. Hence, this study aims to reveal the significant genes in the early stages of pancreatic cancer using bioinformatic analysis and in vitro experiments, and to serve as clinical biomarkers for early detection. We used Cancer RNA-Seq Nexus database and identified one tumor suppressor gene (NAGK), and five oncogenes (FXYD3, ACTR1A, B3GNT3, SIGIRR, and EXOC1) that are significant in the early stages of pancreatic cancer. The expression of NAGK, FXYD3, ACTR1A, B3GNT3, SIGIRR, and EXOC1 were determined from the GEPIA, UALCAN, and HPA database. It has been shown that pancreatic cancer tumor dissemination is an event that can occur in early lesions, rather than being solely restricted in the developed primary tumor. Thus, the six hub genes that were differentially expressed between stage I and stage II of primary pancreatic cancer tumors were compared to metastasis-related genes (1938 genes) in the human cancer metastasis database (HCMDB), yielding two overlapped genes (B3GNT3 and FXYD3). To establish the expression correlation between these two specific genes with metastatic characteristics of the early stage of pancreatic cancer and migratory ability in pancreatic cancer cell lines, the expression patterns of B3GNT3 and FXYD3 were examined in four different migratory abilities of pancreatic cancer cell lines, including HPAC, BxPC-3, AsPC-1, and PANC-1, as well as the normal pancreatic duct epithelial cell line HPDE6-C7. The results displayed that the expression of the FXYD3 gene was dramatically increased with the migratory ability enhanced of four pancreatic cancer cell lines. Thus, in the follow-up study, we will demonstrate the functional role of FXYD3 in pancreatic cancer tumorigenesis. This study revealed that the FXYD3 may act as a significant oncogene in the early stage of pancreatic cancer.

Association of diabetes mellitus with early-onset colorectal cancer: A systematic review and meta-analysis of 19 studies including 10 million individuals and 30,000 events.

BACKGROUND AND AIMS: Early-onset colorectal cancer (EoCRC) constitutes 2%-10% of all colorectal cancers and is becoming more common globally. Diabetes mellitus (DM) has increased substantially in younger adults; however, its involvement in EoCRC remains unclear. We conducted a systematic review and meta-analysis of observational studies to (1) explore the prevalence of DM in individuals with EoCRC and (2) investigate the association between DM and EoCRC. METHODS: A systematic literature search was conducted to identify studies published before May 2022 that evaluated the association between DM and EoCRC risk in four databases, including Medline (PubMed), Embase, Web of Science, and the Cochrane Central Register of Controlled Trials. Results from the studies were summarized in meta-analyses using random effects models. RESULTS: Nineteen eligible studies were included. A total of 33,359 EoCRC cases and 14,259,289 controls in 12 studies were included in the meta-analysis. The pooled odds ratio [OR] of 1.43 (95% confidence interval [CI]: 1.08-1.8) indicated significant positive association between DM and increased risk of EoCRC. Subgroup analysis demonstrated that diabetes severity was significantly associated with unmanaged DM (OR = 1.28, 95% CI: 1.02-1.6), but not with managed DM (OR = 1.04, 95% CI: 0.84-1.28). CONCLUSION: Our results suggest that DM is a risk factor for EoCRC, and the higher prevalence of DM among younger adults may contribute to the increasing incidence of EoCRC. Interventions to reduce this bidirectional risk should be further investigated for the development of effective prevention and treatment strategies. PROSPERO registration: CRD42022306347.

Expression Profile and Prognostic Value of Wnt Signaling Pathway Molecules in Colorectal Cancer.

Colorectal cancer (CRC) is a heterogeneous disease with changes in the genetic and epigenetic levels of various genes. The molecular assessment of CRC is gaining increasing attention, and furthermore, there is an increase in biomarker use for disease prognostication. Therefore, the identification of different gene biomarkers through messenger RNA (mRNA) abundance levels may be useful for capturing the complex effects of CRC. In this study, we demonstrate that the high mRNA levels of 10 upregulated genes (DPEP1, KRT80, FABP6, NKD2, FOXQ1, CEMIP, ETV4, TESC, FUT1, and GAS2) are observed in CRC cell lines and public CRC datasets. Moreover, we find that a high mRNA expression of DPEP1, NKD2, CEMIP, ETV4, TESC, or FUT1 is significantly correlated with a worse prognosis in CRC patients. Further investigation reveals that CTNNB1 is the key factor in the interaction of the canonical Wnt signaling pathway with 10 upregulated CRC-associated genes. In particular, we identify NKD2, FOXQ1, and CEMIP as three CTNNB1-regulated genes. Moreover, individual inhibition of the expression of three CTNNB1-regulated genes can cause the growth inhibition of CRC cells. This study reveals efficient biomarkers for the prognosis of CRC and provides a new molecular interaction network for CRC.

Novel Insights into the Prognosis and Immunological Value of the SLC35A (Solute Carrier 35A) Family Genes in Human Breast Cancer.

According to statistics 2020, female breast cancer (BRCA) became the most commonly diagnosed malignancy worldwide. Prognosis of BRCA patients is still poor, especially in population with advanced or metastatic. Particular functions of each members of the solute carrier 35A (SLC35A) gene family in human BRCA are still unknown regardless of awareness that they play critical roles in tumorigenesis and progression. Using integrated bioinformatics analyses to identify therapeutic targets for specific cancers based on transcriptomics, proteomics, and high-throughput sequencing, we obtained new information and a better understanding of potential underlying molecular mechanisms. Leveraging BRCA dataset that belongs to The Cancer Genome Atlas (TCGA), which were employed to clarify SLC35A gene expression levels. Then we used a bioinformatics approach to investigate biological processes connected to SLC35A family genes in BRCA development. Beside that, the Kaplan-Meier estimator was leveraged to explore predictive values of SLC35A family genes in BCRA patients. Among individuals of this family gene, expression levels of SLC35A2 were substantially related to poor prognostic values, result from a hazard ratio of 1.3 (with 95 percent confidence interval (95% CI: 1.18-1.44), the p for trend (ptrend) is 3.1 × 10-7). Furthermore, a functional enrichment analysis showed that SLC35A2 was correlated with hypoxia-inducible factor 1A (HIF1A), heat shock protein (HSP), E2 transcription factor (E2F), DNA damage, and cell cycle-related signaling. Infiltration levels observed in specific types of immune cell, especially the cluster of differentiation found on macrophages and neutrophils, were positively linked with SLC35A2 expression in multiple BRCA subclasses (luminal A, luminal B, basal, and human epidermal growth factor receptor 2). Collectively, SLC35A2 expression was associated with a lower recurrence-free survival rate, suggesting that it could be used as a biomarker in treating BRCA.