Pancreatic cancer (PanCa) is one of the most lethal cancers (survival ~ 12%). As the conventional therapeutic interventions are mostly futile, a deep understanding of the disease pathophysiology is an urgent need. Ion channels, located on cell membrane, contribute significantly to cancer hallmarks, through dysregulation of various ion translocation; however, the fundamental mechanisms remain uncertain.

To identify these oncochannels in Indian cohort of PanCa, we utilized 450 K data, published in our previous study, and identified potential pathways involved. Their expressions were evaluated using TCGA data and an independent Indian paired patient cohort (n = 20). The top genes were further validated using GEO and ScRNA seq dataset. Potential target ability of KCNJ5 was identified through molecular dynamic based drug designing.

A set of 7 differentially methylated and differentially expressed genes of ion-channel proteins namely KCNJ5, CACNB2, KCNA3, KCNA6, RASA3, GABBR2 and CLIC5 were identified in Indian PanCa cohort only. KCNJ5 was significantly upregulated and associated with worse survival in Indian cohort, whereas downregulated in TCGA and other Caucasians patient populations. Two TFs controlling the KCNJ5 expression are POU2F1 and POU3F1. Few predicted small molecules targeting Kcnj5 are, Amiloride, Vernakalant hydrochloride, Dalfampridine, Glyburide and Levcromakalim. It also showed notable interactions with a steroidal anticancer agent, protodioscin.

An onco-channel gene, KCNJ5 significantly upregulated, and showing adverse survival in highly expressed KCNJ5 group in Indian cohort of PanCa, can be targeted with Amiloride, Vernakalant hydrochloride, Dalfampridine, Glyburide Levcromakalim and protodioscin. This understanding can lead to novel target identification for PanCa therapy development.

Pancreatic cancer (PanCa) is a catastrophic disease, being third lethal in both the genders around the globe. The possible reasons are extreme disease invasiveness, highly fibrotic and desmoplastic stroma, dearth of confirmatory diagnostic approaches and resistance to chemotherapeutics. This inimitable tumor microenvironment (TME) or desmoplasia with excessive extracellular matrix accumulation, create an extremely hypovascular, hypoxic and nutrient-deficient zone inside the tumor. To survive, grow and proliferate in such tough TME, pancreatic tumor and stromal cells transform their metabolism. Transformed glucose, glutamine, fat, nucleotide metabolism and inter-metabolite communication between tumor and TME in synergism, impart therapy resistance, and immunosuppression in PanCa. Thus, a finer knowledge of altered metabolism would uncover its metabolic susceptibilities. These unique metabolic targets may help to device novel diagnostic/prognostic markers and therapeutic strategies for better management of PanCa. In this review, we sum up reshaped metabolic pathways in PanCa to formulate detection and remedial strategies of this devastating disease.

Hepatocellular carcinoma (HCC) is a leading liver cancer that significantly impacts global life expectancy and remains challenging to treat due to often late diagnoses. Despite advances in treatment, the prognosis is still poor, especially in advanced stages. Studies have pointed out that investigations into the molecular mechanisms underlying HCC, including mitochondrial dysfunction and epigenetic regulators, are potentially important targets for diagnosis and therapy. Mitoepigenetics, or the epigenetic modifications of mitochondrial DNA, have drawn wide attention for their role in HCC progression. Besides, molecular biomarkers such as mitochondrial DNA alterations and non-coding RNAs showed early diagnosis and prognosis potential. Additionally, natural compounds like alkaloids, resveratrol, curcumin, and flavonoids show promise in HCC show promise in modulating mitochondrial and epigenetic pathways involved in cancer-related processes. This review discusses how mitochondrial dysfunction and epigenetic modifications, especially mitoepigenetics, influence HCC and delves into the potential of natural products as new adjuvant treatments against HCC.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive tumor with a poor prognosis that poses challenges for diagnosis using traditional tissue-based techniques. DNA methylation alterations have emerged as potential and promising biomarkers for PDAC. In this study, we aimed to assess the diagnostic potential of a novel DNA methylation assay based on epigenetic-specific peptide nucleic acid (Epi-sPNA) in both tissue and plasma samples for detecting PDAC.

The study involved 46 patients with PDAC who underwent surgical resection. Epi-TOP pancreatic assay was used to detect PDAC-specific epigenetic biomarkers. The Epi-sPNA allowed accurate and rapid methylation analysis without bisulfite sample processing. Genomic DNA extracted from paired normal pancreatic and PDAC tissues was used to assess the diagnostic efficacy of epigenetic biomarkers for PDAC. Subsequent validation was conducted on cell-free DNA (cfDNA) extracted from plasma samples, with 10 individuals represented in each group: PDAC, benign pancreatic cystic neoplasm, and healthy control.

The combination of seven epigenetic biomarkers (HOXA9, TWIST, WT1, RPRM, BMP3, NPTX2, and BNC1) achieved 93.5% sensitivity and 96.7% specificity in discerning normal pancreatic from PDAC tissues. Plasma cfDNA, analyzed using these markers and KRAS mutations, exhibited a substantial 90.0% sensitivity, 95.0% specificity, and an overall 93.3% accuracy for discriminating PDAC. Notably, cancer antigen 19-9 and carcinoembryonic antigen both had an accuracy of 90.0%.

Our study suggests that analyzing seven differentially methylated genes with KRAS mutations in cfDNA using the novel Epi-TOP pancreatic assay is a potential blood-based biomarker for the diagnosis of PDAC.

As the Editor-in-Chief of World Journal of Gastroenterology, every week prior to a new issue's online publication, I perform a careful review of all encompassed articles, including the title, clinical and/or research importance, originality, novelty, and ratings by the peer reviewers. Based on this review, I select the papers of choice and suggest pertinent changes (e.g., in the title) to the Company Editors responsible for publication. This process, while time-consuming, is very important for assuring the quality of publications and highlighting important articles that Readers may revisit.

Liquid biopsies have emerged as groundbreaking tools for minimally invasive monitoring of cancer, encompassing the analysis of Cell-Free DNA (cfDNA), circulating tumor DNA (ctDNA) and exosomes. This paradigm shift offers an emerging approach for understanding tumor dynamics, treatment responses, and disease progression. Leveraging advancements in molecular biology and technology, liquid biopsies enable clinicians to gain intricate insights from peripheral blood, thereby transforming the landscape of cancer care. This review describes the clinical impact, technological innovations, and recent evidence surrounding the integration of ctDNA and exosome analysis in cancer monitoring. Through early detection, real-time treatment response assessment, and the tracking of minimal residual disease, liquid biopsies have redefined the standards of precision oncology. Key advancements in ctDNA analysis, such as high-throughput sequencing and digital PCR, empower the detection of actionable mutations with high sensitivity. Concurrently, the characterization of exosomal cargo, facilitated by next-generation sequencing and mass spectrometry, unveils the molecular nuances of tumors. Recent studies underscore the utility of these approaches, demonstrating their efficacy in predicting relapse, guiding therapeutic decisions, and ultimately improving patient outcomes. As the field continues to evolve, liquid biopsies hold promise not only as diagnostic tools but also as agents of personalized medicine, enabling precise navigation of the intricate landscape of cancer with minimally invasiveness.

Pancreatic cancer (PanCa) presents a catastrophic disease with poor overall survival at advanced stages, with immediate requirement of new and effective treatment options. Besides genetic mutations, epigenetic dysregulation of signaling pathway-associated enriched genes are considered as novel therapeutic target. Mechanisms beneath the deoxyribonucleic acid methylation and its utility in developing of epi-drugs in PanCa are under trails. Combinations of epigenetic medicines with conventional cytotoxic treatments or targeted therapy are promising options to improving the dismal response and survival rate of PanCa patients. Recent studies have identified potentially valid pathways that support the prediction that future PanCa clinical trials will include vigorous testing of epigenomic therapies. Epigenetics thus promises to generate a significant amount of new knowledge of biological and medical importance. Our review could identify various components of epigenetic mechanisms known to be involved in the initiation and development of pancreatic ductal adenocarcinoma and related precancerous lesions, and novel pharmacological strategies that target these components could potentially lead to breakthroughs. We aim to highlight the possibilities that exist and the potential therapeutic interventions.

Pancreatic cancer is one of the most lethal human malignancies, in part because it is often diagnosed at late stages when surgery and systemic therapies are either unfeasible or ineffective. Therefore, diagnosing pancreatic cancer in earlier stages is important for effective treatment. However, because the signs and symptoms may be nonspecific and not apparent until the disease is at a late stage, the timely diagnoses of pancreatic cancer can be difficult to achieve. Recent studies have shown that selective screening and increased usage of biomarkers could improve the early diagnosis of pancreatic cancer. In this review, we discuss recent advancements in the early detection of pancreatic ductal carcinoma and precancerous lesions. These include innovations in imaging modalities, the diagnostic utility of various biomarkers, biopsy techniques, and population-based surveillance approaches. Additionally, we discuss how machine learning methods are being applied to develop integrated methods of identifying individuals at high risk of developing pancreatic disease. In the future, the overall survival of pancreatic cancer patients could be improved by the development and adoption of these new methods and techniques.