molecular diagnosis of gallbladder cancer

Gallbladder cancer (GBC) is the sixth leading cause of death among digestive tract cancers, mainly due to late-stage diagnoses. Advanced GBC treatment often involves ineffective Chemotherapy. Early surgical removal is the best chance for a cure, highlighting the need for effective biomarkers for risk assessment and early detection. This study reviews potential molecular markers in GBC for precise diagnostics, emphasizing the urgent need for early diagnosis. Methods: This review was performed within articles published at PubMed, Science Direct, Google Scholar, and Web of Science until September ۲۰۲۴. The keywords were Gallbladder cancer, molecular biomarkers, cholecystitis, and RNA sequencing. By searching these databases, ۸۷ articles were found, and ۱۵ articles were selected under the inclusion criteria. Results: Inheritable variants linked to gallbladder cancer vulnerability, similar to polymorphisms in the risk- such receptors TLR۲ and TLR۴, the cytochrome P۴۵۰ ۱A۱( CYP۱A۱), and the ATP binding cassette ( ABC) transporter ABCG۸ genes, present implicit biomarkers for relating cases at elevated threat for GBC. This could enable prioritization of cholecystectomy, especially given the challenges of early opinion due to the lack of specific signs and symptoms. Likewise, Advancements in gallbladder cancer research have uncovered critical cellular and molecular factors affecting treatment, such as HER۲ variations and mutational burdens. Diagnosis depends on various molecular biomarkers, each with distinct limitations. Recent studies highlight potential candidates like long non-coding RNAs (lncRNAs) and genes linked to inflammation and tumor growth. Crucial molecular biomarkers for gallbladder cancer encompass long non-coding RNAs, genes associated with inflammation, mutations in TP۵۳, and tumor markers CA۱۹-۹ and CEA, along with p۵۳ and E-cadherin proteins, as well as circulating tumor DNA (ctDNA). These biomarkers exhibit different degrees of diagnostic precision and potential for early detection. While lncRNAs like HOTAIR, ANRIL, and H۱۹ demonstrate notable upregulation in GBC, markers such as VTN, CYP۴F۳, and AOX۱ have been associated with chronic cholecystitis and GBC. Alterations in the TP۵۳ gene are frequently observed in gallbladder carcinoma and correlate with a more aggressive tumor profile, resistance to Chemotherapy, and reduced overall survival rates. Nevertheless, widely utilized tumor markers like CA۱۹-۹ and CEA possess limited specificity for GBC, often resulting in false positives in benign cases. The expression levels of p۵۳ and E-cadherin proteins can fluctuate considerably, complicating their diagnostic effectiveness. Emerging as a valuable resource for detecting minimal residual disease, ctDNA can offer tailored insights but remains under assessment for clinical use. Conclusion: Despite identifying promising biomarkers for gallbladder cancer, validation is needed to improve treatment and prognosis. The advent of next-generation sequencing has increased our understanding of the molecular pathways involved in cancer and has led to the increased utility of microRNA-based gene regulation. Also, Chemotherapy remains the standard treatment, showing promising results by integrating cytotoxic agents with the complete drug. A combined approach, including miRNA-based interventions, may improve therapeutic issues and is a promising therapeutic strategy. However, this issue still needs further investigation and studies, underscoring the importance of ongoing research in this field.

کلیدواژه ها:

Gallbladder cancer ، molecular biomarkers ، cholecystitis ، RNA sequencing