Current and New Biomarkers for Early Detection, Prognostic Stratification, and Management of Gallbladder Cancer Patients

Abstract

Gallbladder cancer (GBC) is an aggressive disease that shows evident geographic variation and is characterized by a poor prognosis, mainly due to the late diagnosis and ineffective treatment. Genetic variants associated with GBC susceptibility, including polymorphisms within the toll-like receptors TLR2 and TLR4, the cytochrome P450 1A1 (CYP1A1), and the ATP-binding cassette (ABC) transporter ABCG8 genes, represent promising biomarkers for the stratification of patients at higher risk of GBC; thus, showing potential to prioritize cholecystectomy, particularly considering that early diagnosis is difficult due to the absence of specific signs and symptoms. Similarly, our better understanding of the gallbladder carcinogenic processes has led to identify several cellular and molecular events that may influence patient management, including HER2 aberrations, high tumor mutational burden, microsatellite instability, among others. Despite these reports on interesting and promising markers for risk assessment, diagnosis, and prognosis; there is an unmet need for reliable and validated biomarkers that can improve the management of GBC patients and support clinical decision-making. This review article examines the most potentially significant biomarkers of susceptibility, diagnosis, prognosis, and therapy selection for GBC patients, highlighting the need to find and validate existing and new molecular biomarkers to improve patient outcomes.

Meta-analysis of the diagnostic performance of serum carbohydrate antigen 19-9 for the detection of gallbladder cancer

“…Recognition of GBC in the early stage enables more effective treatment and improves prognosis, yet early diagnosis remains a challenging task due to the lack of specific symptoms and reliable markers. 2,3 As a cancer-associated antigen, CA19-9 is the most intensively studied tumor marker primarily applied for the management of pancreato-biliary tumors. However, the current use of CA19-9 for GBC is limited.…”

“…2 The only potentially curative treatment for GBC remains surgical resection with clear margins; however, the lack of non-invasive approaches able to accurately detect the silent neoplasm at early stages might, in part, result in a low curative resection rate. 3,4 Moreover, it remains unclear whether current evidence is rigorous enough to support the role of adjuvant systematic treatment. 4,5 An early diagnosis is therefore of great importance to develop optimal management options for patients with GBC and improve the outcomes.…”

“…A combination of clinical features, imaging techniques, and assessment of non-specific tumor markers is commonly employed for the detection of malignant tumors. 3 Analysis of tumor markers is considered to be convenient, rapid, and economic compared to imaging examination. Despite various tumor markers having been evaluated, controversies abound regarding the validation of these existing markers for the diagnosis of gallbladder malignancy.…”

Clinical Features and Prognostic Factors of Elderly Patients with Gallbladder Cancer: A Population-Based Study

“…Approximately 70% of malignancies and 85% of cancer-related deaths are expected to occur in the elderly population by 2030 [2]. As the fth most common gastrointestinal tract malignancy, gallbladder cancer (GBC) is a highly malignant tumor with a poor prognosis [3][4][5]. It is estimated that in 2020, there will be 2115,949 new cases of GBC and 84,695 new deaths from GBC worldwide [6].…”

“…Hence, elderly patients may represent a special subgroup that needs more clinical attention. Currently, radical surgery with lymph node dissection and chemotherapy are highly recommended for GBC, but the role of radiotherapy remains controversial [3,5,12,13]. However, the utility of these methods for the treatment of GBC in elderly patients is still unknown.…”