Molecular Features and Targeted Therapies in Extrahepatic Cholangiocarcinoma: Promises and Failures

Rizzo, Alessandro; Tavolari, Simona; Ricci, Angela Dalia; Frega, Giorgio; Palloni, Andrea; Relli, Valeria; Salati, Massimiliano; Fenocchio, Elisabetta; Massa, Annamaria; Brandi, Giovanni

doi:10.3390/cancers12113256

Cited by 10 publications

(13 citation statements)

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“…Furthermore, genomic studies have paved the way towards the identification of a large number of targets, and the most promising therapeutic options for ICC originate from targeted therapies. 48 , 49 In the current landscape of medical oncology, the identification of specific biomarkers which could have prognostic value represents one of the critical challenges. 49 Owing to the accessibility of CAC grade, more studies could be taken to find out the value of tumor markers and biochemical indexes predictive of response to ICC patients getting systemic therapies.…”

Section: Discussionmentioning

confidence: 99%

“… 48 , 49 In the current landscape of medical oncology, the identification of specific biomarkers which could have prognostic value represents one of the critical challenges. 49 Owing to the accessibility of CAC grade, more studies could be taken to find out the value of tumor markers and biochemical indexes predictive of response to ICC patients getting systemic therapies.…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Prognostic Value of Combined CA19-9 with Aspartate Aminotransferase to Lymphocyte Ratio in Patients with Intrahepatic Cholangiocarcinoma After Hepatectomy

Qiu¹,

Liu²,

Huang³

et al. 2021

CMAR

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Purpose The prognosis of intrahepatic cholangiocarcinoma (ICC) patients after surgical resection remains poor. Effective prognostic biomarkers are expected to stratify ICC patients and optimize their treatment strategies. To investigate the prognostic value of carbohydrate antigen 19-9 (CA19-9), aspartate aminotransferase to lymphocyte ratio index (ALRI), and their combination (CAC) in predicting long-term outcomes in ICC patients after hepatectomy. Patients and Methods ICC patients underwent initial hepatectomy for curative purpose from January 2009 to September 2017 were reviewed retrospectively. Area under the receiver operating characteristics curve (AUC) was used to distinguish the identification effectiveness of three different measures. Kaplan–Meier curves and Cox proportional hazards regression were used to assess the value of preoperative CAC grade in predicting overall survival (OS) and disease-free survival (DFS). Results A total of 530 patients were included and randomly divided into two groups (derivation cohort and validation cohort). During a median follow-up of 18 months (1–115.4 months), 317 patients (59.8%) died and 381 patients (71.9%) developed tumor recurrence. Lower ALRI, decreased serum CA19-9 level and CAC grade were found to be associated with better OS and DFS (both P <0.001). Importantly, the AUC for CAC grade was significantly greater than ALRI and CA19-9. In addition, results from Cox proportional hazards regression from both cohorts suggest that tumor number, node invasion, and CAC grade as independent prognostic factors for both OS and DFS. Conclusion This study demonstrated that CAC grade is a valuable biomarker for the prognosis of ICC patients. Specifically, patients with elevated CAC grades were correlated to worse long-term outcome after the hepatectomy. Our data suggest that increased CAC grades can be used to stratify patients and help to decide their treatment strategies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Prognostic Value of Combined CA19-9 with Aspartate Aminotransferase to Lymphocyte Ratio in Patients with Intrahepatic Cholangiocarcinoma After Hepatectomy

Qiu¹,

Liu²,

Huang³

et al. 2021

CMAR

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“…In 2018, ~219,420 new cases and 165,087 cases of mortality due to GBC were reported globally (7). Although surgical treatment is currently the most effective method for treating GBC, the majority of patients with GBC are typically already at metastatic or late clinical stages at diagnosis on presentation, limiting the curative treatment options (8)(9)(10). Therefore, it remains in high demand to develop novel precise targeted treatment methods to inhibit the progression of GBC whilst also improving the prognosis of treatment strategies.…”

Section: Introductionmentioning

confidence: 99%

HHLA2 promotes tumor progression by long non‑coding RNA H19 in human gallbladder cancer

Zhang

et al. 2022

Int J Oncol

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Advanced gallbladder cancer (GBC) is one of the most malignant of all types of biliary tract cancers that is associated with poor prognosis and high mortality. Accumulating evidence suggest that the B7 family of proteins serve an essential role in various types of cancers, including GBC. However, the potential function and regulatory mechanism of human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2; also known as B7-H7 or B7H5) in GBC remain poorly understood. In the present study, immunohistochemistry was used to examine the expression pattern of HHLA2 in samples from 89 patients with GBC. The possible association between HHLA2 expression and the clinicopathological parameters, including prognosis, were then assessed. Using lentiviruses, overexpression of HHLA2 plasmid or short-hairpin RNA (shRNA) of HHLA2 were transfected into GBC-SD cells to overexpress or knock down HHLA2 expression, respectively. The effects of HHLA2 overexpression and knockdown on the epithelial-mesenchymal transition (EMT) process on GBC-SD cells were measured by the western blotting and immunofluorescence staining of collagen I, N-cadherin, E-cadherin, vimentin and α-SMA. By contrast, changes in cell proliferation were measured using EdU assay. Cell invasion and migration were assessed using Transwell and wound-healing assays, respectively. In addition, a xenograft mouse model was established to evaluate the tumorigenic ability of the GBC cell line in vivo after stable transfection with lentivirus for HHLA2 overexpression or shRNA for HHLA2 knockdown. The regulatory relationships among TGF-β1, long non-coding RNA (lncRNA) H19 (H19) and HHLA2 were then investigated. The mRNA expression of lncRNA H19 were assessed using reverse transcription-quantitative PCR, whereas the expression levels of HHLA2 were detected by western blotting and immunofluorescence staining. HHLA2 expression was found to gradually increase as the stages of the GBC samples become more advanced. In addition, the expression level of HHLA2 was calculated to be positively associated with the Nevin stage, American Joint Committee on Cancer stage, tumor invasion and regional lymph node metastasis but was negatively associated with the overall patient survival (OS). In vitro experiments demonstrated that overexpression of HHLA2 promoted GBC migration, invasion, proliferation and EMT, whereas in vivo experiments found a promoting role of HHLA2 overexpression on GBC tumor growth. After transfection with lentiviruses encoding the overexpression plasmid of lncRNA H19, GBC migration, invasion, proliferation and EMT were increased. By contrast, knocking down HHLA2 expression suppressed TGF-β1- or lncRNA H19 overexpression-induced GBC migration, invasion, proliferation and EMT. In addition, HHLA2 knockdown significantly reduced the sizes of the GBC tumors in vivo . These results suggest that HHLA2 overexpression can promote GBC progression. Conversely, ablation...

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“…CDC is a malignant tumor with a poor prognosis (8), and little progress has been made in treatment, especially in the adjuvant setting (9)(10)(11). In addition, most studies on primary or metastatic CDC are case reports (12)(13)(14)(15) or series with small sample sizes (16)(17)(18), and a panoramic view of the clinicopathological features of the disease has not been established.…”

Section: Introductionmentioning

confidence: 99%

Cystic Duct Carcinoma: A New Classification System and the Clinicopathological Features of 62 Patients

et al. 2021

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BackgroundCystic duct carcinoma (CDC) is a rare biliary malignancy with a low incidence and poor prognosis. However, the clinical landscape of the disease has not been clarified and no widely applicable classification system has been developed.MethodsSixty-two patients with CDC were included in this retrospective study, and a new classification system was established using imaging data. Blood indices, radiological characteristics, pathological features, surgical procedures, and overall survival data were collected. The efficacy of the new classification in predicting resectability was evaluated using receiver operating characteristic (ROC) curves, and K-means clustering and t-distributed stochastic neighbor embedding were applied to verify the conclusion.ResultsThe pT stage of patients with type II CDC was significantly worse than that of type I. Patients with type II CDC were more likely to experience distant metastasis and invasion of the nervous system, vascular system, and liver. The resectability of patients with type II CDC was significantly worse than that of patients with type I CDC. Patients with type II CDC had worse prognoses. ROC curve analysis and K-means clustering revealed that the new classification could better categorize patients with CDC than currently available systems.ConclusionPatients with type II CDC have significantly worse clinicopathological outcomes. The new classification system has better accuracy in grouping patients with CDC.

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Molecular Features and Targeted Therapies in Extrahepatic Cholangiocarcinoma: Promises and Failures

Cited by 10 publications

References 99 publications

Prognostic Value of Combined CA19-9 with Aspartate Aminotransferase to Lymphocyte Ratio in Patients with Intrahepatic Cholangiocarcinoma After Hepatectomy

Prognostic Value of Combined CA19-9 with Aspartate Aminotransferase to Lymphocyte Ratio in Patients with Intrahepatic Cholangiocarcinoma After Hepatectomy

HHLA2 promotes tumor progression by long non‑coding RNA H19 in human gallbladder cancer

Cystic Duct Carcinoma: A New Classification System and the Clinicopathological Features of 62 Patients

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