Expression of fibroblast activation protein and the clinicopathological relevance in distal cholangiocarcinoma

Byrling, Johannes; Sasor, Agata; Nilsson, Johan; Hilmersson, Katarzyna Said; Andersson, Roland; Andersson, Bodil

doi:10.1080/00365521.2019.1708449

Cited by 9 publications

(6 citation statements)

References 49 publications

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“…Immunohistochemistry showed high and very specific FAP expression in tumor stroma whereas GLUT1 was expressed mainly on cholangiocarcinoma tumor cells. A high expression level of FAP in tumor stroma was reported previously ( 23 , 27 ). Cholangiocarcinoma typically presents with a pronounced stromal compartment, which consists mainly of cancer-associated fibroblasts ( 28 , 29 ).…”

Section: Discussionsupporting

confidence: 75%

Superior Tumor Detection for⁶⁸Ga-FAPI-46 Versus¹⁸F-FDG PET/CT and Conventional CT in Patients with Cholangiocarcinoma

Pabst

Trajkovic‐Arsic²,

Cheung³

et al. 2023

J Nucl Med

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Section: Discussionsupporting

confidence: 75%

Superior Tumor Detection for⁶⁸Ga-FAPI-46 Versus¹⁸F-FDG PET/CT and Conventional CT in Patients with Cholangiocarcinoma

Pabst

Trajkovic‐Arsic²,

Cheung³

et al. 2023

J Nucl Med

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“…Table 1 shows the articles published between 2007 and 2023. Among the studies conducted to determine the association between FAP-α and metastasis, 13 studies were conducted in China ( 4 , 17 , 20 , 26 , 27 , 29 , 31 – 36 , 38 ), three studies in Japan ( 22 – 24 ), three studies in South Korea ( 21 , 25 , 30 ), two studies in Spain ( 16 , 19 ), and seven studies in seven countries such as Sweden ( 15 ), Switzerland ( 18 ), France ( 14 ), Egypt ( 13 ), USA ( 37 ), Germany ( 39 ), and Belgium ( 28 ). The majority of the included studies were designed as cohorts, and the most common methods used for FAP-α detection were immunohistochemistry and Western blotting.…”

Section: Resultsmentioning

confidence: 99%

Association of future cancer metastases with fibroblast activation protein-α: a systematic review and meta-analysis

Janani,

Poorkhani,

Amiriani

et al. 2024

Front. Oncol.

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IntroductionFibroblast activation protein-α (FAP-α) is a vital surface marker of cancer-associated fibroblasts, and its high expression is associated with a higher tumor grade and metastasis. A systematic review and a meta-analysis were performed to associate future metastasis with FAP-α expression in cancer.MethodsIn our meta-analysis, relevant studies published before 20 February 2024 were systematically searched through online databases that included PubMed, Scopus, and Web of Science. The association between FAP-α expression and metastasis, including distant metastasis, lymph node metastasis, blood vessel invasion, vascular invasion, and neural invasion, was evaluated. A pooled odds ratio (OR) with 95% confidence intervals (CI) was reported as the measure of association.ResultsA total of 28meta-analysis. The random-effects model for five parameters showed that a high FAP-α expression was associated with blood vessel invasion (OR: 3.04, 95% CI: 1.54–5.99, I2 = 63%, P = 0.001), lymphovascular invasion (OR: 3.56, 95% CI: 2.14–5.93, I2 = 0.00%, P < 0.001), lymph node metastasis (OR: 2.73, 95% CI: 1.96–3.81, I2 = 65%, P < 0.001), and distant metastasis (OR: 2.59; 95% CI: 1.16–5.79, I2 = 81%, P < 0.001). However, our analysis showed no statistically significant association between high FAP-α expression and neural invasion (OR: 1.57, 95% CI: 0.84–2.93, I2 = 38%, P = 0.161).ConclusionsThis meta-analysis indicated that cancer cells with a high FAP-α expression have a higher risk of metastasis than those with a low FAP-α expression. These findings support the potential importance of FAP-α as a biomarker for cancer metastasis prediction.

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“…All samples underwent histopathological reevaluation by an experienced gastrointestinal pathologist (A.S) blinded to the original assessment. The cohort has been previously described [23,24]. Staging was based on the American Joint Committee on Cancer (AJCC) 7th edition [5].…”

Section: Study Populationmentioning

confidence: 99%

Mass spectrometry-based analysis of formalin-fixed, paraffin-embedded distal cholangiocarcinoma identifies stromal thrombospondin-2 as a potential prognostic marker

Byrling

Kristl

et al. 2020

J Transl Med

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Background: Distal cholangiocarcinoma is an aggressive malignancy with a dismal prognosis. Diagnostic and prognostic biomarkers for distal cholangiocarcinoma are lacking. The aim of the present study was to identify differentially expressed proteins between distal cholangiocarcinoma and normal bile duct samples. Methods: A workflow utilizing discovery mass spectrometry and verification by parallel reaction monitoring was used to analyze surgically resected formalin-fixed, paraffin-embedded samples from distal cholangiocarcinoma patients and normal bile duct samples. Bioinformatic analysis was used for functional annotation and pathway analysis. Immunohistochemistry was performed to validate the expression of thrombospondin-2 and investigate its association with survival. Results: In the discovery study, a total of 3057 proteins were identified. Eighty-seven proteins were found to be differentially expressed (q < 0.05 and fold change ≥ 2 or ≤ 0.5); 31 proteins were upregulated and 56 were downregulated in the distal cholangiocarcinoma samples compared to controls. Bioinformatic analysis revealed an abundance of differentially expressed proteins associated with the tumor reactive stroma. Parallel reaction monitoring verified 28 proteins as upregulated and 18 as downregulated in distal cholangiocarcinoma samples compared to controls. Immunohistochemical validation revealed thrombospondin-2 to be upregulated in distal cholangiocarcinoma epithelial and stromal compartments. In paired lymph node metastases samples, thrombospondin-2 expression was significantly lower; however, stromal thrombospondin-2 expression was still frequent (72%). Stromal thrombospondin-2 was an independent predictor of poor disease-free survival (HR 3.95, 95% CI 1.09-14.3; P = 0.037). Conclusion: Several proteins without prior association with distal cholangiocarcinoma biology were identified and verified as differentially expressed between distal cholangiocarcinoma and normal bile duct samples. These proteins can be further evaluated to elucidate their biomarker potential and role in distal cholangiocarcinoma carcinogenesis. Stromal thrombospondin-2 is a potential prognostic marker in distal cholangiocarcinoma.

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Expression of fibroblast activation protein and the clinicopathological relevance in distal cholangiocarcinoma

Cited by 9 publications

References 49 publications

Superior Tumor Detection for⁶⁸Ga-FAPI-46 Versus¹⁸F-FDG PET/CT and Conventional CT in Patients with Cholangiocarcinoma

Superior Tumor Detection for⁶⁸Ga-FAPI-46 Versus¹⁸F-FDG PET/CT and Conventional CT in Patients with Cholangiocarcinoma

Association of future cancer metastases with fibroblast activation protein-α: a systematic review and meta-analysis

Mass spectrometry-based analysis of formalin-fixed, paraffin-embedded distal cholangiocarcinoma identifies stromal thrombospondin-2 as a potential prognostic marker

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Expression of fibroblast activation protein and the clinicopathological relevance in distal cholangiocarcinoma

Cited by 9 publications

References 49 publications

Superior Tumor Detection for68Ga-FAPI-46 Versus18F-FDG PET/CT and Conventional CT in Patients with Cholangiocarcinoma

Superior Tumor Detection for68Ga-FAPI-46 Versus18F-FDG PET/CT and Conventional CT in Patients with Cholangiocarcinoma

Association of future cancer metastases with fibroblast activation protein-α: a systematic review and meta-analysis

Mass spectrometry-based analysis of formalin-fixed, paraffin-embedded distal cholangiocarcinoma identifies stromal thrombospondin-2 as a potential prognostic marker

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Superior Tumor Detection for⁶⁸Ga-FAPI-46 Versus¹⁸F-FDG PET/CT and Conventional CT in Patients with Cholangiocarcinoma

Superior Tumor Detection for⁶⁸Ga-FAPI-46 Versus¹⁸F-FDG PET/CT and Conventional CT in Patients with Cholangiocarcinoma