Expression of Prostate-Specific Membrane Antigen in Tumor-Associated Vasculature Predicts Poor Prognosis in Hepatocellular Carcinoma

Jiao, Dian; Li, Yu; Fa, Yang; Han, Donghui; Wu, Jieheng; Shi, Shengjia; Tian, Feng; Z, Guo; Xi, Wenjin; Li, Guodong; Zhao, Aizhi; Yang, An‐Gang; Qin, Weijun; Wang, He; Wen, Weihong

doi:10.14309/ctg.0000000000000041

Cited by 48 publications

(77 citation statements)

References 33 publications

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“…Tumor parenchyma staining was positive in a majority of NSCLC samples (54 of 80), which is consistent with previous reports of anxA1 expression in lung tumors [37][38][39][40]. Although induction of anxA1 expression in lung tumor vasculature was not as prevalent and widespread as that seen in other tumor vascular targets, notably B7-H3 [8] and PSMA [65,66], these data validate anxA1 as a potential tumor vascular drug target in a proportion of human lung tumors.…”

Section: Plos Onesupporting

confidence: 89%

Upregulation of annexin A1 protein expression in the intratumoral vasculature of human non–small-cell lung carcinoma and rodent tumor models

et al. 2020

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Annexin A1 (anxA1) is an immunomodulatory protein that has been proposed as a tumor vascular target for antitumor biologic agents, yet to date the vascular expression of anxA1 in specific tumor indications has not been systematically assessed. Attempts to evaluate vascular anxA1 expression by immunohistochemistry are complicated by a lack of available antibodies that are both specific for anxA1 and bind the N-terminal-truncated form of anxA1 that has previously been identified in tumor vasculature. To study the vascular expression pattern of anxA1 in non-small-cell lung carcinoma (NSCLC), we isolated an antibody capable of binding N-terminal-truncated anxA1 27-346 and employed it in immunohistochemical studies of human lung specimens. Lung tumor specimens evaluated with this antibody revealed vascular (endothelial) anxA1 expression in five of eight tumor samples studied, but no vascular anxA1 expression was observed in normal lung tissue. Tumor microarray analysis further demonstrated positive vascular staining for anxA1 in 30 of 80 NSCLC samples, and positive staining of neoplastic cells was observed in 54 of 80 samples. No correlation was observed between vascular and parenchymal anxA1 expression. Two rodent tumor models, B16-F10 and Py230, were determined to have upregulated anxA1 expression in the intratumoral vasculature. These data validate anxA1 as a potential vascular anti-tumor target in a subset of human lung tumors and identify rodent models which demonstrate anxA1 expression in tumor vasculature.

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Section: Plos Onesupporting

confidence: 89%

Upregulation of annexin A1 protein expression in the intratumoral vasculature of human non–small-cell lung carcinoma and rodent tumor models

et al. 2020

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“…Importantly, patients with disease recurrence in our study had longer history of disease after TACE. A previously published limited immunohistochemistry study showed that 74-80% of HCC tumors presented moderate-to-strong staining for PSMA, while completely negative staining was seen in only 4-26% of samples [11,19]. All studies showed PSMA expression in the neovascular structures [11,12,19].…”

Section: Discussionmentioning

confidence: 74%

“…However, as liver gluconeogenesis in well-differentiated HCC is comparable to normal, the sensitivity of [ 18 F]FDG PET for detecting HCC is not better than that of conventional imaging (50-70%) [2]. Therefore, other PET tracers based on lipid metabolism have been proposed for the detection of HCC, including [ 11 [3,2]. Similarly, [ 18 F]F-choline (which is a component of phosphatidylcholine, an essential element in cell membranes) has a similar sensitivity to [ 11 C]C-labeled acetate, ranging from 75 to 87% [3,2].…”

Section: Introductionmentioning

confidence: 99%

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[68 Ga]Ga-Prostate-Specific Membrane Antigen PET/CT: a novel method for imaging patients with hepatocellular carcinoma

Kunikowska

Cieślak

Gierej

et al. 2020

Eur J Nucl Med Mol Imaging

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Purpose Prostate-specific membrane antigen (PSMA) is not only highly expressed on the surface prostate cancer cells but is also elevated during angiogenesis in other cancer cell types, including hepatocellular carcinoma (HCC). This study aimed to evaluate the feasibility of using PET/CT imaging with [ 68 Ga]Ga-PSMA-11 in HCC and its impact on patient management. Methods Fifteen patients (13 men and two women; aged 55.6 ± 18.2 years) with HCC were enrolled in this prospective, singleinstitution study. All patients underwent contrast-enhanced MRI/CT, [ 68 Ga]Ga-PSMA-11 PET/CT, and histopathological verification of lesions. Results No radiopharmaceutical-related adverse events were noted. Visual interpretation showed increased accumulation of [ 68 Ga]Ga-PSMA-11 in all HCC patients. The tumor-to-liver ratio (TLR) was 3.6 ± 2.1, and the maximal standardized uptake value (SUV max) was 13.5 ± 7.1. There were no significant differences in the SUVs or TLR between newly diagnosed and recurrent patients. No statistically significant relationship was found between serum concentration of tumor markers (i.e., AFP, CA 19-9, CEA) and PET parameters. Results of the [ 68 Ga]Ga-PSMA-11 PET/CT changed the treatment strategy in five (33%) patients. PSMA staining showed visible heterogeneity in terms of intensity and distribution: the reaction was weak and only observed in a few vessels in pseudoglandular patterns of HCC, while it was homogeneously strong, with some hot spots, in trabecular patterns of HCC. Conclusion [ 68 Ga]Ga-PSMA-11 PET/CT can detect PSMA expression in vivo in patients with HCC and is useful for guiding treatment strategies. Further investigation of the clinical utility of this method in HCC is warranted.

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“…However, most patients with HCC are diagnosed during the middle and advanced stages, during which traditional radiotherapy and chemotherapy have limited clinical benefit. This is primarily due to high rates of recurrence and metastasis (4), therefore, it is important to identify novel diagnostic and prognostic markers to aid earlier intervention.…”

Section: Introductionmentioning

confidence: 99%

High‑throughput sequencing‑based analysis of gene expression of hepatitis B virus infection‑associated human hepatocellular carcinoma

et al. 2020

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Hepatitis B virus (HBV) infection is a critical factor for the initiation and progression of hepatocellular carcinoma (HCC). Gene expression profiles for HBV-associated HCC may provide valuable insight for the diagnosis and treatment of this type of HCC. The present study aimed to screen the differential genes in human HCC tissues based on high-throughput sequencing and to predict the potential therapeutic targets. Total mRNA was extracted from human HCC tissues and paracancerous tissues and sequenced using the Hiseq4000 sequencing platform. Differential gene expressions were screened and further analyzed using quantitative PCR and immunohistochemistry. A total of 2,386 differentially expressed genes were screened. Of these, 1119 were upregulated and 1,267 were downregulated in paracancerous tissues compared with tumor tissues. Gene Ontology term analysis demonstrated that differentially expressed genes were involved in carboxylic acid catabolism, monocarboxylic acid metabolic processes and α-amino acid metabolic processes. Molecular functional analysis revealed that the differentially expressed genes functioned in oxidoreductase activity, for example acting on CH-OH group of donors and permitting identical protein binding, anion binding, coenzyme binding and monocarxylic acid transporter activity. The Kyoto Encyclopedia of Genes and Genomes analysis reported that the differentially expressed genes were primarily concentrated in 20 signaling pathways, such as valine, leucine and leucine degradation, retinol metabolism and the cell cycle. Differential expression of proteins regulating the cell cycle, including stratifin, cyclin B1 and cyclin-dependent kinase 1, were significantly higher in tumor tissue compared with those in paracancerous tissue at both the mRNA and protein levels. These results were consistent with those obtained from high-throughput sequencing, indicating the reliability of the high-throughput sequencing. Together, these results identified differentially expressed genes and predicted the subsequent signaling pathways, which may be involved in the occurrence and development of HCC. Therefore, the present study may provide novel implications in the therapeutic and diagnosis of HCC.

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Expression of Prostate-Specific Membrane Antigen in Tumor-Associated Vasculature Predicts Poor Prognosis in Hepatocellular Carcinoma

Cited by 48 publications

References 33 publications

Upregulation of annexin A1 protein expression in the intratumoral vasculature of human non–small-cell lung carcinoma and rodent tumor models

Upregulation of annexin A1 protein expression in the intratumoral vasculature of human non–small-cell lung carcinoma and rodent tumor models

[68 Ga]Ga-Prostate-Specific Membrane Antigen PET/CT: a novel method for imaging patients with hepatocellular carcinoma

High‑throughput sequencing‑based analysis of gene expression of hepatitis B virus infection‑associated human hepatocellular carcinoma

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