Improving pathological early diagnosis and differential biomarker value for hepatocellular carcinoma via RNAscope technology

Bakheet, Ahmed Musa Hago; Zhao, Chang; Chen, Jianning; Zhang, Jing‐yue; Huang, Junting; Du, Yu; Gong, Li‐ping; Bi, Yanlan; Shao, Chun-Kui

doi:10.1007/s12072-019-10006-z

Cited by 17 publications

(18 citation statements)

References 26 publications

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“…In our study, the expression of the selected molecules in skin cancers are supported by RNAscope Hiplex assay, demonstrating the advantages of the assay. RNAscope detection is more suitable than IHC in precancerous dysplastic nodules, helping early monitoring and diagnosis for patients with high risk diseases (Bakheet et al 2020). Additionally, the absolute quantification of the target genes from ddPCR analysis supports the possibility of quantification using RNAscope assay.…”

Section: Discussionmentioning

confidence: 95%

“…Our results suggest RNAscope Hiplex assay to be quantitative, sensitive and high-resolution in detecting L-R interactions. RNAscope detection is more suitable than IHC in precancerous dysplastic nodules, helping early monitoring and diagnosis for patients with high risk of diseases (Bakheet et al, 2020). Additionally, our results from the absolute quantification of the target genes from ddPCR analysis (using adjacent tissue sections of the same tissue blocks) suggests that the RNAscope is able to accurately measure the expression of L-R pairs at the tissue level.…”

Section: Discussionmentioning

confidence: 99%

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Spatial analysis of ligand-receptor interaction in skin cancer at genome-wide and single-cell resolution

Trân

Yoon

Teoh

et al. 2020

Preprint

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The ability to study cancer-immune cell communication across the whole tumor section without tissue dissociation is important to understand molecular mechanisms of cancer immunotherapy and drug targets. Current experimental methods such as immunohistochemistry allow researchers to investigate a small number of cells or a limited number of ligand-receptor pairs at tissue scale with limited cellular resolution. In this work, we developed a powerful experimental and analytical pipeline that allows for the genome-wide discovery and targeted validation of cellular communication. By profiling thousands of genes, spatial transcriptomic and single-cell RNA sequencing data show genes that are possibly involved in interactions. The expression of the candidate genes could be visualized by single-molecule in situ hybridization and droplet digital PCR. We developed a computational pipeline called STRISH that enables us to quantitatively model cell-cell interactions by automatically scanning for local expression of RNAscope data to recapitulate an interaction landscape across the whole tissue. Furthermore, we showed the strong correlation of microscopic RNAscope imaging data analyzed by STRISH with the gene expression values measured by droplet digital PCR. We validated the unique ability of this approach to discover new cell-cell interactions in situ through analysis of two types of cancer, basal cell carcinoma and squamous cell carcinoma. We expect that the approach described here will help to discover and validate ligand receptor interactions in different biological contexts such as immune-cancer cell interactions within a tumor.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Spatial analysis of ligand-receptor interaction in skin cancer at genome-wide and single-cell resolution

Trân

Yoon

Teoh

et al. 2020

Preprint

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“…Tumor tissue for PCR testing was removed in tumors that were not represented in tissue microarrays, as described in a previous study (18). The Roche The stained slides of each specimen were examined using the RNAscope scoring system, as described in previous studies (19,20). High-risk HPV subtypes were evaluated on all ECAs in the tissue microarray that had su cient tissue to allow scoring (n = 200).…”

Section: Hpv Genotypementioning

confidence: 99%

Prognostic nomogram for patients with invasive endocervical adenocarcinoma incorporating HPV E6/E7 mRNA in situ hybridization and clinical characteristics

Liu¹,

Chen²,

Yan³

et al. 2020

Preprint

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Background: Human papillomavirus (HPV) E6/E7 mRNA in situ hybridization (HPV E6/E7 RNAscope) appears to be a sensitive and specific method. We aimed to examine the diagnostic and prognostic utility of this technique in endocervical adenocarcinoma (ECA) and build a useful prognostic nomogram model using this approach. Methods: The model was constructed from a retrospective study of 200 patients with ECA who had undergone surgery at Sun Yat-sen University Cancer Center between 2010 and 2014. The model's predictive efficiency and discriminative capability were defined by a concordance index (C-index) and calibration curve. Results: The overall sensitivity and specificity of HPV E6/E7 RNAscope for distinguishing HPV-associated adenocarcinoma (HPVA) from non HPV-associated adenocarcinoma (NHPVA) in the whole cohort were 75.8% and 80%, respectively, compared to 60.2% and 90.0% for p16 immunohistochemistry, 80.5% and 80.0% for HPV DNA, and 63.3% and 50% for HPV genotype. The independent factors derived from multivariable analysis of the whole cohort to predict overall survival (OS) were age, lymphovascular invasion (LVI), lymph node involvement (LNI), and HPV E6/E7 RNAscope, which were all incorporated into the nomogram with (nomogram B) or without (nomogram A) FIGO stage and treatment. The C-index of nomogram A for predicting OS was 0.825 (p = 0.002 and p < 0.001), which was significantly higher than the C-index for FIGO stage (0.653) and treatment (0.578). No significant difference occurred between nomograms A (0.825) and B (0.836). Furthermore, a risk stratification system was established to accurately stratify patients with ECA into two subgroups with significantly different prognosis. Conclusions: HPV E6/E7 RNAscope is highly specific for ECA, and the proposed nomogram using HPV E6/E7 RNAscope showed more accurate outcome in terms of prognosis in patients with ECA.

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“…GPC3 staining was found to be negative or focally weakly expressed in HCC precursor lesions, but diffuse GPC3 staining is observed in the majority of HCCs (10). A growing body of evidence supports GPC3 as a novel biomarker for HCC, and its protein expression is associated with poor prognosis of patients with HCC (11,12). However, the sensitivity and specificity of GPC3 must be further optimized.…”

Section: Introductionmentioning

confidence: 99%

Abnormal expression of HNRNPA3 in multistep hepatocarcinogenesis

et al. 2020

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Hepatocarcinogenesis is a multistep process involving progression from cirrhosis, to low-grade dysplastic nodule, to high-grade dysplastic nodule (HGDN) and, eventually, to hepatocellular carcinoma (HCC). Early detection of HCC is challenging as the differential diagnosis between HGDN and early HCC (eHCC) is difficult. The aim of the present study was to identify a novel biomarker to specifically differentiate between HGDN and eHCC, which may facilitate early diagnosis of HCC. Immunohistochemistry was performed to determine the expression of heterogeneous nuclear ribonucleoprotein A3 (HNRNPA3) in cirrhosis, dysplastic nodules (DNs), well-differentiated HCC and progressed HCC. The staining was evaluated by assigning a staining intensity score of 0–3 and a percentage of positively stained cells score of 0–4. Receiver operator characteristic (ROC) curve analysis was used to assess the ability of HNRNPA3 expression to differentiate between DNs and HCC. HNRNPA3 expression increased in a stepwise trend in non-tumor hepatic tissue, DNs, eHCC and progressed HCC. ROC curves revealed that HNRNPA3 expression could be used to differentiate between HGDN and eHCC, particularly in combination with glypican 3 (GPC3), with a specificity of 100%. Moreover, HNRNPA3 expression was associated with HCC differentiation. In addition, high expression of HNRNPA3 was found to be associated with poor survival rates in patients with HCC. These findings demonstrated that HNRNPA3 combined with GPC3 is a helpful diagnostic biomarker in the differential diagnosis during the multistep process of hepatocarcinogenesis, particularly in the differential diagnosis between HGDN and eHCC. To the best of our knowledge, this is the first study to report the significance of HNRNPA3 in hepatocarcinogenesis and its potential role in carcinogenesis.

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Improving pathological early diagnosis and differential biomarker value for hepatocellular carcinoma via RNAscope technology

Cited by 17 publications

References 26 publications

Spatial analysis of ligand-receptor interaction in skin cancer at genome-wide and single-cell resolution

Spatial analysis of ligand-receptor interaction in skin cancer at genome-wide and single-cell resolution

Prognostic nomogram for patients with invasive endocervical adenocarcinoma incorporating HPV E6/E7 mRNA in situ hybridization and clinical characteristics

Abnormal expression of HNRNPA3 in multistep hepatocarcinogenesis

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