Analysis of various <scp>ATP</scp>‐binding cassette transporters revealed quantification of <scp>ABCB4</scp> as a potential diagnostic tool in primary sclerosing cholangitis (<scp>PSC</scp>)
Bibliographic record
Abstract
AIMS: ATP-binding cassette transporters are important proteins in regulating bile constituent transport between hepatocytes and the bile canalicular system. Dysfunctional transporters lead to accumulation of toxic bile components within hepatocytes or the biliary system, known as cholestasis, resulting in liver damage. It has been previously reported that two particular ATP-binding cassette transporters, ABCB4 and ABCB11, have altered expression in patients with primary sclerosing cholangitis (PSC). Interested in further analysis of expression patterns of ATP-binding cassette transporters in PSC patients, we investigated liver samples from 201 patients, including 43 patients with PSC and 51 patients with primary biliary cholangitis patients (PBC). In addition to ABCB4 and ABCB11, we also included other ATP-binding cassette transporters, to determine if upregulation of ABCB4 and ABCB11 is specifically found in the liver of patients with PSC. METHODS AND RESULTS: Retrospectively, formalin-fixed and paraffin-embedded liver biopsies, resections, and explants were selected to investigate the expression of ABCB1, ABCB4, ABCB11, ABCG5/8, and FXR1 using nanoString nCounter and immunohistochemistry for validation of differently expressed transporters seen in PSC liver samples in comparison to non-PSC liver specimens. Strikingly, ABCB4 was the only ATP-binding cassette transporter showing increased gene and protein expression in hepatocytes of PSC livers when compared to non-PSC liver specimens. Furthermore, ABCB4 protein expression also correlated with disease stage in PSC. CONCLUSION: Our study concluded that altered ABCB4 expression is specifically seen in liver specimens of PSC patients. Therefore, quantitative ABCB4 analysis may be an additional useful tool for the histopathological diagnosis of PSC to distinguish this entity from other cholangiopathies.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.003 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".