A Novel Oncogenic and Drug-Sensitive KIF5B-NTRK1 Fusion in Lung Adenocarcinoma
Bibliographic record
Abstract
We present a case of a lung adenocarcinoma patient harboring a novel kinesin family member 5B (KIF5B)-NTRK1 gene fusion that responds well to entrectinib. Moreover, KIF5B-NTRK1 gene chimera has been shown to be an oncogene, activating both the MAPK and PI3K/AKT signaling pathways. The biopsy sample was analyzed using various methods such as hematoxylin–eosin staining (HE), immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS) based on a 1267-gene panel. Additionally, human lung adenocarcinoma cell lines A549 and H1755 were used to obtain a stable expression of chimera gene products. The cell proliferation was confirmed using CCK8 and adhesion-dependent colony formation assay. Cell invasion was confirmed using the transwell invasion assay. The protein levels of the MAPK and PI3K/AKT signaling pathways were assessed using Western blotting. The patient, a 66-year-old Chinese male, was diagnosed with adenocarcinoma (stage IVB) located in the upper lobe of the left lung. NGS analysis identified a novel KIF5B-NTRK1 fusion gene, which was further confirmed by FISH and IHC analyses. As a first-line therapy, entrectinib was administered to the patient at a dose of 600 mg once daily, resulting in a partial response. The patient’s progression-free survival (PFS) has now been more than 12 months, and no serious toxicities have been observed so far. Furthermore, stable KIF5B-NTRK1-expressing cells were generated and the experimental results demonstrate enhanced proliferation abilities, along with increased levels of proteins involved in the MAPK and PI3K/AKT signaling pathways. Our study reports a novel KIF5B-NTRK1 genetic rearrangement that supports favorable responses to entrectinib. Moreover, in vitro experiments showed that the fusion gene could exert oncogenic properties by activating the MAPK and PI3K/AKT signaling pathways. To summarize, our findings broaden the spectrum of NTRK gene fusions in the context of lung adenocarcinoma.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.003 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".