Glycan Profiling Identifies Chondroitin-4-sulfate as a Biomarker for Platinum Response and Therapeutic Target in Ovarian Cancer
Bibliographic record
Abstract
For women with advanced ovarian cancer (OC), remission is typically achieved through surgery and combination chemotherapy, with duration largely dependent on tumor sensitivity to platinum-based drugs. Here, we show that tumor-associated glycosaminoglycans (GAGs) influence platinum drug efficacy in preclinical models of ovarian cancer. Due to the complexity of GAG biosynthesis and the involvement of multiple enzymes, traditional transcriptomic and proteomic approaches cannot accurately estimate their levels or correlation with patient response and survival. To address this, we quantitatively analyzed the full compositional profile of GAGs in OC patient-derived xenograft (PDX) models with known carboplatin sensitivity. Our results revealed a significant correlation between carboplatin resistance and high levels of the predominant GAG sequence, chondroitin-4-sulfate (C4S). Further investigation in cellular models demonstrated that high GAG expression reduces carboplatin uptake, DNA adduct formation, and tumor accumulation, whereas the opposite effect was observed for Triplatin, a GAG-targeting platinum agent. These trends were further validated in vivo, where treatment of OC PDX models with varying C4S levels confirmed that carboplatin efficacy decreases while Triplatin activity increases in tumors with high C4S expression. Based on these findings, we established a C4S cut-off score to predict tumor sensitivity, identifying a threshold above which tumors are likely to be carboplatin-resistant but Triplatin-sensitive. Analysis of patient tissue microarrays estimated that 40-83% of OC tumors, depending on subtype, exhibit high C4S expression. Collectively, these findings highlight the predictive power of C4S as a biomarker for platinum response and support the clinical evaluation of Triplatin as a targeted treatment for patients with carboplatin-resistant tumors expressing high levels of C4S.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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 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".