1. The paper repeatedly uses “glycemic” (blood glucose-related) when the correct term is “glycomic” (glycan structure-related). This fundamental confusion (e.g., “glycemic revolution,” “glycemic dysregulation,” “glycemic signatures”) undermines scientific credibility. Was this a persistent editing oversight, or does it reflect a conceptual misunderstanding of the field?
2. Table 1 lumps ovarian, cervical, and endometrial cancers together under identical glycomic alterations. Given that cervical cancer is HPV-driven with distinct molecular pathogenesis versus the hormonal/epithelial origins of ovarian/endometrial cancers, what evidence supports that they share identical N-glycan branching and hypersialylation mechanisms? Where are the cancer type-specific data?
3. Section 3.1 states that glycoform-specific CA-125 achieves “diagnostic accuracy for ovarian cancer exceeding 95% specificity” citing reference [30] from 2021. Yet reference [30] is a review, not a primary study, and does not report this 95% figure. Please provide the primary source for this critical performance claim—no such specificity has been validated prospectively.
4. The conclusion states “advances progress over the next 2-3 years”. Given that FDA approval for diagnostic assays typically requires 5-7 years of prospective trials, what specific regulatory pathway (LDT vs. pre-market approval) and what ongoing trials support this unrealistic timeline?