Frontiers in Public Health · Oct 31, 2026
Dietary Fiber, Insulin Resistance, Rectal Microbial Profiles, and Endometrial Cancer Transcriptomics: Parallel Secondary Analyses with HEC-1-A RT-qPCR Data
By He Wan, Mengmeng Wu, Hui Chen et al.
Background: Endometrial cancer (EC) is associated with obesity and metabolic dysfunction, but population-level dietary associations and tumor transcriptomic context are not fully characterized. We conducted parallel secondary analyses of public datasets and an HEC-1-A RT-qPCR experiment; the public datasets were not patient-matched. Methods: GSE300407 single-nucleus profiles compared normal-weight and obese endometrioid EC specimens; GSE17025 compared endometrioid cancers with nonmalignant endometria; NHANES 2013–2018 was used to examine dietary fiber, carbohydrate, and total-sugar densities in relation to log-transformed HOMA-IR among adult women; and published PRJNA1036657 rectal microbiome summary estimates were reanalyzed. In HEC-1-A cells, HIF1A, MTOR, INSR, and IGF1R expression was measured by GAPDH-normalized RT-qPCR using the 2⁻ΔΔCt method under control, high-glucose, and high-glucose + insulin conditions. Results: After quality control, 47,494 nuclei from 13 GSE300407 donors (six normal-weight and seven obese) were retained. Seven epithelial genes met q < 0.05 and |log2 fold change| > 0.5, but none of five focal genes passed full-family correction. mTORC1 and glycolysis enrichment scores were negative, indicating enrichment toward the normal-weight end of the ranking; no donor-level lineage-program test or LIANA interaction passed Benjamini–Hochberg correction. In GSE17025, none of the five focal genes passed gene-level correction, although 35 of 50 Hallmark contrasts did. Among 2,774 NHANES women, associations of fiber, carbohydrate, and sugar density with HOMA-IR did not survive multiple-testing correction (ratios 0.984 per 5 g fiber, 1.064 per 50 g carbohydrate, and 1.011 per 25 g total sugar per 1,000 kcal; corresponding q values 0.448, 0.071, and 0.448). In the jointly adjusted rectal microbiome model, Buttiauxella agrestis A and predicted L-valine degradation had source-reported q values of 0.0353 and 0.00272, respectively. The HEC-1-A RT-qPCR experiment showed increased HIF1A, MTOR, and IGF1R expression and decreased INSR expression in the treatment groups; all treatment-versus-control comparisons had Holm-adjusted P < 0.01. Conclusions: These independent analyses are hypothesis-generating and do not establish links between diet, tumor biology, and clinical outcomes in the same individuals. The RT-qPCR results provide experimental transcript-level observations but do not establish protein activation or a causal link to the independent public-data findings.