KEY POINTS
- The study combined TCGA data with an independent institutional cohort to investigate CAVIN3 as a potential biomarker of radiotherapy response in cervical cancer. Of 133 TCGA patients identified as having received radiotherapy, 57 had evaluable imaging response data and 43 had complete survival data; the validation cohort included 66 patients treated with first-line external-beam radiotherapy.
- CAVIN3 expression was significantly lower in cervical cancer than in normal cervical tissue in both datasets (p=0.019 in TCGA; p=0.002 in the institutional cohort). The ability to distinguish cancer from normal tissue yielded AUCs of 0.894 and 0.947, respectively.
- Among the 57 TCGA patients with response assessment, objective response was 88.2% (30/34) in tumors with low CAVIN3 expression versus 56.5% (13/23) with high expression - an absolute difference of 31.7 percentage points (95% CI 11.7–52.3; p=0.006). Low expression corresponded to approximately 5.8-fold greater odds of response.
- Survival showed the same direction. In the TCGA survival subset, median overall survival was not reached with low CAVIN3 versus 31.8 months with high expression (p=0.043). High expression remained independently associated with mortality in multivariable analysis (HR 13.67, 95% CI 1.47–126.76; p=0.021), although the extremely wide confidence interval reflects the small sample.
- In the 66-patient validation cohort, only 10 patients had high CAVIN3 expression. Median progression-free survival was 59.9 months with low expression versus 9.8 months with high expression, and low expression remained associated with lower progression risk after adjustment (HR 0.37, 95% CI 0.16–0.89; p=0.025).
- Overall survival was also substantially worse in the high-expression validation group: median survival was 17.45 months versus not reached. High CAVIN3 remained independently associated with mortality (HR 3.20, 95% CI 1.33–7.69; p=0.009), while tumor diameter ≥4.8 cm was another independent adverse factor.
- Transcriptomic analyses linked high CAVIN3 expression to extracellular-matrix organization and remodeling, cell adhesion, integrin β1 signalling, growth and differentiation pathways. The authors propose that this matrix-associated phenotype may contribute to radioresistance, but this mechanism was inferred from enrichment analysis rather than experimentally demonstrated.
CLINICAL TAKEAWAY
CAVIN3 is an interesting candidate biomarker for cervical cancer radiosensitivity: low-expression tumors showed both a substantially higher response rate and longer progression-free survival in two datasets. But this is not ready for treatment selection - the survival cohorts were small, only 10 validation patients had high expression, treatment details were heterogeneous, and predictive utility has not been tested prospectively.