Study on the Expression Level of CAVIN3 Gene and the Prognosis of Radiotherapy in Patients with Cervical Cancer

This study aims to investigate the expression of CAVIN3 in cervical cancer, its effect on radiotherapy outcomes, and its potential molecular mechanisms.

The GEPIA2 database was used to screen genes that may affect cervical cancer prognosis. Then, we analyzed 133 cervical cancer patients from the TCGA database who received radiotherapy to evaluate CAVIN3 gene expression and function. Receiver operating characteristic (ROC) curves and Cox regression models were employed to assess the diagnostic value of CAVIN3 and its association with radiotherapy outcomes. GSEA, GO, and KEGG databases were used to perform pathway enrichment analysis of CAVIN3-related signaling pathways. We also collected pretreatment biopsy specimens from 66 patients who were subsequently treated with radiotherapy from our center to validate the findings from the database analysis.

In the TCGA database, CAVIN3 expression was significantly lower in cervical cancer tissues than in normal cervical tissues (p = 0.019), a finding that was independently corroborated in our own cohort (p = 0.002). Receiver operating characteristic analysis yielded area-under-the-curve values of 0.894 for the TCGA RNA-seq data and 0.947 for our center, underscoring the gene's potential diagnostic utility. Next, we stratified cervical cancer patients who received radiotherapy by intratumoral CAVIN3 levels. Notably, the low-expression group consistently showed better treatment outcomes. In the TCGA cohort, high CAVIN3 expression was associated with significantly shorter median overall survival (mOS, 31.8 months versus not reached within follow-up; p = 0.043). This pattern was confirmed in our validation cohort, where high CAVIN3 expression predicted markedly inferior median progression-free survival (mPFS, 9.8 vs. 59.9 months; p < 0.05) and mOS (17.45 months vs. not reached; p < 0.05). Consistent with these survival differences, the objective response rate to radiotherapy was lower in the high-expression group than in the low-expression group (56.5% vs. 88.2%, p = 0.006), revealing better radiotherapy response among tumors with low CAVIN3 expression. Enrichment analysis revealed that the high CAVIN3 expression group was primarily enriched in pathways related to extracellular matrix formation and remodeling, extracellular matrix-cell membrane interactions, cell adhesion and migration, integrin β1 signaling, and the regulation of cell growth, differentiation, and apoptosis. Together, these functions indicate a more differentiated, matrix-attached phenotype that can promote radioresistance. Conversely, low CAVIN3 expression likely reflects a poorly differentiated state with diminished matrix interaction, which renders the tumor more vulnerable to radiation.

CAVIN3 downregulation is a frequent event in cervical cancer and may contribute to tumor susceptibility. Paradoxically, within tumors, low expression of CAVIN3 is associated with an enhanced response to radiotherapy, likely stemming from the underlying phenotype characterized by poor differentiation and heightened radiosensitivity. Therefore, CAVIN3 expression levels are correlated with cervical cancer development and the radiotherapy response of cervical cancer patients.