This study aims to evaluate the efficacy of chemoradiotherapy for advanced cervical cancer using heat shock protein 70 (HSP70) combined with multimodal MRI. The protein expressions of HSP70 in biopsy specimens obtained from 101 patients with cervical cancer were detected by immunohistochemistry. Plain MRI scan, DWI, DCE-MR, and MRS were performed before and after a period of 6 months of chemoradiotherapy. All patients were assigned into the complete response (CR) and partial response (PR) groups. HSP70 protein expression, tumor diameter, and tumor volume were lower in the CR group than in the PR group. The rate of tumor shrinkage, relative positive enhancement integral (rPEI), relative maximum slope of decrease (rMSD), relative signal enhancement ratio at 60 s (rSER ) and maximum SER (rSER ), mean apparent diffusion coefficient (ADC ) and minimum ADC value (ADC ) values in the CR group were higher than those in the PR group. Tumor diameter and volume, rSER and rSER were reduced after chemoradiotherapy, while rMSD, rSER , time to peak (TTP), ADC and ADC were higher after the treatment. The receiver operating characteristic (ROC) curves indicated that HSP70 expression, tumor diameter, rPEI, ADC and Cho peak showed the better chemoradiotherapy efficacy. Our data demonstrates that HSP70 protein combined with multimodal MRI may accurately evaluate the chemoradiotherapy efficacy of patients with advanced cervical cancer. The recurrence of cervical cancer significantly decreased in patients with negative expression of HSP70 and HSP70 protein detection provides potential therapy for the prevention, diagnosis, and prognosis of cervical cancer.

The phosphorylation of EGFR Thr654 is required for nuclear EGFR importing, and our previous study has shown that pEGFR Thr654 is an independent prognostic factor for the low survival rate of patients with cervical squamous carcinoma. Now, we aim to examine the role of pEGFR Thr654 in the activation of DNA-PK and radio resistance. Either CaSki or HeLa cells were exposed to a dose of 4 Gy with a 6 MV Xray in the presence or absence of Cetuximab or Gefitinib, then EGFR, pEGFR Thr654 , DNA-PKcs and pDNA-PK Thr2609 levels were determined using a western blot. DNA damage was quantified with gH2AX foci analysis and the response of CaSki and HeLa cells to irradiation was determined using a colony formation assay. In CaSki and HeLa cells, irradiation induced nuclear EGFR accumulation, and pEGFR Thr654 and pDNA-PK Thr2609 levels were both significantly increased. Cetuximab pre-treatment significantly reduced the expression of pEGFR Thr654 and pDNA-PK Thr2609 and enhanced the gH2AX foci per cell and sensitivity enhancement ratio in CaSki cells. Gefitinib pre-treatment had a similar but weaker effect. In HeLa cells, similar effects of Cetuximab and Gefitinib on pEGFR Thr654 and pDNA-PK Thr2609 were observed, and no significant difference was found. We found that Cetuximab had a better effect than Gefitinib on attenuating the radio resistance in cervical squamous carcinoma cells via inhibiting pEGFR Thr654 -mediated nuclear EGFR transport and related DNA-PK T2609 -mediated DNA repair. However, in adenocarcinoma cells, both EGFR-targeted drugs had no remarkable effects on the radio sensitivity.Taken together, radiotherapy combined with Cetuximab may be a promising strategy to improve the therapeutic gain for cervical squamous carcinoma patients.