Radiotherapy (RT) as a preoperative or postoperative adjuvant or primary treatment is the most common management modality for locally advanced cervical cancer. Radioresistance of tumor cells remains a major therapeutic problem. Consequently, we aimed to explore if the stem cell biomarkers SOX2 and OCT4 protein could be used to predict radioresistance in patients with locally advanced cervical squamous cell carcinoma (LACSCC). These 132 patients were divided into two groups (radiation-resistant and radiation-sensitive groups) according to progress-free survival (PFS). Using pretreatment paraffin-embedded tissues, we evaluated SOX2 and OCT4 expression using immunohistochemical staining. The percentage of overexpression of SOX2 and OCT4 in the radiation-resistant group was much higher than that in the radiation-sensitive group ( p<0.001 and p <0.001, respectively). The patients with high expression of SOX2 and OCT4 showed a shorter PFS than those with low expression. Our study suggests that the expression of SOX2 and OCT4 in tumor cells indicates resistance to radiotherapy and that these two factors were important predictors of poor survival in patients with LACSCC (hazard ratio [95% CI], 2.294 [1.013, 5.195] and 2.300 [1.050, 5.037], respectively; p=0.046 and p=0.037, respectively).

Background and purpose: We evaluated the relationship between patient-, tumor-, and treatment-related features and radiation-induced lymphopenia (RIL) and evaluated the correlation between RIL and survival outcome in NPC patients to help improve the treatment strategy.Methods: This retrospective study included 374 patients with stage II-IVa NPC who had been treated with definitive RT and were enrolled from 2004 to 2015; The associations between the G3–4 RIL (absolute lymphocyte count, ALC < 0.5 × 10⁹cells/L) during RT and patient-, tumor-, and treatment-related factors were assessed using Cox regression analyses. The correlation between ALC nadir and survival was examined using a Kaplan-Meier analysis, compared with the log-rank test, and confirmed by a Cox proportional hazards analysis.Results: In the multivariate analysis, lower baseline ALC and intensity modulated radiation therapy (IMRT) (vs. 2 dimensional-conformal radiation therapy,2D-CRT) were identified as 2 independent factors that were associated with G3–4 RIL. In the multivariate survival analysis, patients with G3–4 ALC nadir had longer local recurrence-free survival durations (LRFS) (vs. G0–2 nadir, HR = 0.548,P = 0.005) and longer progression-free survival durations (PFS) (vs. G0–2 nadir, HR = 0.676,P = 0.022), while patients with G4 ALC nadir had a shorter distant-metastasis-free survival duration (DMFS) (vs. G0–2 nadir, hazard ratio [HR] = 2.567,P = 0.037).Conclusions: In the study, lymphopenia during RT were affected by baseline ALC and RT modality independently. Moreover, G3–4 ALC nadir was independently linked with longer PFS and LRFS durations, while G4 ALC nadir was independently linked with a shorter DMFS duration.

Background: Radiotherapy (RT) is the standard treatment for nasopharyngeal carcinoma (NPC). However, due to individual differences in radiosensitivity, biomarkers are needed to tailored radiotherapy to cancer patients. However, comprehensive genome-wide radiogenomic studies on them are still lacking. The aim of this study was to identify genetic variants associated with radiotherapy response in patients with NPC. Methods: This was a large‑scale genome-wide association analysis (GWAS) including a total of 981 patients. 319 individuals in the discovery stage were genotyped for 688,783 SNPs using whole genome-wide screening microarray. Significant loci were further genotyped using MassARRAY system and TaqMan SNP assays in the validation stages of 847 patients. This study used logistic regression analysis and multiple bioinformatics tools such as PLINK, LocusZoom, LDBlockShow, GTEx, Pancan-meQTL and FUMA to examine genetic variants associated with radiotherapy efficacy in NPC. Results: After genome-wide level analysis, 19 SNPs entered the validation stage (P < 1 × 10^− 6), and rs11130424 ultimately showed statistical significance among these SNPs. The efficacy was better in minor allele carriers of rs11130424 than in major allele carriers. Further stratified analysis showed that the association existed in patients in the EBV-positive, smoking, and late-stage (III and IV) subgroups and in patients who underwent both concurrent chemoradiotherapy and induction/adjuvant chemotherapy. Conclusion: Our study showed that rs11130424 in the CACNA2D3 gene was associated with sensitivity to radiotherapy in NPC patients. Trial registration number: Effect of genetic polymorphism on nasopharyngeal carcinoma chemoradiotherapy reaction, ChiCTR-OPC-14005257, Registered 18 September 2014, http://www.chictr.org.cn/showproj.aspx?proj=9546.