Mutual communication between radiosensitive and radioresistant esophageal cancer cells modulates their radiosensitivity.

Radiotherapy is an important treatment modality for patients with esophageal cancer; however, the response to radiation varies among different tumor subpopulations due to tumor heterogeneity. Cancer cells that survive radiotherapy (i.e., radioresistant) may proliferate, ultimately resulting in cancer relapse. However, the interaction between radiosensitive and radioresistant cancer cells remains to be elucidated. In this study, we found that the mutual communication between radiosensitive and radioresistant esophageal cancer cells modulated their radiosensitivity. Radiosensitive cells secreted more exosomal let-7a and less interleukin-6 (IL-6) than radioresistant cells. Exosomal let-7a secreted by radiosensitive cells increased the radiosensitivity of radioresistant cells, whereas IL-6 secreted by radioresistant cells decreased the radiosensitivity of radiosensitive cells. Although the serum levels of let-7a and IL-6 before radiotherapy did not vary significantly between patients with radioresistant and radiosensitive diseases, radiotherapy induced a more pronounced decrease in serum let-7a levels and a greater increase in serum IL-6 levels in patients with radioresistant cancer compared to those with radiosensitive cancer. The percentage decrease in serum let-7a and the percentage increase in serum IL-6 levels at the early stage of radiotherapy were inversely associated with tumor regression after radiotherapy. Our findings suggest that early changes in serum let-7a and IL-6 levels may be used as a biomarker to predict the response to radiotherapy in patients with esophageal cancer and provide new insights into subsequent treatments.

Efficacy of apatinib+radiotherapy vs radiotherapy alone in patients with advanced multiline therapy failure for non small cell lung cancer with brain metastasis.

OBJECTIVE: Lung cancer is the leading cause of cancer-associated mortality worldwide. Central nervous system (CNS) metastasis is a prevalent and serious complication. The most common treatment for brain metastasis (BM) is still radiation therapy (RT). An increasing number of drugs have been shown to have intracranial activity or to sensitize tumours to radiotherapy. METHODS: Consecutive advanced multiline therapy failure in patients with non-small-cell lung cancer (NSCLC) with BM at the authors' hospital were retrospectively reviewed. Eligible patients were divided into two groups: Apatinib+RT group and RT group. Intracranial progression-free survival (PFS) and overall survival (OS) were analysed using the Kaplan-Meier method. RESULTS: The median intracranial PFS for the RT group and Apatinib+RT group was 5.83 months and 11.81 months (p = 0.034). The median OS for the RT group and Apatinib+RT group was 9.02 months and 13.62 months (p = 0.311). The Apatinib+RT group had a better intracranial PFS, but there were no significant differences between the two arms in OS. The Apatinib+RT group had significantly reduced symptoms caused by BM. CONCLUSION: RT combined with apatinib could help to control intracranial metastases. The Apatinib+RT group had significantly reduced symptoms caused by BM and improved quality of life for patients, the safety of the two treatments was similar. ADVANCES IN KNOWLEDGE: Here, we propose that RT combined with apatinib can significantly relieve brain symptoms and tolerate side-effects without affecting OS in patients with BM following failure of multiline therapy for NSCLC. Of course, this paper is a retrospective origin study, and more powerful evidence is needed to demonstrate.

Direct Dose Prediction With Deep Learning for Postoperative Cervical Cancer Underwent Volumetric Modulated Arc Therapy.

PURPOSE: To predict the voxel-based dose distribution for postoperative cervical cancer patients underwent volumetric modulated arc therapy using deep learning models. METHOD: A total of 254 patients with cervical cancer received volumetric modulated arc therapy in authors' hospital from January 2018 to September 2021 were enrolled in this retrospective study. Two deep learning networks (3D deep residual neural network and 3DUnet) were adapted to train (203 cases) and test (51 cases) the feasibility and effectiveness of the prediction method. The performance of deep learning models was evaluated by comparing the results with those of treatment planning system according to metrics of dose-volume histogram of target volumes and organs at risk. RESULTS: The dose distributions predicted by deep learning models were clinically acceptable. The automatic dose prediction time was around 5 to 10 min, which was about one-eighth to one-tenth of the manual optimization time. The maximum dose difference was observed in D98 of rectum with a | δD| of 5.00 ± 3.40% and 4.88 ± 3.99% for Unet3D and ResUnet3D, respectively. The minimum difference was observed in the D2 of clinical target volume with a |δD| of 0.53 ± 0.45% and 0.83 ± 0.45% for ResUnet3D and Unet3D, respectively. CONCLUSION: The 2 deep learning models adapted in the study showed the feasibility and reasonable accuracy in the voxel-based dose prediction for postoperative cervical cancer underwent volumetric modulated arc therapy. Automatic dose distribution prediction of volumetric modulated arc therapy with deep learning models is of clinical significance for the postoperative management of patients with cervical cancer.

Infiltrating T-cell abundance combined with EMT-related gene expression as a prognostic factor of colon cancer.

EMT-related gene expression reportedly exhibits correlation with the anti-tumor immunity of T cells. In the present study, we explored the factors that might affect the efficacy of immunotherapy in colon cancer with treatment. In this regard, RNA-seq and clinical data of 469 colon cancer samples derived from the Cancer Genome Atlas (TCGA) database were used to calculate infiltrating T-cell abundance (ITA), to illustrate a pathway enrichment analysis, and to construct Cox proportional hazards (CPH) regression models. Subsequently, the RNA-seq and clinical data of 177 colon cancer samples derived from the GSE17536 cohort were used to validate the CPH regression models. We found that ITA showed correlation with EMT-related gene expression, and that it was not an independent prognostic factor for colon cancer. However, upon comparison of two groups with the same ITA, higher EMT expression helped predicted a worse prognosis, whereas a higher ITA could help predict a better prognosis upon comparison of two groups with the same EMT. Additionally, seven genes were found to be statistically related to the prognosis of patients with colon cancer. These results suggest that the balance between ITA and EMT-related gene expression is conducive to the prognosis of patients with colon cancer, and TPM1 is necessary to further explore the common target genes of immune checkpoint blockade.

Identification and Mechanism of the PD-1/PD-L1 Genomic Signature SORL1 as Protective Factor in Bladder Cancer.

Background: Immunotherapy has recently shown remarkable efficacy for advanced bladder cancer patients. Accordingly, identifying a biomarker associated with the programmed cell death protein 1 (PD-1)/its ligand (PD-L1) genomic signature to predict patient prognosis is necessary. Methods: In this study, we used mutation data and RNA-seq data of bladder cancer samples acquired from The Cancer Genome Atlas (TCGA) database to combine PD-1/PD-L1-associated mutational signatures with PD-1/PD-L1-associated differentially expressed genes (DEGs). Then, we performed a Kaplan-Meier analysis on the corresponding clinical data of the TCGA bladder urothelial carcinoma (BLCA) cohort to identify prognostic genes, and the results were validated using the GSE48075 cohort. The online platform UCSC Xena was used to analyze the relationship between the candidate genes and clinical parameters. We utilized the Human Protein Atlas (HPA) database to validate the protein expression levels. Then, correlation analysis, cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) analysis, and gene set enrichment analysis (GSEA) were used to clarify the mechanism. Results: We identified one prognostic gene, sortilin related receptor 1 (SORL1), whose downregulation was associated with a comparatively advanced BLCA stage. While further exploring this finding, we found that SORL1 expression was negatively correlated with PD-1/PD-L1 expression and M2 macrophage levels. Furthermore, we found that the downregulation of SORL1 expression was significantly associated with a higher epithelial-mesenchymal transition (EMT) score. Conclusion: We described a novel PD-1/PD-L1-associated signature, SORL1, that predicts favorable outcomes in bladder cancer. SORL1 might reduce immune suppression and inhibit the M2 macrophage-induced EMT phenotype of tumor cells.

Association of lung and heart dose with survival in patients with non-small cell lung cancer underwent volumetric modulated arc therapy.

BACKGROUND: Controversial conclusions had been reported in studies trying to confirm the impact of heart dose on overall survival (OS) reported in RTOG 0167 for non-small cell lung cancer (NSCLC) patients who underwent radiotherapy (RT). The purpose of this study is to investigate the association of lung and heart dosimetric parameters with OS in NSCLC patients treated by volumetric modulated arc therapy (VMAT). METHODS: Inoperable NSCLC patients treated by VMAT from March 2012 to December 2015 were retrospectively reviewed. OS and progression-free survival (PFS) were estimated with the Kaplan-Meier method. Univariate and multivariate analyses were conducted with Cox proportional hazards model. Multivariate model building was conducted using stepwise regression for variables with p-value smaller than 0.2 in the univariate analysis. RESULTS: There were 130 NSCLC patients enrolled in this study with a median age of 63 years (range from 34 to 82 y). The median prescription dose for these patients was 56 Gy (range 40-70 Gy) with a mean heart and lung dose of 14.8±8.5 Gy and 13.6±4.4 Gy, respectively. The rates of patients with above grade III radiation pneumonitis (RP) and fibrosis were 8.5% and 8.5%, respectively. The 2-year PFS and OS of these patients were 15.2% and 39.8%, with a median PFS and OS of 7.2 and 18.8 months, respectively. RP was correlated with OS (p=0.048) and lung V20 was associated with PFS (p=0.04) according to the univariate analysis. Multivariate analysis demonstrated that RP (HR 1.39, 95%CI 1.010-1.909, p=0.043) and heart V15 (HR 1.02, 95%CI 1.006-1.025 p=0.002) were progression factors of OS, and no factor was associated with PFS. CONCLUSIONS: RP and heart V15 were associated with OS for patients with stage III NSCLC who underwent VMAT. Heart and lung dosimetric parameters were highly correlated with each other, sparing of heart and lung should be considered equally during the treatment planning.

MicroRNA­301a targets WNT1 to suppress cell proliferation and migration and enhance radiosensitivity in esophageal cancer cells.

Esophageal cancer (EC) is one of the leading causes of death among malignancies. Radiotherapy for esophageal squamous cell carcinoma (ESCC) patients is limited by resistance to ionizing radiation (IR). An increasing body of evidence has demonstrated that aberrant expression of microRNA­301a (miR­301a) contributes to cancer progression and sensitivity to radiation. The aim of the present study was to investigate the exact functions and potential mechanisms of miR­301a in ESCC radioresistance. Initially, the miR­301a­transfected radioresistant ESCC cells KYSE­150R exhibited a decreased proliferation rate, and enhanced radiosensitivity and migration, whereas downregulation of miR­301a in radiosensitive KYSE­150 cells produced the opposite results. miR­301a regulates WNT1 expression at both the mRNA and protein levels. Furthermore, dual­luciferase reporter assays revealed that WNT1 was a target gene of miR­301a. In addition, the expression of miR­301a markedly affected the expression of Wnt/ß­catenin­related proteins such as ß­catenin and cyclin D1. Finally, overexpression of miR­301a inhibited epithelial­mesenchymal transition (EMT) conversion by directly targeting Snail and vimentin in radioresistant­ESCC cell lines; however, no inhibitory effects were exerted on Twist. Collectively, these results indicated that miR­301a increased the radiosensitivity and inhibited the migration of radioresistant­ESCC cells by targeting WNT1, thereby inactivating the Wnt/ß­catenin signaling pathway and EMT reversal. Thus, miR­301a may be a potential therapeutic target for the treatment of EC radioresistance.

Multidimensional correlation among plan complexity, quality and deliverability parameters for volumetric-modulated arc therapy using canonical correlation analysis.

A multidimensional exploratory statistical method, canonical correlation analysis (CCA), was applied to evaluate the impact of complexity parameters on the plan quality and deliverability of volumetric-modulated arc therapy (VMAT) and to determine parameters in the generation of an ideal VMAT plan. Canonical correlations among complexity, quality and deliverability parameters of VMAT, as well as the contribution weights of different parameters were investigated with 71 two-arc VMAT nasopharyngeal cancer (NPC) patients, and further verified with 28 one-arc VMAT prostate cancer patients. The average MU and MU per control point (MU/CP) for two-arc VMAT plans were 702.6 ± 55.7 and 3.9 ± 0.3 versus 504.6 ± 99.2 and 5.6 ± 1.1 for one-arc VMAT plans, respectively. The individual volume-based 3D gamma passing rates of clinical target volume (γCTV) and planning target volume (γPTV) for NPC and prostate cancer patients were 85.7% ± 9.0% vs 92.6% ± 7.8%, and 88.0% ± 7.6% vs 91.2% ± 7.7%, respectively. Plan complexity parameters of NPC patients were correlated with plan quality (P = 0.047) and individual volume-based 3D gamma indices γ(IV) (P = 0.01), in which, MU/CP and segment area (SA) per control point (SA/CP) were weighted highly in correlation with γ(IV) , and SA/CP, percentage of CPs with SA < 5 × 5 cm2 (%SA < 5 × 5 cm2) and PTV volume were weighted highly in correlation with plan quality with coefficients of 0.98, 0.68 and -0.99, respectively. Further verification with one-arc VMAT plans demonstrated similar results. In conclusion, MU, SA-related parameters and PTV volume were found to have strong effects on the plan quality and deliverability.

Evaluation of Tumor-Derived Exosomal miRNA as Potential Diagnostic Biomarkers for Early-Stage Non-Small Cell Lung Cancer Using Next-Generation Sequencing.

Purpose: To identify tumor-derived exosomal biomarkers that are able to discriminate between adenocarcinoma and squamous cell carcinoma (SCC) as a noninvasive method in the early diagnosis of non-small cell lung cancer (NSCLC).Experimental Design: Tumor-derived exosomes from the plasma of early-stage NSCLC patients were isolated. Exosomal miRNA profiling of 46 stage I NSCLC patients and 42 healthy individuals was performed using miRNA-seq to identify and validate adenocarcinoma- and SCC-specific miRNAs. The diagnostic accuracy of select miRNAs was tested further with an additional 60 individuals.Results: There were 11 and 6 miRNAs expressed at remarkably higher levels, 13 and 8 miRNAs expressed at lower levels in adenocarcinoma and SCC patients, respectively, compared with healthy volunteers. Distinct adenocarcinoma- and SCC-specific exosomal miRNAs were validated. The reliability of miRNA-seq data was verified with several demonstrated diagnostic potential miRNAs for NSCLC and other carcinomas, as reported in previous studies, such as let-7, miR-21, miR-24, and miR-486. The results indicated that miR-181-5p, miR-30a-3p, miR-30e-3p, and miR-361-5p were adenocarcinoma-specific, and miR-10b-5p, miR-15b-5p, and miR-320b were SCC-specific. The diagnostic accuracy of three combination miRNA panels was evaluated using an AUC value of 0.899, 0.936, and 0.911 for detecting NSCLC, adenocarcinoma, and SCC, respectively.Conclusions: Tumor-derived exosomal miRNAs, adenocarcinoma-specific miR-181-5p, miR-30a-3p, miR-30e-3p and miR-361-5p, and SCC-specific miR-10b-5p, miR-15b-5p, and miR-320b were observed by next-generation sequencing, and their diagnostic accuracy were verified. These miRNAs may be promising and effective candidates in the development of highly sensitive, noninvasive biomarkers for early NSCLC diagnosis. Clin Cancer Res; 23(17); 5311-9. ©2017 AACR.

Dosimetric advantage of volumetric modulated arc therapy in the treatment of intraocular cancer.

OBJECTIVE: The purpose of this study is to investigate the dosimetric advantages of volumetric modulated arc therapy (VMAT) in the treatment of intraocular cancer by comparing it directly with three-dimensional conformal radiotherapy (CRT) and intensity-modulated radiotherapy (IMRT). METHODS: CRT plan, 7f-IMRT plan, and one-arc VMAT plan were generated for 14 intraocular cancer patients. Dosimetric and biological quality indices for target volume and organs at risks (OARs) were evaluated and compared. RESULTS: The target coverage presented by V95 for CRT, IMRT and VMAT were 95.02% ± 0.67%, 95.51% ± 2.25%, and 95.92% ± 3.05%, respectively. The homogeneity index (HI) for CRT, IMRT and VMAT were 0.15 ± 0.05, 0.23 ± 0.05, and 0.23 ± 0.06, respectively. IMRT and VMAT greatly decreased the dose to ipsilateral lens compared with CRT with a D1 of 2972.66 ± 1407.12 cGy, 3317.82 ± 915.28 cGy and 4809.54 ± 524.60 cGy for IMRT, VMAT and CRT, respectively. Similar results were observed for ipsilateral eyeballs. IMRT and VMAT also spared better on brainstem, optical nerves and optical chiasm compared CRT. However, CRT achieved lower dose to the eyeballs compared with IMRT and VMAT. VMAT and IMRT showed mixed results on target coverage and OAR sparing. The average MUs and delivery time of IMRT and VMAT were 531.25 ± 81.21 vs. 400.99 ± 61.49 and 5.05 ± 0.53 vs.1.71 ± 0.69 min, respectively. CONCLUSIONS: Although no clear distinction on PTV coverage among CRT, IMRT and VMAT plans was observed in the treatment of intraocular cancer, VMAT and IMRT achieved better homogeneity and conformity for target volume, and delivered fewer doses to ipsilateral lens and eyeballs compared with CRT. However, VMAT and IMRT increased the low dose volume to the contralateral OARs. Although VMAT and IMRT showed mixed results on target coverage and OAR sparing, VMAT decreased MU and delivery time significantly compared with IMRT. VMAT is a promising and feasible external beam radiotherapy technique in the treatment of intraocular cancer patients.

Profiling and bioinformatics analyses reveal differential circular RNA expression in radioresistant esophageal cancer cells.

BACKGROUND: Acquired radioresistance during radiotherapy is considered as the most important reason for local tumor recurrence or treatment failure. Circular RNAs (circRNAs) have recently been identified as microRNA sponges and involve in various biological processes. The purpose of this study is to investigate the role of circRNAs in the radioresistance of esophageal cancer. METHODS: Total RNA was isolated from human parental cell line KYSE-150 and self-established radioresistant esophageal cancer cell line KYSE-150R, and hybridized to Arraystar Human circRNA Array. Quantitative real-time PCR was used to confirm the circRNA expression profiles obtained from the microarray data. Bioinformatic tools including gene ontology (GO) analysis, KEGG pathway analysis and network analysis were done for further assessment. RESULTS: Among the detected candidate 3752 circRNA genes, significant upregulation of 57 circRNAs and downregulation of 17 circRNAs in human radioresistant esophageal cancer cell line KYSE-150R were observed compared with the parental cell line KYSE-150 (fold change ≥2.0 and P < 0.05). There were 9 out of these candidate circRNAs were validated by real-time PCR. GO analysis revealed that numerous target genes, including most microRNAs were involved in the biological processes. There were more than 400 target genes enrichment on Wnt signaling pathway. CircRNA_001059 and circRNA_000167 were the two largest nodes in circRNA/microRNA co-expression network. CONCLUSIONS: Our study revealed a comprehensive expression and functional profile of differentially expressed circRNAs in radioresistant esophageal cancer cells, indicating possible involvement of these dysregulated circRNAs in the development of radiation resistance.

Inhibition of cyclin D1 enhances sensitivity to radiotherapy and reverses epithelial to mesenchymal transition for esophageal cancer cells.

Acquired radioresistance during radiotherapy has significantly affected the treatment efficacy in esophageal cancer. Many of radioresistant cancer cells demonstrated epithelial-mesenchymal transition (EMT).We found in previous study that a radioresistant cell line (KYSE-150R) possessed EMT characteristic with cyclin D1 overexpression. Cyclin D1 has been demonstrated to affect the radiation sensitivity in cancer cells. To elucidate the molecular functions of cyclin D1 on EMT phenotypes and esophageal cancer radiosensitivity, we treated the radioresistant esophageal cancer cells (KYSE-150R) and parental cells (KYSE-150) with cyclin D1 small interfering RNA (siRNA). The cell proliferation rate of KYSE-150R and the radiation survival fraction were significantly decreased in cyclin D1 siRNA treatment group. Knocking down cyclin D1 resulted in G0/G1 arrest in KYSE-150R cells. The average number of irradiation-induced γ-H2AX foci increased in the cells treated with cyclin D1 siRNA, indicating impaired DNA double-strand break (DSB) repair in KYSE-150R cells. Cyclin D1 also reversed EMT phenotypes with significantly increased expression of E-cadherin in KYSE-150R cells. However, cyclin D1 siRNA have no radiosensitizing effects on KYSE-150 cells, with no obvious change in EMT marker expression .Our work showed that EMT phenotypes can be reduced and the radiosensitivity of esophageal cancer cells can be enhanced by inhibiting cyclin D1.

FH535 increases the radiosensitivity and reverses epithelial-to-mesenchymal transition of radioresistant esophageal cancer cell line KYSE-150R.

BACKGROUND: Acquired radioresistance has significantly compromised the efficacy of radiotherapy for esophageal cancer. The purpose of this study is to investigate the roles of epithelial-mesenchymal transition (EMT) and the Wnt/ß-catenin signaling pathway in the acquirement of radioresistance during the radiation treatment of esophageal cancer. METHODS: We previously established a radioresistant cell line (KYSE-150R) from the KYSE-150 cell line (a human cell line model for esophageal squamous cell carcinoma) with a gradient cumulative irradiation dose. In this study, the expression of EMT phenotypes and the Wnt/ß-catenin signaling pathway proteins were examined by real-time PCR, western blot and immunofluorescence in the KYSE-150R cells. The KYSE-150R cells were then treated with a ß-Catenin/Tcf inhibitor FH535. The expressions of nuclear and cytoplasmic ß-catenin and EMT markers in KYSE-150R cells were assessed at both mRNA and protein level after FH535 treatment. The radiosensitization effect of FH535 on KYSE-150R was evaluated by CCK8 analysis and a colony forming assay. DNA repair capacities was detected by the neutral comet assays. RESULTS: KYSE-150R cell line displayed obvious radiation resistance and had a stable genetic ability. EMT phenotype was presented in the KYSE-150R cells with decreased E-cadherin and increased snail and twist expressions. The up-regulated expressions of Wnt/ß-catenin signaling pathway proteins (Wnt1, FZD1-4, GSK3ß, CTNNB1 and Cyclin D1), the increased phosphorylation of GSK3ß, and the decreased phosphorylation of ß-catenin were observed in KYSE-150R cells compared with KYSE-150 cells, implicating the activation of the Wnt pathway in KYSE-150R cells. The expression of nuclear ß-catenin and nuclear translocation of ß-catenin from the cytoplasm was decreased after FH535 treatment. FH535 also reversed EMT phenotypes by increasing E-cadherin expression. The cell proliferation rates of KYSE-150R were dose-dependent and the radiation survival fraction was significantly decreased upon FH535 treatment. Neutral comet assays indicated that FH535 impairs DNA double stranded break repair in KYSE-150R cells. CONCLUSIONS: Acquisition of radioresistance and EMT in esophageal cancer cells is associated with the activation of the Wnt/ß-catenin pathway. EMT phenotypes can be reduced and the radiosensitivity of esophageal cancer cells can be enhanced by inhibiting the Wnt/ß-catenin pathway with FH535 treatment.

Down-regulation of Dicer expression in cervical cancer tissues.

Dicer is a component of the MicroRNA-producing machinery. The altered expression of Dicer may play a role in oncogenesis. The purpose of this study was to evaluate the expression of Dicer in cervical cancer tissues and its significance. Cancer tissues, para-cancer tissues and corresponding normal tissues were obtained from 31 cervical cancer patients undergoing surgery. Expression levels of Dicer mRNA were evaluated in these tissues using the real-time reverse transcription PCR. The association of the Dicer expression levels with clinical characteristics was also examined. The expression levels of Dicer mRNA were decreased in 66.7% (18/27) and 76.9% (20/26) of cervical cancer and para-cancer specimens, respectively, compared with corresponding normal tissues. The lower expression levels of Dicer in cancer tissues were associated with advanced tumor stages (p = 0.03) and with metastasis (p = 0.01). The down-regulation of Dicer expression in cancer and para-cancer tissues was observed. The lower expression of Dicer in cancer tissues demonstrated to be associated with tumor stages and metastasis. Future studies with a greater number of tissues to more conclusively determine the extent of low-level expression of Dicer in cervical cancer are warranted.

Identification of microRNAs involved in the radioresistance of esophageal cancer cells.

Radioresistance is considered as the most important reason for local tumour recurrence. This study investigates the role of miRNAs in radioresistant human esophageal cancer cells. Human miRNA microarray has been used to detect the differential expressed microRNAs between radioresistant esophageal cell line KYSE-150R and the parental cell line KYSE-150. The relative expression of some candidate miRNAs was measured by quantitative real-time PCR (qRT-PCR). Potential mRNA targets were analysed bioinformatically. Significant upregulation of 10 microRNAs and downregulation of 25 microRNAs were detected. The statistical significance of downregulation in hsa-miR-301a, hsa-miR-141 and hsa-miR-18b expression (P < 0.05) were confirmed by qRT-PCR. The correlation of the predicted microRNA target genes to apoptosis (63 genes), cell cycle (67 genes), DNA damage and repair (18 genes) were confirmed by functional annotation. The downregulation of hsa-miR-301a promoted radioresistance in KYSE-150R through the upregulation of wnt1, indicating that wnt/ß-catenin signal pathway might be important in radioresistance. In conclusion, a unique set of miRNAs and their expression profiles in radiation resistance have been identified, providing a solid basis for future studies to investigate the target genes of these miRNAs and their function.