Background: Circular RNA (circRNA) and N6‐methyladenosine (m6A) play a critical role in tumour occurrence and development, including colorectal cancer (CRC). However, little is known about the interaction between circRNA and m6A in the radiosensitivity of CRC. Here, we investigated the role of a novel m6A‐regulated circRNA in CRC.Methods: Differentially expressed circRNAs from radiosensitive and radioresistant CRC tissues were screened. Modifications of the selected circRNAs were examined by methylated RNA immunoprecipitation assay. Finally, the selected circRNAs were subjected to radiosensitivity assay.Results: We identified that circAFF2 is closely related to both radiosensitivity and m6A in CRC. CircAFF2 was highly expressed in patients with radiosensitive rectal cancer, and patients with high expression of circAFF2 had a better prognosis. In addition, circAFF2 can enhance the radiosensitivity of CRC cells both in vitro and in vivo. The regulation of circAFF2 involves ALKBH5‐mediated demethylation, followed by its recognition and degradation via YTHDF2. Rescue experiments revealed that circAFF2 could reverse the radiosensitivity induced by ALKBH5 or YTHDF2. Mechanistically, circAFF2 binds with CAND1, promotes the binding of CAND1 to Cullin1 and inhibits its neddylation, subsequently impacting the radiosensitivity of CRC.Conclusion: We identified and characterised circAFF2 as a novel m6A‐modified circRNA and validated the ALKBH5/YTHDF2/circAFF2/Cullin‐NEDD8 axis as a potential radiotherapy target for CRC.

The Systemic Inflammation Response Index (SIRI), based on peripheral lymphocyte, neutrophil, and monocyte counts, was recently investigated as a prognostic marker for several tumors. However, use of the SIRI has not been reported for nasopharyngeal carcinoma (NPC). We evaluated the prognostic value of the SIRI in primary and validation cohorts. We also established an effective prognostic nomogram for NPC based on clinicopathological parameters and the SIRI. The predictive accuracy and discriminative ability of the nomogram were determined using the concordance index (C-index) and a calibration curve and were compared with tumor-node-metastasis classifications. Our Kaplan-Meier survival analysis results showed that the SIRI was associated with the overall survival of patients with NPC in the primary and validation cohorts. The SIRI was identified to be an independent prognostic factor for NPC. In addition, we developed and validated a new prognostic nomogram that integrated clinicopathological factors and the SIRI. This nomogram can efficiently predict the prognosis of patients with NPC. The SIRI is a novel, simple and inexpensive prognostic predictor for patients with NPC. The SIRI has important value for predicting the prognosis of patients with NPC and developing individualized treatment plans.

Radiotherapy is one of the most important treatment methods of tumors. However, the application of radiotherapy in hepatocellular carcinoma (HCC) is limited due to the low tolerance of normal liver cells for radiation and inherent radiation resistance in HCC. With the in-depth study of microRNAs (miRNAs) in tumor therapy, the regulation of tumor radiosensitivity by miRNAs has been a research hotspot in recent years. In the present study, the expression of miR-621 was lower in HCC tissues and cells, and such low expression of miR-621 was associated with poor prognosis in HCC patients. In addition, in vivo and in vitro assays confirmed that the high expression of miR-621 could significantly enhance the radiosensitivity of HCC. Moreover, the expressions of miR-621 and SETDB1 in HCC tissues were negatively correlated. Dual-luciferase reporter assays indicated that miR-621 could directly target the 3' UTR of SETDB1. In addition, miR-621 enhanced the radiosensitivity of HCC cells via directly inhibiting SETDB1. Besides, the miR-621 and/or SETDB1 axis improved the radiosensitivity of HCC cells via activating the p53-signaling pathway. Taken together, miR-621 and/or SETDB1 might be used as a novel therapeutic target for the treatment of HCC.

Background: Patients with regional lymph node recurrence after radical resection of esophageal cancer have poor therapeutic outcomes. Currently, there is no standard treatment for regional lymph node recurrence, and its prognostic risk factors are not well-understood. This study retrospectively analyzed 83 patients with postoperative regional lymph node recurrence after radical resection of esophageal squamous cell carcinoma. The aim was to evaluate the clinical efficacy and prognostic factors of salvage radiotherapy with or without chemotherapy in these patients.Methods: The survival and prognostic factors of 83 patients with esophageal squamous cell carcinoma with regional lymph node recurrence after radical surgery were retrospectively analyzed. All patients underwent radiotherapy, of which 74 patients received volumetric modulated arc therapy (VMAT), 9 patients received three-dimensional conformal radiation therapy (3DCRT), administered using a conventional segmentation protocol with a dose distribution range of 50.4–66.2Gy (median dose of 60Gy). In total, 41 patients received radiotherapy alone, 42 received radiotherapy combined with chemotherapy, and the concurrent chemotherapy regimen was mainly composed of either platinum or fluorouracil monotherapy, except for 4 patients who were given 5-fluorouracil plus platinum (FP) or paclitaxel plus platinum (TP).Results: The median follow-up time was 24 (range, 9–75) months. The overall survival (OS) rates at 1 year, 2 years, 3 years, and 5 years were 83.0, 57.1, 40.1, and 35.1%, respectively. The median overall survival (OS) time was 18 (range, 5–75) months. The 3-year survival rate was 47.5% in patients with radiation alone and 41.9% in patients receiving concurrent chemoradiotherapy(p = 0.570), while the response rate (CR + PR) in those two groups was 73.2 and 91.4%, respectively. By multivariate analysis of OS, age (worse in younger patients,p = 0.034) was found to be significantly associated with disease prognosis. The commonly toxicities were esophagitis, neutropenia and anemia. 18% patients experienced grade 3 toxicity and no treatment-related death occurred.Conclusions: These results of this retrospective analysis suggest that radiotherapy with or without chemotherapy is an effective and feasible salvage treatment for lymph node recurrence after radical resection of esophageal squamous cell carcinoma.

RNA modification, like DNA methylation, histone modification, non-coding RNA modification and chromatin rearrangement, plays an important role in tumours. N6-methyladenosine (m6A) is the most abundant RNA modification in cells, and it regulates RNA transcription, processing, splicing, degradation, and translation. m6A-associated proteins have been used as new biomarkers and therapeutic targets for tumour prediction and monitoring. There are three main types of proteins involved in m6A methylation: methyltransferases (METTL3, METTL14, WTAP, RBM15, ZC3H13 and KIAA1429), demethylases (FTO, ALKBH5 and ALKBH3) and RNA-binding proteins (YTHDF1-3, YTHDC1-2, IGF2BPs and HNRNPs). This article reviews the origins, characteristics and functions of m6A and its relationship with digestive system tumours based on recent research. The expression of m6A regulators can be used as an evaluation indicator of tumour growth and progression and as a prognostic indicator. In-depth research on m6A methylation in digestive system tumours may provide new directions for clinical prediction and further treatment.

This study aimed to investigate the difference in pain relief between stereotactic body radiation therapy (SBRT) and conventional radiation therapy (cRT) for patients with bone metastases. Clinical trials and observational studies comparing SBRT versus cRT for bone metastases were retrieved. The main endpoint was pain relief after radiation therapy; the secondary endpoints were pain score change, local progression-free survival, reirradiation rate, and toxic events. When there was a significant heterogeneity, the random-effects model was applied. Otherwise, the fixed-effects model was used. Analyses of all included studies were performed first, followed by analyses of randomized controlled trials (RCTs) only. Six RCTs, 1 prospective cohort study, and 3 retrospective observational studies were enrolled. Between 2004 and 2019, 448 patients received SBRT, and 445 patients received cRT. All prospective studies defined the lesions as oligometastatic. Pooled results based on all included studies indicated that SBRT was generally associated with a higher overall relief rate (P < .001 at 3 months; P = .015 at 6 months) and complete relief rate (P = .029 at 1 month; P < .001 at 6 months). Pooled results based on RCTs indicated that at 3 and 6 months, SBRT was associated with a higher overall relief rate (P < .001 and P = .017, respectively) and complete relief rate (P < .001 and P < .00, respectively). Subgroup analyses indicated that in more cases, the analgesic advantage of SBRT was more obvious when spinal lesions were irradiated, when the difference in the mean biological effective dose (BED) was less, or when intensity modulated radiation therapy was used to deliver SBRT. Excessive elevation of BED introduces the risk of diminishing the analgesic effect of SBRT. SBRT delivered using intensity modulated radiation therapy is preferred for pain relief in spinal oligometastases. More RCTs are required to determine the most appropriate BED or dose regimen for SBRT.