Radiation-induced upregulation of FGL1 promotes esophageal squamous cell carcinoma metastasis via IMPDH1.

BACKGROUND: While radiation therapy remains pivotal in esophageal squamous cell carcinoma (ESCC) treatment, the perplexing phenomenon of post-radiation metastasis presents a formidable clinical challenge. This study investigates the role of fibrinogen-like protein 1 (FGL1) in driving ESCC metastasis following radiation exposure. METHODS: FGL1 expression in post-radiation ESCC cells was meticulously examined using qRT-PCR, western blotting, and immunofluorescence. The impact of FGL1 on ESCC cell invasion and migration was assessed through Transwell and wound healing assays. In vivo, the metastatic potential of ESCC in response to FGL1 was scrutinized using nude mice models. Comprehensive RNA sequencing and functional experiments elucidated the intricate mechanism associated with FGL1. RESULTS: Radiation induced upregulation of FGL1 in ESCC cells through FOXO4, intensifying ESCC cell invasion and migration. Targeted knockdown of FGL1 effectively alleviated these characteristics both in vitro and in vivo. FGL1 depletion concurrently suppressed IMPDH1 expression. Rescue experiments underscored that IMPDH1 knockdown robustly reversed the pro-invasive effects induced by FGL1 in ESCC cells. ESCC tissues exhibited heightened IMPDH1 mRNA levels, demonstrating a correlation with patient survival. CONCLUSIONS: Radiation-induced upregulation of FGL1 propels ESCC metastasis through IMPDH1, proposing a potential therapeutic target to mitigate post-radiotherapy metastasis in ESCC patients.

Exploration of lymph node recurrence patterns and delineation guidelines of radiation field in middle thoracic oesophageal carcinomas after radical surgery: a real-world study.

BACKGROUND: Oesophageal squamous cell carcinoma is one of the most commonly diagnosed carcinomas in China, and postoperative radiotherapy plays an important role in improving the prognosis of patients. Carcinomas in different locations of the oesophagus could have different patterns of lymph node metastasis after surgery. METHODS: In this multicentric retrospective study, we enrolled patients with middle thoracic oesophageal squamous cell carcinomas from 3 cancer centres, and none of the patients underwent radiotherapy before or after surgery. We analysed the lymph node recurrence rates in different stations to explore the postoperative lymphatic recurrence pattern. RESULTS: From January 1st, 2014, to December 31st, 2019, 132 patients met the criteria, and were included in this study. The lymphatic recurrence rate was 62.1%. Pathological stage (P = 0.032) and lymphadenectomy method (P = 0.006) were significant predictive factors of lymph node recurrence. The recurrence rates in the supraclavicular, upper and lower paratracheal stations of lymph nodes were 32.6%, 28.8% and 16.7%, respectively, showing a high incidence. The recurrence rate of the subcarinal node station was 9.8%, while 8.3% (upper, middle and lower) thoracic para-oesophageal nodes had recurrences. CONCLUSIONS: We recommend including the supraclavicular, upper and lower paratracheal stations of lymph nodes in the postoperative radiation field in middle thoracic oesophageal carcinomas. Subcarinal station is also potentially high-risk, while whether to include thoracic para-oesophageal or abdominal nodes needs careful consideration.

HRU-Net: A high-resolution convolutional neural network for esophageal cancer radiotherapy target segmentation.

BACKGROUND AND OBJECTIVE: The effective segmentation of esophageal squamous carcinoma lesions in CT scans is significant for auxiliary diagnosis and treatment. However, accurate lesion segmentation is still a challenging task due to the irregular form of the esophagus and small size, the inconsistency of spatio-temporal structure, and low contrast of esophagus and its peripheral tissues in medical images. The objective of this study is to improve the segmentation effect of esophageal squamous cell carcinoma lesions. METHODS: It is critical for a segmentation network to effectively extract 3D discriminative features to distinguish esophageal cancers from some visually closed adjacent esophageal tissues and organs. In this work, an efficient HRU-Net architecture (High-Resolution U-Net) was exploited for esophageal cancer and esophageal carcinoma segmentation in CT slices. Based on the idea of localization first and segmentation later, the HRU-Net locates the esophageal region before segmentation. In addition, an Resolution Fusion Module (RFM) was designed to integrate the information of adjacent resolution feature maps to obtain strong semantic information, as well as preserve the high-resolution features. RESULTS: Compared with the other five typical methods, the devised HRU-Net is capable of generating superior segmentation results. CONCLUSIONS: Our proposed HRU-NET improves the accuracy of segmentation for squamous esophageal cancer. Compared to other models, our model performs the best. The designed method may improve the efficiency of clinical diagnosis of esophageal squamous cell carcinoma lesions.

Radiotherapy for patients with esophageal cancer aged 80 years or older: A 16-year experience.

PURPOSE: Radiotherapy (RT) plays an important role in esophageal cancer (EC) patients aged ≥80 years. However, the survival modality and prognostic factors remain poorly understood. Thus, this study aimed to evaluate the tolerance and long-term overall survival (OS) of patients aged ≥80 years who were diagnosed with EC and underwent definitive RT. MATERIALS AND METHODS: A total of 213 consecutive patients with EC over 80 years old who were treated with curative intent RT between February 1999 and December 2015 at our institution were retrospectively reviewed. The clinical prognostic variables were analyzed against OS in univariate analyses using log-rank tests and in a multivariate model using Cox regression proportional hazards analysis. RESULT: The median patient age was 82 (range: 80-94) years. Atotal of 192 patients (90.1%) completed the definitive RT (median: 60 Gy, range: 50-72 Gy), and 11 patients had grade 4 or higher acute toxicity, including esophagitis, a cardiac event, infections, and sudden death. Atotal of 168 deaths (78.9%) were observed with a median follow up of 47 months (range: 0-153 months). The OS rates were 50.3%, 17.6%, and 13.2% at 1, 3, and 5 years, respectively. Multivariable analysis identified that tumors located in the cervical and upper thorax, a shorter tumor lesion, RT treatment of 50-60Gy, and a better response to treatment were the factors associated with longer OS. CONCLUSION: Definitive RT could be considered as an effective treatment for patients with EC who are older than 80 years, and 50-60 Gy seems to be a reasonable dose for these patients.

Impact of FAPI-46/dual-tracer PET/CT imaging on radiotherapeutic management in esophageal cancer.

BACKGROUND: Fibroblast activation protein (FAP) is expressed in the tumor microenvironment (TME) of various cancers. In our analysis, we describe the impact of dual-tracer imaging with Gallium-68-radiolabeled inhibitors of FAP (FAPI-46-PET/CT) and fluorodeoxy-D-glucose (FDG-PET/CT) on the radiotherapeutic management of primary esophageal cancer (EC). METHODS: 32 patients with EC, who are scheduled for chemoradiation, received FDG and FAPI-46 PET/CT on the same day (dual-tracer protocol, 71%) or on two separate days (29%) We compared functional tumor volumes (FTVs), gross tumor volumes (GTVs) and tumor stages before and after PET-imaging. Changes in treatment were categorized as "minor" (adaption of radiation field) or "major" (change of treatment regimen). Immunohistochemistry (IHC) staining for FAP was performed in all patients with available tissue. RESULTS: Primary tumor was detected in all FAPI-46/dual-tracer scans and in 30/32 (93%) of FDG scans. Compared to the initial staging CT scan, 12/32 patients (38%) were upstaged in nodal status after the combination of FDG and FAPI-46 PET scans. Two lymph node metastases were only visible in FAPI-46/dual-tracer. New distant metastasis was observed in 2/32 (6%) patients following FAPI-4 -PET/CT. Our findings led to larger RT fields ("minor change") in 5/32 patients (16%) and changed treatment regimen ("major change") in 3/32 patients after FAPI-46/dual-tracer PET/CT. GTVs were larger in FAPI-46/dual-tracer scans compared to FDG-PET/CT (mean 99.0 vs. 80.3 ml, respectively (p < 0.001)) with similar results for nuclear medical FTVs. IHC revealed heterogenous FAP-expression in all specimens (mean H-score: 36.3 (SD 24.6)) without correlation between FAP expression in IHC and FAPI tracer uptake in PET/CT. CONCLUSION: We report first data on the use of PET with FAPI-46 for patients with EC, who are scheduled to receive RT. Tumor uptake was high and not depending on FAP expression in TME. Further, FAPI-46/dual-tracer PET had relevant impact on management in this setting. Our data calls for prospective evaluation of FAPI-46/dual-tracer PET to improve clinical outcomes of EC.

Inflammatory and Nutritional Biomarkers in Patients With Esophageal Squamous Cell Carcinoma Undergoing Neoadjuvant Chemotherapy and Radiation Therapy.

OBJECTIVES: To investigate the relationship between pretreatment inflammatory and nutritional biomarkers in patients with esophageal squamous cell carcinoma (ESCC) undergoing neoadjuvant chemotherapy and radiation therapy (nCRT). SAMPLE & SETTING: 213 patients with newly diagnosed stage II-III ESCC who received nCRT at an academic hospital in Taiwan. METHODS & VARIABLES: Electronic health record data were used. Records on inflammatory and nutritional biomarkers and clinical outcomes were extracted. Logistic regression analysis was used to predict treatment-related adverse events, Cox regression was used for survival outcomes, and receiver operating characteristic curve analysis was used to determine optimal cutoff values. RESULTS: There was a significant association between low prognostic nutritional index (PNI) and nCRT toxicities and survival. Advanced cancer stage, high platelet-to-lymphocyte ratio, and occurrence of pneumonia/infection were linked to survival outcomes. IMPLICATIONS FOR NURSING: PNI shows promise in predicting prognosis, helps identify high-risk patients, and enables nurses to apply tailored interventions.

A nomogram based on clinical characteristics and nutritional indicators for relative and absolute weight loss during radiotherapy in initially inoperable patients with locally advanced esophageal squamous cell carcinoma.

OBJECTIVE: Radiation for locally advanced esophageal squamous cell carcinoma often is accompanied by radiation esophagitis, which interferes with oral intake. We aimed to develop a nomogram model to identify initially inoperable patients with relative and absolute weight loss who need prophylactic nutritional supplementation. METHODS: A total of 365 initially inoperable patients with locally advanced esophageal squamous cell carcinoma receiving radiotherapy between January 2018 and December 2022 were included in the study, which was divided into discovery and validation cohorts. Receiver operating characteristic and Kaplan-Meier curve analyses were performed to compare the areas under the curve and survival benefits. RESULTS: A total of 42.2% (154 of 365) of the patients had been diagnosed with cancer cachexia. The malnourished group had a higher interruption rate of radiotherapy and number of complication diseases (P < 0.05). Meanwhile, patients with malnutrition had lower lymphocytes and prognostic nutritional index (P < 0.05). The combined index showed a higher area under the curve value (0.67; P < 0.001) than number of complication diseases (area under the curve = 0.52) and prognostic nutritional index (area under the curve = 0.49) for relative weight loss (≥ 5%). Similarly, the combined index had a higher area under the curve value (0.79; P < 0.001) than number of complication diseases (area under the curve = 0.56), treatment regimens (area under the curve = 0.56), subcutaneous fat thickness (area under the curve = 0.60), pretreatment body weight (area under the curve = 0.61), neutrophils (area under the curve = 0.56), and prognostic nutritional index (area under the curve = 0.50) for absolute weight loss (≥ 5 kg). Absolute and relative weight loss remained independent prognostic factors, with short overall survival rates compared with the normal group (P < 0.05). Patients with high nomogram scores supported by nutritional intervention had less weight loss, better nutrition scores, and increased plasma CD8+ T cells, and interferon gamma. CONCLUSIONS: We developed a nomogram model that was intended to estimate relative and absolute weight loss in initially inoperable patients with locally advanced esophageal squamous cell carcinoma during radiotherapy, which might help facilitate an objective decision on prophylactic nutritional supplementation.

Correlation between morphological parameters and dosimetric parameters of the heart and spinal cord in the intermediate- and advanced-stage esophageal cancer.

BACKGROUND: Radiation therapy plays a pivotal role as the primary adjuvant treatment for esophageal cancer (EPC), emphasizing the critical importance of carefully balancing radiation doses to the target area and organs at risk in the radiotherapeutic management of esophageal cancer. AIMS: This study aimed to explore the correlation between morphological parameters and dosimetric parameters of the heart and spinal cord in intermediate- and advanced-stage esophagus cancer to provide a reference for clinical treatment. METHODS AND RESULTS: A total of 105 patients with intermediate- and advanced-stage EPC, who received treatment in our hospital from 2019 to 2021, were included. The morphological parameters were calculated by imaging. Intensity-modulated radiation therapy plan was executed at Raystation4.7. The PTV-G stood for the externally expanded planning target volume (PTV) of the gross tumor volume (GTV) and PTV-C for the externally expanded volume of the clinical target volume (CTV). The prescription dose of PTV-G and PTV-C was set as 60Gy/30F and 54Gy/30F, respectively. The linear regression model was used to analyze the correlation between morphologic parameters of EPC and dosimetric parameters of the heart and spinal cord. In 105 cases, the total lung length was correlated with the spinal cord maximum dose (D2 ). The heart mean doses (Dmean ) and heart V40 (the relative volume that receives 40 Gy or more) was correlated with PTV-G volume, PTV-G length; In middle- and upper-segment EPC cases, only the total lung volume was correlated with the spinal cord Dmean , spinal cord D2 , heart Dmean , and heart V40 ; In middle-stage EPC cases, the heart Dmean was correlated with the PTV-G volume, PTV-G length. The total lung length was correlated with the spinal cord D2 ; In middle- and lower-segment EPC, only the PTV-G volume and PTV-G length were correlated with the heart Dmean . All the aforementioned values were statistically significant. CONCLUSIONS: Combined with the unsegmented tumor and different locations, the organ at risk dose was comprehensively considered.

Efficacy of the collapsed cone algorithm calculated radiotherapy plans in intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT): A comparative dosimetric study in tumors of thorax.

AIM: In this study, efficacy of collapsed cone algorithm-generated intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) were evaluated for treatment of thoracic esophageal cancer. MATERIALS AND METHODS: Ten previously treated patients with VMAT were considered for evaluation. The planning parameters were evaluated in terms of max dose, mean dose, Homogeneity Index, Conformity Index for planning target volume, and organ at risk doses. Total monitor unit, treatment time, and gamma passing index were also reported. RESULTS: The target dose coverage of the VMAT and IMRT plans achieved the clinical dosimetric criteria for all ten patients in the evaluation. Under the condition of equivalent target dose distribution, the VMAT plan's Conformity Index, monitor unit, treatment time, and gamma passing index rate were superior than in the IMRT plan, and the result was statistically significant. CONCLUSION: Collapsed cone algorithm-based VMAT can have a more effective and better approach for esophageal cancer than IMRT.

Consolidation chemotherapy after definitive concurrent chemoradiotherapy in patients with inoperable esophageal squamous cell carcinoma: a multicenter non-inferiority phase III randomized clinical trial.

BACKGROUND: Definitive concurrent chemoradiotherapy (dCCRT) is the gold standard for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC). However, the potential benefits of consolidation chemotherapy after dCCRT in patients with esophageal cancer remain debatable. Prospective randomized controlled trials comparing the outcomes of dCCRT with or without consolidation chemotherapy in patients with ESCC are lacking. In this study, we aim to generate evidence regarding consolidation chemotherapy efficacy in patients with locally advanced, inoperable ESCC. METHODS: This is a multicenter, prospective, open-label, phase-III randomized controlled trial comparing non-inferiority of dCCRT alone to consolidation chemotherapy following dCCRT. In total, 600 patients will be enrolled and randomly assigned in a 1:1 ratio to receive either consolidation chemotherapy after dCCRT (Arm A) or dCCRT alone (Arm B). Overall survival will be the primary endpoint, whereas progression-free survival, locoregional progression-free survival, distant metastasis-free survival, and treatment-related toxicity will be the secondary endpoints. DISCUSSION: This study aid in further understanding the effects of consolidation chemotherapy after dCCRT in patients with locally advanced, inoperable ESCC. TRIAL REGISTRATION: ChiCTR1800017646.

The role of spleen radiomics model for predicting prognosis in esophageal squamous cell carcinoma patients receiving definitive radiotherapy.

BACKGROUND: The spleen plays an important role in systemic antitumor immune response, but whether spleen imaging features have predictive effect for prognosis and immune status was unknown. The aim of this study was to investigate computed tomography (CT)-based spleen radiomics to predict the prognosis of patients with esophageal squamous cell carcinoma (ESCC) underwent definitive radiotherapy (dRT) and to try to find its association with systemic immunity. METHODS: This retrospective study included 201 ESCC patients who received dRT. Patients were randomly divided into training (n = 142) and validation (n = 59) groups. The pre- and delta-radiomic features were extracted from enhanced CT images. LASSO-Cox regression was used to select the radiomics signatures most associated with progression-free survival (PFS) and overall survival (OS). Independent prognostic factors were identified by univariate and multivariate Cox analyses. The ROC curve and C-index were used to evaluate the predictive performance. Finally, the correlation between spleen radiomics and immune-related hematological parameters was analyzed by spearman correlation analysis. RESULTS: Independent prognostic factors involved TNM stage, treatment regimen, tumor location, pre- or delta-Rad-score. The AUC of the delta-radiomics combined model was better than other models in the training and validation groups in predicting PFS (0.829 and 0.875, respectively) and OS (0.857 and 0.835, respectively). Furthermore, some spleen delta-radiomic features are significantly correlated with delta-ALC (absolute lymphocyte count) and delta-NLR (neutrophil-to-lymphocyte ratio). CONCLUSIONS: Spleen radiomics is expected to be a useful noninvasive tool for predicting the prognosis and evaluating systemic immune status for ESCC patients underwent dRT.

Circ-POSTN promotes the progression and reduces radiosensitivity in esophageal cancer by regulating the miR-876-5p/FYN axis.

BACKGROUND: Circular RNAs (circRNAs) play critical roles in the tumorigenesis and radiosensitivity of multiple cancers. Nevertheless, the biological functions of circRNA periostin (circ-POSTN) in esophageal cancer (EC) progression and radiosensitivity have not been well elucidated. METHODS: The expression of circ-POSTN, microRNA-876-5p (miR-876-5p), and proto-oncogene tyrosine-protein kinase (FYN) was analyzed by quantitative reverse transcription PCR (RT-qPCR). Cell proliferation was assessed by MTT, colony formation, and 5-ethynyl-2'-deoxyuridine (EDU) assays. All protein levels were detected by western blot assay. Cell apoptosis and invasion were assessed by flow cytometry analysis and transwell assay, respectively. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to validate the interaction between miR-876-5p and circ-POSTN or FYN. The role of circ-POSTN in vivo was explored by establishing mice xenograft model. RESULTS: Circ-POSTN was overexpressed in EC tissues and cells. Knockdown of circ-POSTN inhibited cell proliferation and invasion and elevated apoptosis and radiosensitivity in EC cells. MiR-876-5p was a direct target of circ-POSTN, and its knockdown reversed the role of sh-circ-POSTN in EC cells. FYN was a direct target of miR-876-5p, and FYN elevation weakened the effects of miR-876-5p overexpression on the progression and radiosensitivity of EC cells. Moreover, circ-POSTN acted as a miR-876-5p sponge to regulate FYN expression. Circ-POSTN interference also suppressed tumor growth and enhanced radiosensitivity in vivo. CONCLUSION: Circ-POSTN knockdown inhibited proliferation and invasion, but increased apoptosis and enhanced radiosensitivity in EC cells via modulating miR-876-5p/FYN axis, which might be a potential diagnostic and therapeutic target for EC.

Esophagogastric Cancer: The Current Role of Radiation Therapy.

Radiation therapy is an effective treatment modality in the management of patients with esophageal cancer regardless of tumor location (proximal, middle, or distal esophagus) or histology (squamous cell vs adenocarcinoma). The addition of neoadjuvant CRT to surgery in patients who are surgical candidates has consistently shown a benefit in terms of locoregional recurrence, pathologic downstaging, and overall survival. For patients who are not surgical candidates, CRT has a role as definitive treatment.

Effects of intensity-modulated radiotherapy combined with chemotherapy and prognostic factors in patients with locally advanced oesophageal cancer.

PURPOSE: We explored the efficacy and influencing factors of chemoradiotherapy and radiotherapy alone in patients with locally advanced oesophageal squamous cell carcinoma. METHODS: We retrospectively analysed 226 locally advanced oesophageal squamous cell carcinoma patients who underwent chemoradiotherapy and radiotherapy alone. Univariate and multivariate Cox regression analyses were used to analyse the impact of relevant factors. The endpoint was overall survival and progression-free survival. RESULTS: Compared with the radiotherapy group, the chemoradiotherapy group had a significant difference in the overall survival rate and the progression-free survival rate between 3 and 5 years (both p â€‹< â€‹0.05). The incidences of radiation pneumonitis and radiation oesophagitis were analysed, and the differences were not significant (all p â€‹> â€‹0.05). The incidence of haematological toxicity in the chemoradiotherapy group was significantly higher than that in the radiotherapy group (p â€‹= â€‹0.001). There was a significant difference in the incidence of haematological toxicity between the ≤65 and the >65 age groups (p â€‹< â€‹0.05). Tumour location, T stage, tumour length, tumour target volume, and short-term curative effect were the main factors affecting the prognosis (all p â€‹< â€‹0.05). T stage, gross tumour volume, and short-term curative effect were all independent factors affecting the prognosis (all p â€‹< â€‹0.05). CONCLUSIONS: Patients with locally advanced oesophageal cancer who received intensity-modulated radiotherapy (IMRT) combined with chemotherapy had significant survival benefits compared with radiotherapy alone. Haematological toxicity was the main adverse reaction. T-stage, gross tumour volume and short-term curative effect were independent factors influencing the prognosis.

A systematic review of circulating predictive and prognostic biomarkers to aid the personalised use of radiotherapy in the radical treatment of patients with oesophageal cancer.

BACKGROUND: The availability of circulating biomarkers that are predictive of treatment response or prognostic of overall outcome could enable the personalised and adaptive use of radiotherapy (RT) in patients with oesophageal adenocarcinoma (OAC) and squamous cell carcinoma (OSCC). METHODS: A systematic review was carried out following Preferred Reporting Items for Systematic Reviews guidance. Medline, EMBASE, PubMed, Cochrane Library, CINAHL, Scopus and the Web of Science databases were searched for studies published between January 2005-February 2023 relating to circulating biomarkers evaluated in the context of neoadjuvant or definitive RT delivered for OAC/OSCC. Study quality was assessed using predefined criteria. RESULTS: A total of 3012 studies were screened and 57 subsequently included, across which 61 biomarkers were reported. A majority (43/57,75.4%) of studies were of Asian origin and retrospective (40/57, 70.2%), with most (52/57, 91.2%) biomarkers reported in the context of patients with OSCC. There was marked inter-study heterogeneity in patient populations, treatment characteristics, biomarker measurement and the cut points used to define biomarker positivity. Nevertheless, there is evidence for the prognostic and predictive value of circulating tumour DNA and numerous miRNAs in OAC and OSCC, as well as for the prognostic and predictive value of circulating levels of CYFRA21.1 in OSCC. CONCLUSIONS: There is consistent evidence for the potential predictive and prognostic value of a small number of biomarkers in OSCC and OAC, though these data are insufficient for translation to current clinical practice. Well-designed prospective studies are now required to validate their role in stratified and personalised RT treatment approaches.

Exosome-transported of circ_0081069 induces SPIN1 production by binding to miR-195-5p to inhibit radiosensitivity in esophageal squamous cell carcinoma.

Circ_0081069 plays a key role in tumor growth; however, its effect on radiosensitivity in esophageal squamous cell carcinoma (ESCC) remains unknown. The study is performed to reveal the association of circ_0081069 expression and radiosensitivity in ESCC and the underlying mechanism. Circ_0081069, miR-195-5p, and spindlin 1 (SPIN1) RNA expression were detected by quantitative real-time polymerase chain reaction. Protein expression was checked by Western blot analysis or immunohistochemistry assay. Cell viability, proliferation, cell apoptosis, migration, and invasion were investigated by cell counting kit-8, 5-Ethynyl-29-deoxyuridine, flow cytometry analysis, scratch test, and transwell assays, respectively. The sensitivity of ESCC cells to radiation was investigated by cell colony formation assay. The interactions among circ_0081069, miR-195-5p, and SPIN1 were identified by dual-luciferase reporter assay and RNA Immunoprecipitation assay. Xenograft mouse model assay was performed to determine the effect of circ_0007841 on radiosensitivity in vivo. Circ_0081069 and SPIN1 expression were upregulated, whereas miR-195-5p was downregulated in ESCC tissues, ESCC cells, and radiation-stimulated ESCC cells. Circ_0081069 silencing inhibited ESCC cell proliferation, invasion, and migration but improved cell apoptosis. In addition, circ_0081069 knockdown enhanced ESCC cell radiosensitivity in vitro and in vivo. Circ_0081069 bound to miR-195-5p and regulated radiosensitivity by binding to miR-195-5p in ESCC cells. Moreover, SPIN1, a target of miR-195-5p, rescued miR-195-5p-mediated effects in ESCC cells. Circ_0081069 was secreted from ESCC cells by being packaged into exosomes. Further, circ_0081069-Exo inhibited radiosensitivity in ESCC cells. Exosome-mediated transfer of circ_0081069 induced SPIN1 production by binding to miR-195-5p, further inhibiting radiosensitivity in ESCC.

A retrospective cohort study to observe the efficacy and safety of Endoscopic Submucosal Dissection (ESD) with adjuvant radiotherapy for T1a-MM/T1b-SM Esophageal Squamous Cell Carcinoma (ESCC).

BACKGROUND AND AIM: The clinical outcome of endoscopy submucosal dissection with subsequent radiotherapy for esophageal squamous cell carcinoma remain unclear. In this study we aim to investigate the efficacy and safety of endoscopic submucosal dissection with adjuvant radiotherapy in the treatment of superficial esophageal squamous cell carcinoma involving the muscularis mucosae (T1a-MM) or the submucosa < 200 µm (T1b-SM1). METHODS: We analyzed 20 patients with pathologically confirmed T1a-MM or T1b-SM1 esophageal squamous cell carcinoma treated by endoscopic submucosal dissection from 2016 to 2020 in Lihuili Hospital, 9 patients received adjuvant radiotherapy (RT group) and 11 patients received did not (non-RT group). RESULTS: All 20 patients underwent en bloc resection, and both the vertical and horizontal margins were negative. There was no recurrence or lymph node metastasis in the RT group, and no serious complications or death were observed. In the non-RT group, 2 patients had local recurrence and 1 had distant metastasis. None of the 20 patients died of esophageal carcinoma. CONCLUSIONS: Adjuvant radiotherapy following endoscopic submucosal dissection may be a safe and effective method for the treatment of T1a-MM/T1b-SM1 superficial esophageal squamous cell carcinoma.

ZNF468 inhibits irradiation-induced G2/M cell cycle arrest and apoptosis by facilitating AURKA transcription in Esophageal Squamous Cell Carcinoma.

BACKGROUND: ZNF468 is a relatively unexplored gene that has been implicated in potential oncogenic properties in various cancer types. However, the exact role of ZNF468 in radiotherapy resistance of esophageal squamous cell carcinomas (ESCCs) is not well understood. METHODS: Bioinformatic analysis was performed using the TCGA database to assess ZNF468 expression and prognostic significance in pan-cancer and ESCC. Functional experiments were conducted using ZNF468 overexpressing and knockdown cell lines to assess its impact on cell survival, DNA damage response, cell cycle, and apoptosis upon radiation. A luciferase reporter assay was utilized to validate ZNF468 binding to the AURKA promoter. RESULTS: ZNF468 was significantly upregulated in diverse cancer types, including ESCC, and its high expression correlated with adverse prognosis in specific tumors. In the ESCC cohort, ZNF468 exhibited substantial upregulation in post-radiotherapy tissues, indicating its potential role in conferring radiotherapy resistance. Functional experiments revealed that ZNF468 enhances cell viability and facilitates DNA damage repair in radiotherapy-treated ESCC cells, while dampening the G2/M cell cycle arrest and apoptosis induced by radiation. Moreover, ZNF468 facilitated AURKA transcription, resulting in upregulated Aurora A expression, and subsequently inhibited P53 expression, unveiling key molecular mechanisms underlying radiotherapy resistance in ESCC. CONCLUSION: ZNF468 plays an oncogenic role in ESCC and contributes to radiotherapy resistance. It enhances cell survival while dampening radiation-induced G2/M cell cycle arrest and apoptosis. By modulating AURKA and P53 expression, ZNF468 represents a promising therapeutic target for enhancing radiotherapy efficacy in ESCC.