crossing96/oncoscreening huggingface dataset:
METTL3-mediated upregulation of FAM135B promotes EMT of esophageal squamous cell carcinoma via regulating the Wnt/β-catenin pathway.	Family with sequence similarity 135 member B (FAM135B) is a novel driver gene in esophageal squamous cell carcinoma (ESCC). However, little is known regarding its biological functions and mechanisms in ESCC. Here, we identified that the high expression of FAM135B was associated with lymph node metastasis and infiltrating development of ESCC. Elevated FAM135B expression promoted ESCC migration and invasion in vitro and lung metastasis in vivo. Furthermore, epithelial-mesenchymal transition (EMT)-related pathways were enriched in ESCC samples with high levels of FAM135B and FAM135B positively regulated EMT markers. Mechanistically, we observed that FAM135B interacted with the intermediate domain of TRAF2 and NCK-interacting kinase (TNIK), activating the Wnt/β-catenin signaling pathway. The facilitation of TNIK on ESCC migration and invasion was reversed by FAM135B siRNA. In addition, the N6-methyladenosine (m6A) modification positively regulated FAM135B expression, with methyltransferase like 3 (METTL3) acting as its substantial m6A writer. The pro-EMT effects of METTL3 overexpression were reversed by silencing FAM135B. Collectively, these findings illustrate the critical role of ABCDE in ESCC progression and provide new insights into the upstream and downstream mechanisms of FAM135B.NEW & NOTEWORTHY This study reveals for the first time that the novel cancer-related gene, FAM135B, promotes ESCC metastasis both in vitro and in vivo. Besides, we substantiate FAM135B's action on the β-catenin pathway through interacting with TNIK, thereby elucidating the promotional effect of FAM135B on ESCC EMT. Furthermore, we provide initial evidence demonstrating that METTL3-mediated m6A modification upregulates the expression of FAM135B in ESCC cells.	esophagus
[Development and validation of predictive models for esophageal squamous cell carcinoma and its precancerous lesions using terminal motif analysis in circulating cell-free DNA].	Objectives: To develop and validate predictive models for esophageal squamous cell carcinoma (ESCC) using circulating cell-free DNA (cfDNA) terminal motif analysis. The goal was to improve the non-invasive detection of early-stage ESCC and its precancerous lesions. Methods: Between August 2021 and November 2022, we prospectively collected plasma samples from 448 individuals at the Department of Endoscopy, Cancer Hospital, Chinese Academy of Medical Sciences for cfDNA extraction, library construction, and sequencing. We analyzed 201 cases of ESCC, 46 high-grade intraepithelial neoplasia (HGIN), 46 low-grade intraepithelial neoplasia (LGIN), 176 benign esophageal lesions, and 29 healthy controls. Participants, including ESCC patients and control subjects, were randomly assigned to a training set (n=284) and a validation set (n=122). The training cohort underwent z-score normalization of cfDNA terminal motif matrices and a selection of distinctive features differentiated ESCC cases from controls. The random forest classifier, Motif-1 (M1), was then developed through principal component analysis, ten-fold cross-validation, and recursive feature elimination. M1's efficacy was then validated in the validation and precancerous lesion sets. Subsequently, individuals with precancerous lesions were included in the dataset and participants were randomly allocated to newly formed training (n=243), validation (n=105), and test (n=150) cohorts. Using the same procedure as M1, we trained the Motif-2 (M2) random forest model with the training cohort. The M2 model's accuracy was then confirmed in the validation cohort to establish the optimal threshold and further tested by performing validation in the test cohort. Results: We developed two cfDNA terminal motif-based predictive models for ESCC and associated precancerous conditions. The first model, M1, achieved a sensitivity of 90.0%, a specificity of 77.4%, and an area under the curve (AUC) of 0.884 in the validation cohort. For LGIN, HGIN, and T1aN0 stage ESCC, M1's sensitivities were 76.1%, 80.4%, and 91.2% respectively. Notably, the sensitivity for jointly predicting HGIN and T1aN0 ESCC reached 85.0%. Both the predictive accuracy and sensitivity increased in line with the cancer's progression (P＜0.001). The second model, M2, exhibited a sensitivity of 87.5%, a specificity of 77.4%, and an AUC of 0.857 in the test cohort. M2's sensitivities for detecting precancerous lesions and ESCC were 80.0% and 89.7%, respectively, and it showed a combined sensitivity of 89.4% for HGIN and T1aN0 stage ESCC. Conclusions: Two predictive models based on cfDNA terminal motif analysis for ESCC and its precancerous lesions are developed. They both show high sensitivity and specificity in identifying ESCC and its precancerous stages, indicating its potential for early ESCC detection.	esophagus
Substitute or coexistence? Mediastinoscopy-assisted versus thoracoscope-assisted esophagectomy in esophageal cancer: a meta-analysis of perioperative outcomes and long-term survival.	BACKGROUND: Currently, mediastinoscopy-assisted esophagectomy (MAE) and thoracoscope-assisted esophagectomy (TAE) represent two prevalent forms of minimally invasive esophagectomy extensively employed in the management of esophageal cancer (EC). The aim of this meta-analysis is to assess and compare these two surgical approaches concerning perioperative outcomes and long-term survival, offering valuable insights for refining surgical strategies and enhancing patient outcomes in this field. METHODS: Adhering to PRISMA guidelines, the authors systematically searched PubMed, Web of Science, Cochrane Library, Embase, and CNKI databases until 1 March 2024, for studies comparing MAE and TAE. Outcomes of interest included perioperative outcomes (intraoperative outcomes, postoperative recovery, postoperative complications) and survival rates. Statistical analyses were performed using RevMan 5.4, with heterogeneity dictating the use of fixed or random-effects models. RESULTS: A total of 21 relevant studies were finally included. MAE was associated with significantly shorter operation times [mean difference (MD)=-59.58 min, 95% CI: -82.90 to -36.26] and less intraoperative blood loss (MD=-68.34 ml, 95% CI: -130.45 to -6.23). However, MAE resulted in fewer lymph nodes being dissected (MD=-3.50, 95% CI: -6.23 to -0.78). Postoperative recovery was enhanced following MAE, as evidenced by reduced hospital stays and tube times. MAE significantly reduced pulmonary complications [odds ratio (OR)=0.59, 95% CI: 0.44, 0.81] but increased the incidence of recurrent laryngeal nerve injury (OR=1.84, 95% CI: 1.30, 2.60). No significant differences were observed in anastomotic leakage, chylothorax, cardiac complications, wound infections, and gastric retention between MAE and TAE. The long-term survival outcomes showed no statistical difference [hazard ratio (HR)=1.05, 95% CI: 0.71, 1.54]. CONCLUSIONS: MAE offers advantages in reducing operation time, blood loss, and specific postoperative complications, particularly pulmonary complications, with a shorter recovery period compared to TAE. However, it poses a higher risk of recurrent laryngeal nerve injury and results in fewer lymph nodes being dissected. No difference in long-term survival was observed, indicating that both techniques have distinct benefits and limitations. These findings underscore the need for personalized surgical approaches in EC treatment, considering individual patient characteristics and tumor specifics.	esophagus
Risk factors and pattern of metastatic recurrence after endoscopic resection with additional treatment for esophageal cancer.	Although esophageal cancers invading the muscularis mucosa (pT1a-MM) or submucosa (pT1b-SM) after endoscopic resection (ER) are associated with a risk of lymph node metastasis, details of metastatic recurrence after additional treatment remain unknown. We aimed to identify the risk factors for metastatic recurrence and recurrence patterns in patients receiving additional treatment after ER for esophageal cancer. Between 2006 and 2017, patients with pT1a-MM/pT1b-SM esophageal cancer who underwent ER with additional treatment (esophagectomy, chemoradiotherapy [CRT], and radiation therapy) at 21 institutions in Japan were enrolled. We evaluated the risk factors for metastatic recurrence after ER with additional treatment. Subsequently, the rate and pattern (locoregional or distant) of metastatic recurrence were investigated for each additional treatment. Of the 220 patients who received additional treatment, 57, 125, and 38 underwent esophagectomy, CRT, and radiation therapy, respectively. In the multivariate analysis, lymphatic invasion was the sole risk factor for metastatic recurrence after additional treatment (hazard ratio, 3.50; P = 0.029). Although the risk of metastatic recurrence with additional esophagectomy was similar to that with CRT (hazard ratio, 1.01; P = 0.986), the rate of locoregional recurrence tended to be higher with additional esophagectomy (80.0% (4/5) vs. 36.4% (4/11)), leading to a better prognosis in patients with metastatic recurrence after additional esophagectomy than CRT (survival rate, 80.0% (4/5) vs. 9.1% (1/11)). Patients with lymphatic invasion have a high risk of metastatic recurrence after ER with additional treatment for pT1a-MM/pT1b-SM esophageal cancer. Additional esophagectomy may result in a better prognosis after metastatic recurrence.	esophagus
Sirtuin1 (sirt1) regulates the glycolysis pathway and decreases cisplatin chemotherapeutic sensitivity to esophageal squamous cell carcinoma.	We aimed to evaluate the influence of sirtuin1 (sirt1) on the ESCC chemotherapeutic sensitivity to cisplatin. We used ESCC cell ablation sirt1 for establishing a xenograft mouse tumor model. The tumor volume was then detected. sirt1 was over-expressed significantly in ESCC patients and cells. Moreover, sirt1 knockdown raised ESCC sensitivity to cisplatin. Besides, glycolysis was associated with ESCC cell chemotherapy resistance to cisplatin. Furthermore, sirt1 increased ESCC cells' cisplatin chemosensitivity through HK2. Sirt1 enhanced in vivo ESCC chemosensitivity to cisplatin. Overall, these findings suggested that sirt1 knockdown regulated the glycolysis pathway and raised the ESCC chemotherapeutic sensitivity.	esophagus
Impact of bulky loco-regional lymphadenopathy in esophageal adenocarcinoma on survival: a retrospective single center analysis.	The relationship between 'bulky' locoregional lymphadenopathy and survival has not been investigated in the setting of esophageal adenocarcinoma (EAC). This study aimed to explore whether bulky regional lymphadenopathy at diagnosis affected survival outcomes in patients with EAC treated with neoadjuvant chemotherapy and en bloc resection. A single-center retrospective review of a prospectively maintained upper GI cancer surgical database was performed between January 2012 and December 2019. Patients with locally advanced EAC (cT2-3, N+, M0) treated with neoadjuvant docetaxel-based chemotherapy and transthoracic en bloc esophagogastrectomy were identified. Computed tomography scans from before the initiation of treatment were reviewed, and patients were stratified according to whether bulky loco-regional lymph nodes were present. This was defined as lymphadenopathy >2 cm in any axis. Overall survival was compared, and a Cox multivariate regression model was calculated. Two hundred twenty-five of the eight hundred seventy patients identified met the inclusion criteria. Forty-eight (21%) had bulky lymphadenopathy, leaving 177 allocated to the control group. More patients with bulky lymphadenopathy had ypN3 disease (18/48, 38% vs. 39/177, 20%, P = 0.025). Among patients with bulky lymphadenopathy, overall survival was generally worse (32.6 vs. 59.1 months, P = 0.012). However, among the 9/48 (19%) patients with bulky lymphadenopathy who achieved ypN- status survival outcomes were similar to those with non-bulky lymphadenopathy who also achieved lymph node sterilization. Poor differentiation (HR 1.8, 95% CI 1.0-2.9, P = 0.034), ypN+ (HR 1.9, 95% CI 1.1-3.6, P = 0.032), and bulky lymphadenopathy were independently associated with an increased risk of death (HR 1.7, 1.0-2.9, P = 0.048). Bulky regional lymphadenopathy is associated with a poor prognosis. Efforts to identify the ideal treatment regimen for these patients are urgently required.	esophagus
Bemarituzumab plus mFOLFOX6 as first-line treatment in East Asian patients with FGFR2b-overexpressing locally advanced or metastatic gastric/gastroesophageal junction cancer: subgroup of FIGHT final analysis.	BACKGROUND: In the FIGHT study (NCT03694522) bemarituzumab, a humanized monoclonal antibody selective for fibroblast growth factor receptor 2b (FGFR2b), plus mFOLFOX6 showed clinically meaningful efficacy in patients with FGFR2b-positive (2+/3+ membranous staining by immunohistochemistry) locally advanced unresectable/metastatic gastric/gastroesophageal cancer (G/GEJC). A meaningful proportion of patients in FIGHT were enrolled in East Asia, reflecting global epidemiology of G/GEJC. METHODS: This subgroup analysis of the global, phase 2, double-blind FIGHT study included all patients enrolled in East Asian sites. Patients were randomized 1:1 to bemarituzumab-mFOLFOX6 (15 mg/kg and one 7.5 mg/kg dose on cycle 1, day 8) or matching placebo-mFOLFOX6. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate, and safety. Efficacy was evaluated after a minimum follow-up of 24 months. RESULTS: The East Asian subgroup comprised 89 patients (57% of overall study population); 45 were randomized to bemarituzumab-mFOLFOX6 and 44 to placebo-mFOLFOX6. Median PFS (95% confidence interval [CI]) was 12.9 months (8.8-17.9) with bemarituzumab-mFOLFOX6 and 8.2 months (5.6-10.3) with placebo-mFOLFOX6 (HR 0.50, 95% CI 0.29-0.87); median OS (95% CI) was 24.7 months (13.8-33.1) vs 12.9 months (9.3-21.4), respectively (HR 0.56, 95% CI 0.32-0.96). Treatment benefit was more pronounced in patients with FGFR2b-positive G/GEJC in ≥ 10% of tumor cells. No new safety signals were reported. CONCLUSION: In East Asian patients with FGFR2b-positive advanced/metastatic G/GEJC enrolled in the global FIGHT study, bemarituzumab-mFOLFOX6 showed clinically meaningful outcomes over placebo-mFOLFOX6.	esophagus
Latest insights into the global epidemiological features, screening, early diagnosis and prognosis prediction of esophageal squamous cell carcinoma.	As a highly invasive carcinoma, esophageal cancer (EC) was the eighth most prevalent malignancy and the sixth leading cause of cancer-related death worldwide in 2020. Esophageal squamous cell carcinoma (ESCC) is the major histological subtype of EC, and its incidence and mortality rates are decreasing globally. Due to the lack of specific early symptoms, ESCC patients are usually diagnosed with advanced-stage disease with a poor prognosis, and the incidence and mortality rates are still high in many countries, especially in China. Therefore, enormous challenges still exist in the management of ESCC, and novel strategies are urgently needed to further decrease the incidence and mortality rates of ESCC. Although the key molecular mechanisms underlying ESCC pathogenesis have not been fully elucidated, certain promising biomarkers are being investigated to facilitate clinical decision-making. With the advent and advancement of high-throughput technologies, such as genomics, proteomics and metabolomics, valuable biomarkers with high sensitivity, specificity and stability could be identified for ESCC. Herein, we aimed to determine the epidemiological features of ESCC in different regions of the world, especially in China, and focused on novel molecular biomarkers associated with ESCC screening, early diagnosis and prognosis prediction.	esophagus
Radiation pneumonitis prediction with dual-radiomics for esophageal cancer underwent radiotherapy.	BACKGROUND: To integrate radiomics and dosiomics features from multiple regions in the radiation pneumonia (RP grade ≥ 2) prediction for esophageal cancer (EC) patients underwent radiotherapy (RT). METHODS: Total of 143 EC patients in the authors' hospital (training and internal validation: 70%:30%) and 32 EC patients from another hospital (external validation) underwent RT from 2015 to 2022 were retrospectively reviewed and analyzed. Patients were dichotomized as positive (RP+) or negative (RP-) according to CTCAE V5.0. Models with radiomics and dosiomics features extracted from single region of interest (ROI), multiple ROIs and combined models were constructed and evaluated. A nomogram integrating radiomics score (Rad_score), dosiomics score (Dos_score), clinical factors, dose-volume histogram (DVH) factors, and mean lung dose (MLD) was also constructed and validated. RESULTS: Models with Rad_score_Lung&Overlap and Dos_score_Lung&Overlap achieved a better area under curve (AUC) of 0.818 and 0.844 in the external validation in comparison with radiomics and dosiomics models with features extracted from single ROI. Combining four radiomics and dosiomics models using support vector machine (SVM) improved the AUC to 0.854 in the external validation. Nomogram integrating Rad_score, and Dos_score with clinical factors, DVH factors, and MLD further improved the RP prediction AUC to 0.937 and 0.912 in the internal and external validation, respectively. CONCLUSION: CT-based RP prediction model integrating radiomics and dosiomics features from multiple ROIs outperformed those with features from a single ROI with increased reliability for EC patients who underwent RT.	esophagus
Intensive triamcinolone acetonide injection regimen can highly prevent stricture after extensive esophageal endoscopic submucosal dissection.	BACKGROUND: This study aimed to investigate the utility of intensive triamcinolone acetonide (TA) injections after extensive esophageal endoscopic submucosal dissection (ESD). METHODS: This retrospective study included 27 lesions in 27 consecutive patients who underwent ESD (ulcers encompassing ≥3/4 of the esophageal circumference) and received TA injections without oral steroid administration. Groups A and B included patients undergoing ESD with and without complete circumferential resection, respectively. All patients received TA injections (100 mg/session) immediately after ESD. In Group A, weekly based TA injections were performed until near-complete ulcer epithelialization. In Group B, patients did not receive additional injections or received weekly or biweekly TA injections. The primary outcome was stricture rate, and the secondary outcomes were the proportion of patients requiring endoscopic balloon dilation (EBD) and the number of TA injections. RESULTS: Group A included 7 lesions, and Group B included 20 lesions. The median (range) tumor lengths were 40 (30-90) and 45 (30-110) mm in Groups A and B, respectively. In Group A, the median circumferential resection diameter was 40 (20-80) mm. The stricture rate and the proportion of patients requiring EBD were 0 (0%) in Group A and 1 (5.0%) in Group B. The number of TA injection sessions was significantly higher in Group A than in Group B (8 [5-25] vs 1.5 [1-3]; p < 0.001). CONCLUSIONS: Intensive weekly or biweekly based TA injections might aid in preventing post-ESD stricture and the need for EBD in patients undergoing extensive resection involving the entire esophageal circumference.	esophagus
Comparison of proton-based definitive chemoradiotherapy and surgery-based therapy for esophageal squamous cell carcinoma: a multi-center retrospective Japanese cohort study.	BACKGROUND: Proton-based, definitive chemoradiotherapy (P-CRT) for esophageal squamous cell carcinoma (ESCC) previously showed comparable survival outcomes with the surgery-based therapy, i.e., neoadjuvant chemotherapy followed by esophagectomy (NAC-S), in a single-institutional study. This study aimed to validate this message in a Japanese multicenter study. METHODS: Eleven Japanese esophageal cancer specialty hospitals have participated. A total of 518 cases with clinical Stage I-IVA ESCC between 2010 and 2019, including 168 P-CRT and 350 NAC-S patients, were enrolled and long-term outcomes were evaluated. Propensity-score weighting analyses with overlap weighting for confounding adjustment were used. RESULTS: The 3-year overall survival (OS) of the P-CRT group was equivalent to the NAC-S group (74.8% vs. 72.7%, hazard ratio [HR]: 0.87, 95% confidence interval [CI]: 0.61-1.25). Although, the 3-year P-CRT group progression-free survival (PFS) was inferior to the NAC-S group (51.4% vs. 59.6%, HR 1.39, 95% CI 1.04-1.85), the progression P-CRT group cases showed better survival than the NAC-S group (HR 0.58, 95% CI 0.38-0.88), largely because of salvage surgery or endoscopic submucosal dissection for local progression. The survival advantage of P-CRT over NAC-S was more pronounced in the cT1-2 (HR 0.61, 95% CI 0.29-1.26) and cStage I-II (HR 0.50, 95% CI 0.24-1.07) subgroups, although this trend was not evident in other populations, such as cT3-4 and cStage III-IVA. CONCLUSIONS: Proton-based CRT for ESCC showed equivalent OS to surgery-based therapy. Especially for patients with cT1-2 and cStage I-II disease, proton-based CRT has the potential to serve as a first-line treatment.	esophagus
A novel mitochondrial metabolism-related gene signature for predicting the prognosis of oesophageal squamous cell carcinoma.	Oesophageal squamous cell carcinoma (ESCC) is one of the most lethal cancers worldwide. Due to the important role of mitochondrial metabolism in cancer progression, a clinical prognostic model based on mitochondrial metabolism and clinical features was constructed in this study to predict the prognosis of ESCC. Firstly, the mitochondrial metabolism scores (MMs) were calculated based on 152 mitochondrial metabolism-related genes (MMRGs) by single sample gene set enrichment analysis (ssGSEA). Subsequently, univariate Cox regression and LASSO algorithm were used to identify prognosis-associated MMRG and risk-stratify patients. Functional enrichment, interaction network and immune-related analyses were performed to explore the features differences in patients at different risks. Finally, a prognostic nomogram incorporating clinical factors was constructed to assess the prognosis of ESCC. Our results found there were differences in clinical features between the MMs-high group and the MMs-low group in the TCGA-ESCC dataset (P<0.05). Afterwards, we identified 6 MMRGs (COX10, ACADVL, IDH3B, AKR1A1, LIAS, and NDUFB8) signature that could accurately distinguish high-risk and low-risk ESCC patients. A predictive nomogram that combined the 6 MMRGs with sex and N stage to predict the prognosis of ESCC was constructed, and the areas under the receiver operating characteristic (ROC) curve at 1, 2 and 3 years were 0.948, 0.927 and 0.848, respectively. Finally, we found that COX10, one of 6 MMRGs, could inhibit the malignant progression of ESCC in vitro. In summary, we constructed a clinical prognosis model based on 6 MMRGs and clinical features which can accurately predict the prognosis of ESCC patients.	esophagus