crossing96/oncoscreening huggingface dataset:
FKBP Prolyl Isomerase 11: A Novel Oncogene Interacting With SRSF1 in Esophageal Squamous Cell Carcinoma.	Esophageal squamous cell carcinoma (ESCC) is one of the main subtypes of esophageal carcinoma with high morbidity. This study aimed to explore the role of FKBP prolyl isomerase 11 (FKBP11) in ESCC and investigate the underlying mechanism. FKBP11 levels in ESCC tumor tissues and cell lines were measured. Cell function assays were conducted to evaluate the role of FKBP11 in ESCC cells. The xenograft mouse model was established to validate the effect of FKBP11 on ESCC tumorigenesis in vivo. The co-immunoprecipitation assay was performed to determine the FKBP11-interacting proteins. Obvious upregulations in FKBP11 expression were found in ESCC tumor tissues and cell lines. In vitro, FKBP11 knockdown weakened cell proliferation, migration, and invasion capacities and reinforced cell apoptosis in ESCC cells. In vivo, FKBP11 knockdown slowed ESCC tumorigenesis. The following mechanism investigation determined serine and arginine-rich splicing factor 1 (SRSF1) as the FKBP11-interacting protein in ESCC cells. FKBP11 directly bound to SRSF1 and FKBP11 knockdown decreased SRSF1 mRNA level. SRSF1 overexpression abrogated the inhibitory effect of FKBP11 knockdown on the proliferation and migration of ESCC cells. KBP11 functions as an oncogene in ESCC by targeting SRSF1.	esophagus
A-to-I-Edited miR-1304-3p Inhibits Glycolysis and Tumor Growth of Esophageal Squamous Cell Carcinoma by Inactivating Wnt5a/ROR2 Signaling.	A-to-I RNA editing is a pervasive mechanism in the human genome that affects the regulation of gene expression and is closely associated with the pathogenesis of numerous diseases. This study elucidates the regulatory mechanism of A-to-I edited miR-1304-3p in esophageal squamous cell carcinoma (ESCC). Western blot, immunohistochemistry, and RT-qPCR assays were employed to quantify protein and mRNA expression. Colony formation, Edu, wound healing, and Transwell assays were applied to determine miRNA function. Glycolysis was assessed using glucose uptake and lactate production assay. A dual-luciferase reporter assay confirmed the downstream targets of miRNA, and a xenograft assay demonstrated the efficacy of the miRNA. The A-to-I RNA editing level of miR-1304-3p was observed to increase in KYSE180 and KYSE140 ESCC cells following ADAR1 treatment. Following A-to-I editing, the function of miR-1304-3p in ESCC progression underwent a reversal, shifting from carcinogenic to inhibitory. Wild-type (WT) miR-1304-3p targets IRS1, whereas the edited version targets ROR2. The WT miR-1304-3p, but not the edited version, suppressed the expression and tumor-suppressive effect of IRS1 in ESCC. Conversely, ROR2, a specific downstream target of the edited miR-1304-3p, acted as a tumor promoter in ESCC. Furthermore, A-to-I editing of miR-1304-3p can inhibit glycolysis and inactivate the Wnt5a/ROR2 signaling pathway in ESCC. A-to-I RNA editing alters the function of miR-1304-3p in ESCC by changing its target gene. The edited miR-1304-3p hinders the development of ESCC by inhibiting glycolysis and inactivating the Wnt5a/ROR2 signaling pathway.	esophagus
Comparison of mediastinoscopy and thoracoscope minimally invasive esophagectomy in the treatment of esophageal cancer: a meta-analysis and system review.	OBJECTIVE: The efficacy and safety of transcervical inflatable mediastinoscopic esophagectomy (TIME) in the treatment of esophageal cancer are unclear. The objective of this meta-analysis was to evaluate the efficacy and safety of TIME treatment for esophageal cancer and to compare it with thoracoscopic assisted minimally invasive esophagectomy (TAMIE) for the treatment of esophageal cancer. METHODS: A literature search was performed using PubMed, Embase, and the Cochrane Library to retrieve articles published up to January 2024 to comparatively assess studies of TIME and TAMIE. Meta-analysis was performed using randomized/fixed-effects models and heterogeneity was assessed. RESULTS: A total of 819 patients were included in the nine studies herein. Among them, 409 patients with esophageal cancer underwent mediastinoscopy-assisted esophagectomy, and 410 patients with esophageal cancer underwent thoracolaparoscopy-assisted esophagectomy. There was no statistical difference between the TIME and TAMIE groups in intraoperative bleeding, incidence of anastomotic fistula, chylothorax, postoperative bleeding, arrhythmia, postoperative complications and in-hospital mortality. In addition, the operative time in the TIME group, 3-day postoperative induced flux, postoperative hospitalization time, number of lymph node dissection, and incidence of pulmonary complications were smaller than those in the TAMIE group, and the differences were all statistically significant. However, in terms of the incidence of recurrent laryngeal nerve injury (including hoarseness), the TIME group was higher than the TAMIE group. CONCLUSION: TIME is a safe and feasible alternative to TAMIE for the treatment of resectable esophageal cancer, but further randomized studies are needed to better assess the long-term benefits of TIME compared with TAMIE.	esophagus
Human Epidermal Growth Factor Receptor 2 Positive Advanced Gastric or Esophagogastric Adenocarcinoma: Reflecting on the Past to Gain a New Insights.	PURPOSE OF REVIEW: Human epidermal growth factor receptor 2 (HER2) is a critical target in advanced gastric cancer (AGC). This review highlights the current treatment landscape, lessons learned from past clinical trials, and prospects for future treatment strategies for HER2-positive AGC. RECENT FINDINGS: Trastuzumab had been the standard treatment for HER2-positive AGC for a decade, and subsequently, trastuzumab deruxtecan, an antibody-drug conjugate (ADC), emerged with an impressive response. Recently, the addition of pembrolizumab to first-line chemotherapy plus trastuzumab has become a novel standard treatment. Past clinical trials of HER2-targeted therapies, which succeeded in HER2-positive breast cancer but failed in AGC, have deepened our understanding of resistance mechanisms. Based on these results, several clinical trials of novel HER2-targeted therapies, including immunologic approaches such as CAR-T cells and vaccines, are currently ongoing. Circulating tumor DNA is also expected to be a tool for real-time biomarker analysis. Additionally, ADCs with a bystander effect have the potential to expand the scope of HER2-targeted therapies to HER2-expressing, including HER2-low AGC. Learning from past trials, further development of novel HER2-targeted therapies is underway, expanding their scope to HER2-expressing AGC. Meanwhile, selecting optimal treatment is a challenging issue in cases with HER2-low AGC overlapping with other biomarkers like CLDN18.2.	esophagus
Constructing individualized follow-up strategies for locally advanced esophageal squamous cell carcinoma patients based on dynamic recurrence risk changes.	The aim of this study was to explore the high-risk factors for recurrence in patients with locally advanced esophageal squamous cell carcinoma (ESCC) undergoing definitive chemoradiotherapy or radiotherapy (dCRT or dRT). Conditional survival (CS) was used to evaluate the dynamic survival and recurrence risk of patients after treatment, and individualized monitoring strategies were developed for patients. Logistic regression analysis was performed to determine independent recurrence risk factors. Calibration curves and receiver operating characteristic (ROC) curve were used to evaluate nomogram models. Kaplan-Meier curves were used to compare survival rates in different groups and to calculate CS rate. A total of 677 patients were included. Multivariate logistic analyses demonstrated that chemotherapy cycles, tumor length, body mass index (BMI), platelet-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio (LMR) were independent recurrence risk factors (p < 0.05). Subsequently, we constructed nomogram models to predict recurrence and risk stratification. Kaplan-Meier curves showed that conditional locoregional recurrence-free survival and distant metastasis-free survival of patients in different risk groups and clinical stages progressively increased with survival time, whereas local recurrence and distant metastasis annual recurrence rates decreased yearly with increasing survival time. Finally, we developed an individualized follow-up strategy based on CS at different frequencies. Individualized follow-up strategies developed on the basis of CS can better monitor the changes in patients' conditions and contribute to timely salvage treatment and rational allocation of healthcare resources.	esophagus
Diagnostic value of multi-tumor-associated autoantibody expression in esophageal squamous cell carcinoma and correlation of clinical features.	OBJECTIVE: This study aimed to investigate the diagnostic value of 7-tumor associated autoantibodies (7-TAAB) and to evaluate the relationship between 7-TAAB and clinical features in esophageal squamous cell carcinoma (ESCC), which can be used to guide clinical diagnosis and treatment and achieve its clinical value. METHODS: (1) Blood specimens were collected from patients with ESCC who had not previously received antitumor therapy (ESCC group) and those who had normal medical check-ups in the hospital during the same period (control group). The concentrations of 7-TAAB (P53, PGP9.5, SOX2, GAGE7, GBU4-5, MAGE A1, and CAGE) in serum were determined by enzyme-linked immunosorbent assay. The concentrations of 7-TAAB were compared between the ESCC and control groups, and the positive rate of 7-TAAB was calculated to determine the sensitivity, specificity, and accuracy of 7-TAAB. The diagnostic value of 7-TAAB was analyzed using the receiver operating characteristic (ROC) curve. (2) The clinical data of patients with ESCC were collected and the correlation between the rate of 7-TAAB and clinical features was analyzed. RESULTS: (1) The serum levels and positivity rates of five antibodies (PGP9.5, SOX2, GBU4-5, MAGE-A1, and CAGE) were higher in the ESCC group than in the control group (P < 0.05) and the positive expression rate of the combined serum 7-TAAB in the ESCC group was significantly higher than that in the control group (P < 0.05). (2) The sensitivity of single antibody detection was 4.20%-17.65%, with a specificity of 96.49%-100%, and accuracy of 51.07%-57.94%. The sensitivity of 7-TAAB combined detection was 49.58%, the specificity was 92.98%, and the accuracy was 70.81%. (3) The ROC curve showed that the 7-TAAB combined test had a certain diagnostic value for ESCC and that its diagnostic efficacy was significantly higher than that of the single autoantibody tests. The diagnostic efficacy of the combined test with the remaining five antibodies (PGP9.5, SOX2, GBU4-5, MAGE-A1, and CAGE) was similar to that of the 7-TAAB combined test after eliminating the two antibodies with low expression rates. (4) Univariate analysis revealed significant differences in the positive expression rates of the 7-TAAB combination test in terms of age, hemoglobin level, albumin level, tumor location, tumor length, lymph node stage, and tumor clinical stage (P < 0.05), and multivariate analysis revealed that age and lymph node stage were independent factors affecting antibody expression. CONCLUSION: The multi-tumor-associated autoantibody combination test not only has a good auxiliary diagnostic value but also closely correlates with the clinical features of ESCC.	esophagus
Efficacy and safety of S-1 plus oxaliplatin combined with apatinib and camrelizumab as neoadjuvant therapy for patients with locally advanced gastric or gastroesophageal junction adenocarcinoma: a protocol for a single-arm phase II trial.	Gastric cancer, as the fifth most diagnosed malignancy and the fourth leading cause of cancer-related death globally, remains a significant health concern. The potential effect of the programmed death-1 (PD-1) inhibitor, when used alongside chemotherapy and antiangiogenic agents in neoadjuvant therapy for gastric cancer, has yet to be explored in the published literature. This study aims to evaluate the efficacy and safety of the S-1 plus oxaliplatin (SOX) regimen when combined with apatinib and camrelizumab (SOXAC) as neoadjuvant therapy for patients with locally advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma. A single-arm, open-label, single-center phase II clinical trial has been designed to evaluate the safety and efficacy of the SOXAC regimen as neoadjuvant therapy for patients diagnosed with locally advanced gastric or GEJ adenocarcinoma (cT2-3N + M0 or T4NxM0). Eligible patients are to receive 2 cycles of SOXAC and 1 cycle of SOX regimen with camrelizumab (SOXC) as neoadjuvant therapy prior to radical surgery, and 3 cycles of SOXC as postoperative adjuvant therapy. The primary endpoint is major pathological remission (MPR), while secondary endpoints include pathological complete response (pCR) rate, R0 resection rate, objective response rate (ORR), operation-related outcomes, and safety. The SOX regimen remains a leading choice for neoadjuvant chemotherapy in Eastern countries. Recent studies suggest that combining chemotherapy, targeted agents, and immune checkpoint inhibitors can enhance the antitumor immune response. This phase II clinical trial seeks to assess the safety and efficacy of the SOXAC regimen as neoadjuvant therapy for patients with locally advanced resectable gastric or GEJ adenocarcinoma, while also exploring the correlation between biomarkers and efficacy.Trial Registration Chinese Clinical Trial Registry (ChiCTR): ChiCTR2200062285 ( https://www.chictr.org.cn/ ).	esophagus
D-loop mutations in mitochondrial DNA are a risk factor for chemotherapy resistance in esophageal cancer.	Esophageal cancer is a highly aggressive disease, and acquired resistance to chemotherapy remains a significant hurdle in its treatment. mtDNA, crucial for cellular energy production, is prone to mutations at a higher rate than nuclear DNA. These mutations can accumulate and disrupt cellular function; however, mtDNA mutations induced by chemotherapy in esophageal cancer remain unexplored. We aimed to identify such mutations in esophageal cancer, pre- and post-chemotherapy, and explore the relationship between them and clinicopathological factors associated with chemotherapy resistance. We investigated mtDNA mutations in Human esophageal squamous cell carcinoma (ESCC) cancer cell lines (TE8 and TE11) and patient samples (27 pre- and post-chemotherapy, and 96 post-chemotherapy) using next-generation sequencing. Our analysis revealed a rise in mtDNA mutations following chemotherapy, particularly within the D-loop region. Moreover, mutations in a specific D-loop segment (hypervariable segment 1; HVS1) were associated with lower mtDNA copy number, poorer response to chemotherapy, and decreased five-year survival rates. These findings suggest that HVS1 mutations in mtDNA acquired after chemotherapy may contribute to treatment resistance and poorer clinical outcomes in patients with esophageal cancer. This study sheds light on the mechanisms of chemotherapy resistance and provides valuable insights for future research to overcome this challenge.	esophagus
Adiposity and risks of gastrointestinal cancers: A 10-year prospective study of 0.5 million Chinese adults.	Associations of adiposity with risks of oesophageal squamous cell carcinoma (ESCC) and non-cardia stomach cancer, both prevalent in China, are still inconclusive. While adiposity is an established risk factor for colorectal cancer, the relevance of fat-free mass and early-adulthood adiposity remains to be explored. The prospective China Kadoorie Biobank study included 0.5 million adults (aged 30-79 years) from 10 areas in China. Participants' body size and composition were measured at baseline and at resurveys (amongst a subset). After >10 years of follow-up, 2350, 3345 and 3059 incident cases of oesophageal (EC), stomach (SC) and colorectal (CRC) cancers were recorded, respectively. Cox regression was used to estimate hazard ratios (HRs) for these cancers in relation to different adiposity traits. General and central adiposity were inversely associated with EC (primarily ESCC) risk, with HRs of 0.81 (95% CI 0.77-0.85), 0.76 (0.72-0.81) and 0.87 (0.83-0.92) per SD increase in usual levels of BMI, body fat percentage (BF%) and waist circumference (WC), respectively. Adiposity was also inversely associated with SC risk [HR = 0.79 (0.75-0.83) and 0.88 (0.84-0.92) per SD increase in usual BF% and WC], with heterogeneity by cardia and non-cardia subsites, and positively associated with CRC [HR = 1.09 (1.03-1.15) and 1.17 (1.12-1.22) per SD higher usual BF% and WC]. Fat-free mass was inversely associated with EC [HR = 0.93 (0.89-0.98) per SD increase] but positively associated with CRC [1.09 (1.04-1.14)], while BMI at age 25 was positively associated with all three cancers. After mutual adjustment, general adiposity remained inversely associated with EC and SC, while central adiposity remained positively associated with CRC.	esophagus
Younger age as an independent factor for second primary head and neck cancer in esophageal squamous cell carcinoma patients after curative esophagectomy: A two-center retrospective study.	BACKGROUND: Postoperative survival of esophageal cancer patients has improved with advances in technology and treatment modalities. However, squamous cell carcinoma (SCC) often affects the esophagus together with the head and neck regions, with second primary head and neck cancer (SPHNC) adversely influencing the patients' quality of life. Therefore, patients with esophageal squamous cell carcinoma (ESCC) should be carefully followed up postoperatively. This study evaluated the risk of developing SPHNCs after an esophagectomy for ESCC. METHODS: Patients with ESCC who underwent curative esophagectomy from January 2008 to December 2017 from two tertiary medical centers, Taipei Veteran General Hospital and Kaohsiung Veteran General Hospital, were retrospectively reviewed. SPHNC development was documented according to the anatomic region and the cumulative incidence rate and risk factors were analyzed. RESULTS: The median follow-up period of the 435 patients included in our study was 48.5 months [interquartile range (IQR) 16.7-92.4 months]. Among the ESCC patients after curative esophagectomy, younger age <50 [hazard ratio 4.13, 95% CI: 2.53-6.75, p < 0.001) was the only independent factor for developing SPHNCs in the multivariable analysis. The cumulative incidence rate of SPHNCs of patients aged <50 years old was 14.3%, 22.1%, and 34.2% after 3, 5, and 10 years, respectively. CONCLUSIONS: There was a high risk of secondary cancer after ESCC in the upper aerodigestive tract, especially the head and neck regions; therefore, active surveillance is strongly recommended, especially in younger patients.	esophagus
Re-evaluation of the relationship between PrPc expression and patient prognosis in primary esophageal squamous cell carcinoma and primary hepatocellular carcinoma.	PrPc is expressed in various tumors and is associated with cancer progression, but previous studies have shown conflicting results regarding its relationship with patient prognosis-potentially due to differences in the antibodies used. This study aimed to clarify the relationship between PrPc expression and primary esophageal squamous cell carcinoma (ESCC) and primary hepatocellular carcinoma (HCC) using a novel anti-PrPc antibody, 4AA-m, noted for its high specificity and sensitivity. We used flow cytometry to detect PrPc expression in ESCC and HCC cell lines. Immunohistochemistry with 4AA-m was then performed on tissue microarrays from 179 patients with primary ESCC and 92 patients with primary HCC. PrPc expression was semi-quantitatively assessed using the Tumor-DAB-H-Score, and its association with tumor prognosis was analyzed. In ESCC, PrPc expression was negatively correlated with lymph node metastasis, and patients with high PrPc expression had better overall survival compared to those with low expression. PrPc expression was identified as an independent prognostic factor for overall survival in ESCC. In HCC, patients with positive PrPc expression had shorter recurrence-free survival (RFS) than those without PrPc expression. PrPc expression was also found to be an independent prognostic factor for RFS in HCC.	esophagus
Prognostic Impact of Tumor Cell Nuclear Size Assessed by Artificial Intelligence in Esophageal Squamous Cell Carcinoma.	Tumor cell nuclear size (NS) indicates malignant potential in breast cancer; however, its clinical significance in esophageal squamous cell carcinoma (ESCC) is unknown. Artificial intelligence (AI) can quantitatively evaluate histopathological findings. The aim was to measure NS in ESCC using AI and elucidate its clinical significance. We investigated the relationship between NS assessed by AI and prognosis in 138 patients with ESCC who underwent curative esophagectomy. Hematoxylin and eosin-stained slides from the deepest tumor sections were digitized. Using HALO-AI DenseNet v2, we created a deep-learning classifier that identified tumor cells with an NS area >20 μm(2). Median NS was 40.14 μm(2), which was used to divide patients into NS-high and NS-low groups (n = 69 per group). Five-year overall survival (OS) and relapse-free survival rates were significantly lower in the NS-high group (43.2% and 39.6%) than in the NS-low group (67.7% and 49.6%). Multivariate analysis showed that greater tumor depth and NS-high status (hazard ratio: 1.79; P = .032) were independent risk factors for OS. In 77 cases with neoadjuvant chemotherapy, increased tumor depth and NS-high status (hazard ratio: 1.99; P = .048) were independent prognostic factors for unfavorable OS. Compared with the NS-low group, the NS-high group had significantly higher anisokaryosis, higher Ki-67 expression as calculated by AI analysis of immunostaining, and higher NS heterogeneity as examined by equidividing the tumors into square tiles. In conclusion, NS assessed by AI is a simple and useful prognostic factor for ESCC.	esophagus
Therapy response monitoring in blood plasma from esophageal adenocarcinoma patients using cell-free DNA methylation profiling.	Esophageal adenocarcinoma (EAC) is an aggressive cancer characterized by a high risk of relapse post-surgery. Current follow-up methods (serum carcinoembryonic antigen detection and PET-CT) lack sensitivity and reliability, necessitating a novel approach. Analyzing cell-free DNA (cfDNA) from blood plasma emerges as a promising avenue. This study aims to evaluate the cost-effective and genome-wide cell-free reduced representation bisulfite sequencing (cfRRBS) method combined with computational deconvolution for effective disease monitoring in EAC patients. cfDNA methylation profiling with cfRRBS was performed on 162 blood plasma samples from 33 EAC cancer patients and 28 blood plasma samples from 20 healthy donors. The estimated tumor fraction for EAC patients at the time of diagnosis was significantly different from the healthy donor plasma samples (one-sided Wilcoxon rank-sum test: p-value = 0.032). Tumor fractions above 15% and focal gains/amplifications in MYC (chr8), KRAS (chr12), EGFR (chr7) and NOTCH2 (chr1) were observed in four samples of distinct patients at the time metastatic disease was detected. This study showed feasibility to estimate tumor fractions in blood plasma of EAC patients based on cfDNA methylation using cfRRBS and computational deconvolution. Nevertheless, in this study only cancer patients with evidence of metastatic disease show high tumor fractions and copy number alterations.	esophagus