crossing96/oncoscreening huggingface dataset:
CstF64-Induced Shortening of the BID 3'UTR Promotes Esophageal Squamous Cell Carcinoma Progression by Disrupting ceRNA Cross-talk with ZFP36L2.	The majority of human genes have multiple polyadenylation sites, which are differentially used through the process of alternative polyadenylation (APA). Dysregulation of APA contributes to numerous diseases, including cancer. However, specific genes subject to APA that impact oncogenesis have not been well characterized, and many cancer APA landscapes remain underexplored. Here, we used dynamic analyses of APA from RNA-seq (DaPars) to define both the 3'UTR APA profile in esophageal squamous cell carcinoma (ESCC) and to identify 3'UTR shortening events that may drive tumor progression. In four distinct squamous cell carcinoma datasets, BID 3'UTRs were recurrently shortened and BID mRNA levels were significantly upregulated. Moreover, system correlation analysis revealed that CstF64 is a candidate upstream regulator of BID 3'UTR length. Mechanistically, a shortened BID 3'UTR promoted proliferation of ESCC cells by disrupting competing endogenous RNA (ceRNA) cross-talk, resulting in downregulation of the tumor suppressor gene ZFP36L2. These in vitro and in vivo results were supported by human patient data whereby 3'UTR shortening of BID and low expression of ZFP36L2 are prognostic factors of survival in ESCC. Collectively, these findings demonstrate that a key ceRNA network is disrupted through APA and promotes ESCC tumor progression.Significance: High-throughput analysis of alternative polyadenylation in esophageal squamous cell carcinoma identifies recurrent shortening of the BID 3'UTR as a driver of disease progression.	esophagus
Inflammation and nutrition-based biomarkers in the prognosis of oesophageal cancer: a systematic review and meta-analysis.	BACKGROUND: Accumulating literature has shown the predictive values of inflammation and nutrition-based biomarkers in the prognosis of oesophageal cancer but with inconsistent findings. METHOD: We performed a meta-analysis to systematically evaluate the predictive value of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), C reactive protein-to-albumin ratio (CAR), systemic inflammation index (SII), prognostic nutritional index (PNI), Glasgow Prognostic Score (GPS) and modified Glasgow Prognostic Score (mGPS) in oesophageal cancer. The outcome indicators include the overall survival (OS), disease-free survival (DFS) and cancer-specific survival (CSS). We applied pooled HR, sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and area under the curve together with 95% CI to estimate the predictive accuracy. RESULTS: A total of 72 studies, including 22 260 patients, were included in the meta-analysis. Elevated NLR, PLR CAR, SII, GPS, mGPS and decreased LMR and PNI were associated with poor OS of oesophageal cancer. A high level of NLR, PLR and GPS was related to poor DFS. A high level of NLR and GPS was related to poor CSS. The summarised AUC of CAR (0.72, 95% CI: 0.68 to 0.75) and mGPS (0.75, 95% CI: 0.71 to 0.78) surpassed any other indicators. CONCLUSIONS: Clinical indicators such as NLR, PLR, LMR, PNI, SII, CAR, GPS and mGPS have the moderate predictive ability in OS, DFS and CSS of oesophageal cancer. The pretreatment level of CAR and mGPS showed an outstanding prediction value in 5-year OS for oesophageal cancer.	esophagus
Impact of Frailty on Treatment Outcome in Patients With Locally Advanced Esophageal Cancer Undergoing Concurrent Chemoradiotherapy.	BACKGROUND/AIM: The clinical significance of frailty status on treatment outcome in patients with esophageal cancer (EC) has been seldom explored. This study aimed to evaluate the impact of pretreatment frailty on treatment-related toxicity and survival outcome in patients with EC undergoing concurrent chemoradiotherapy (CCRT). PATIENTS AND METHODS: Patients aged ≥20 years and with newly diagnosed locally advanced EC receiving neoadjuvant radiotherapy and concurrent chemotherapy with weekly administration of carboplatin and paclitaxel for 5 weeks were prospectively enrolled. A pretreatment frailty assessment was performed within 7 days before CCRT initiation. The primary endpoint was treatment-related toxicity and complications of CCRT while the secondary endpoint was overall survival. RESULTS: A total of 87 patients were enrolled, 41 (47%) and 46 (53%) of whom were allocated in the frail and fit group, respectively. Frail patients had a significantly higher incidence of having at least one severe hematological adverse event (63.4% vs. 19.6%, p<0.001), higher risk of emergent room visiting [relative risk 3.72; 95% confidence interval (CI)=1.39-9.91; p=0.009] and hospitalization (relative risk 3.85; 95% CI=1.03-11.2; p=0.013) during the course of CCRT, when compared to fit patients. Overall survival showed significant worsening in the frail group [adjusted hazard ratio (HR)=2.12; 95% CI=1.01-4.42; p=0.046]. CONCLUSION: Frailty is associated with increase of treatment-related toxicities and poor survival outcome in EC patients undergoing CCRT. Our study suggested that pretreatment frailty assessment is imperative to serve as a predictor and prognostic factor for all adult patients with EC undergoing CCRT.	esophagus
Extending treatment criteria for Barrett's neoplasia: results of a nationwide cohort of 138 endoscopic submucosal dissection procedures.	BACKGROUND: The use of endoscopic submucosal dissection (ESD) is gradually expanding for treatment of neoplasia in Barrett's esophagus (BE). We aimed to report outcomes of all ESDs for BE neoplasia performed in the Netherlands. METHODS: Retrospective assessment of outcomes, using treatment and follow-up data from a joint database. RESULTS: 130/138 patients had complete ESDs, with 126/130 (97 %) en bloc resections. Median (interquartile range (IQR)) procedure time was 121 minutes (90-180). Pathology findings were high grade dysplasia (HGD) (5 %) or esophageal adenocarcinoma (EAC) T1a (43 %) or T1b (52 %; 19 % sm1, 33 % ≥ sm2). Among resections of HGD or T1a EAC lesions, 87 % (95 %CI 75 %-92 %) were both en bloc and R0; the corresponding value for T1b EAC lesions was 49 % (36 %-60 %). Among R1 resections, 10/34 (29 %) showed residual cancer, all detected at first endoscopic follow-up. The remaining 24 patients (71 %) showed no residual neoplasia. Six of these patients underwent surgery with no residual tumor; the remaining 18 underwent endoscopic follow-up during median 31 months with 1 local recurrence (annual recurrence rate 2 %). Among R0 resections, annual local recurrence rate during median 27 months was 0.5 %. CONCLUSION: In expert hands, ESD allows safe removal of bulky intraluminal neoplasia and submucosal cancer. ESD of the latter showed R1 resection margins in 50 %, yet only one third had persisting neoplasia at follow-up. To better stratify R1 patients with an indication for additional surgery, repeat endoscopy after healing of the ESD might be a helpful possible prognostic factor for residual cancer.	esophagus
Significance of Antimicrobial Prophylaxis for the Prevention of Early-Onset Pneumonia After Radical Esophageal Cancer Resection: A Retrospective Analysis of 356 Patients Undergoing Thoracoscopic Esophagectomy.	BACKGROUND: Postoperative pneumonia is a common complication after esophagectomy and is associated with a high mortality rate. Although many randomized, controlled trials have been conducted on the prevention of postoperative pneumonia, little attention has been paid to the efficacy of antimicrobial prophylaxis. The purpose of this study was to investigate the impact of antimicrobial prophylaxis on the prevention of postoperative pneumonia. METHODS: Data of patients with esophageal cancer who underwent thoracoscopic esophagectomy between 2016 and 2020 were collected. Early-period patients received cefazolin (CEZ) per protocol as antimicrobial prophylaxis (n = 250), and later-period patients received ampicillin/sulbactam (ABPC/SBT) (n = 106) because of the unavailability of CEZ in Japan. The incidence of pneumonia was compared between treatments in this quasi-experimental setting. Pneumonia detected by routine computed tomography (CT) on postoperative Days 5-6 was defined as early-onset pneumonia, and pneumonia that developed later was defined as late-onset pneumonia. RESULTS: The incidence of early-onset pneumonia was significantly lower (3.8% vs. 13.6%, P = 0.006), and the median length of postoperative hospital stay was significantly shorter (17 vs. 20 days, P < 0.001) in the ABPC/SBT group than in the CEZ group. The incidence of late-onset pneumonia was similar between groups (9.4% vs. 10.0%, P = 0.870). The incidence of Clostridioides difficile infections and the incidence of multidrug-resistant organisms were similar between groups. Multivariate analyses consistently showed the superiority of ABPC/SBT to CEZ in preventing early-onset pneumonia (odds ratio: 0.20, P = 0.006). CONCLUSIONS: ABPC/SBT after esophagectomy was better at preventing early-onset pneumonia compared with CEZ and was feasible regarding the development of antimicrobial resistance.	esophagus
A multi-omics study delineates new molecular features and therapeutic targets for esophageal squamous cell carcinoma.	Esophageal squamous cell carcinoma (ESCC) is a major histological subtype of esophageal cancer with inferior prognosis. Here, we conducted comprehensive transcriptomic, proteomic, phosphoproteomic, and metabolomic characterization of human, treatment-naive ESCC and paired normal adjacent tissues (cohort 1, n = 24) in an effort to identify new molecular vulnerabilities for ESCC and potential therapeutic targets. Integrative analysis revealed a small group of genes that were related to the active posttranscriptional and posttranslational regulation of ESCC. By using proteomic, phosphoproteomic, and metabolomic data, networks of ESCC-related signaling and metabolic pathways that were closely linked to cancer etiology were unraveled. Notably, integrative analysis of proteomic and phosphoproteomic data pinpointed that certain pathways involved in RNA transcription, processing, and metabolism were stimulated in ESCC. Importantly, proteins with close linkage to ESCC prognosis were identified. By enrolling an ESCC patient cohort 2 (n = 41), three top-ranked prognostic proteins X-prolyl aminopeptidase 3 (XPNPEP3), bromodomain PHD finger transcription factor (BPTF), and fibrillarin (FBL) were verified to have increased expression in ESCC. Among these prognostic proteins, only FBL, a well-known nucleolar methyltransferase, was essential for ESCC cell growth in vitro and in vivo. Furthermore, a validation study using an ESCC patient cohort 3 (n = 100) demonstrated that high FBL expression predicted unfavorable patient survival. Finally, common cancer/testis antigens and established cancer drivers and kinases, all of which could direct therapeutic decisions, were characterized. Collectively, our multi-omics analyses delineated new molecular features associated with ESCC pathobiology involving epigenetic, posttranscriptional, posttranslational, and metabolic characteristics, and unveiled new molecular vulnerabilities with therapeutic potential for ESCC.	esophagus
CircIMMP2L promotes esophageal squamous cell carcinoma malignant progression via CtBP1 nuclear retention dependent epigenetic modification.	BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers. The two major lethal causes of ESCC are diagnosis at an advanced stage and lymph node metastasis (LNM). Circular RNAs (circRNAs) play critical regulatory roles in cancer progression, though, largely through unclear mechanisms. However, the character of circRNAs in the malignant progression of ESCC remains unclear. METHODS: The circRNA microarray was used to explore the circRNAs that were differentially expressed between ESCC and paired adjacent normal tissues. The function of circIMMP2L was validated by gain or loss of function assays. Pull-down, RNA immunoprecipitation assays were used to demonstrate the biological mechanism of circIMMP2L. Tissue microarray (TMA), specimen, and paired plasma were investigated to evaluate the clinical significance of circIMMP2L. RESULTS: CircIMMP2L, commonly upregulated in tumor and plasma from advanced-stage ESCC patients and LNM patients, predicts poorer patient survival. CircIMMP2L was also found to be a significant indicator for LNM, even in the T1 stage of ESCC. CircIMMP2L depletion suppressed the malignant progression of ESCC both in vitro and in vivo. Mechanistically, cytoplasmic circIMMP2L interacted with CtBP1 and facilitated the nuclear retention of CtBP1 in a CtBP2-independent manner. Moreover, circIMMP2L promoted the interaction of CtBP1 with HDAC1 in the nucleus, which is essential for epigenetic remodeling and transcriptional suppression of E-cadherin and p21. CONCLUSIONS: These findings demonstrated that circIMMP2L promotes the malignant progression of ESCC mediated by CtBP1 nuclear retention and is a robust biomarker for the diagnosis, prognosis, and LNM in ESCC. Further, the findings extend our knowledge about the mechanism of circRNA regulation of gene transcription through epigenetics.	esophagus
Preoperative transferrin level is a novel indicator of short- and long-term outcomes after esophageal cancer surgery.	BACKGROUND: This study aimed to examine whether preoperative serum transferrin, a rapid-turnover protein, correlates with short- and long-term outcomes after esophagectomy. METHODS: Preoperative transferrin levels, calculated by summing serum iron and unsaturated iron-binding capacity, were evaluated in 224 patients who underwent esophagectomy for stage I-III esophageal cancer without preoperative treatment. Transferrin levels are directly proportional to total iron-binding capacity (TIBC), and we defined TIBC < 250 μg/dL as low transferrin. We evaluated the relationship between preoperative transferrin levels and short- and long-term outcomes after esophagectomy using univariate and multivariate Cox proportional hazards analyses. RESULTS: Of all patients, 25 (11.2%) had low preoperative transferrin levels. Low preoperative transferrin levels were strongly correlated with worse preoperative performance status, advanced pathological T stage, and more open esophagectomy (p = 0.0078, 0.0001, and 0.013, respectively). Patients with low preoperative transferrin levels experienced significantly more frequent postoperative pneumonia in univariate and multivariate analysis [hazard ratio (HR) 3.30, 95% confidence interval (CI) 1.032-10.033, p = 0.0443]. Additionally, these patients were significantly correlated with worse overall survival (OS) in univariate and multivariate analyses (HR 2.75, 95% CI 1.018-7.426, p = 0.0460). Furthermore, we investigated the relationship between OS and postoperative pneumonia to elucidate why low preoperative transferrin, which is an independent risk factor for postoperative pneumonia, leads to poor prognosis. Patients with postoperative pneumonia were strongly associated with a shorter OS (p = 0.0099). CONCLUSION: Preoperative serum transferrin levels may be a novel indicator of postoperative pneumonia and OS after esophagectomy.	esophagus
Clinical Relevance of Tissue and Serum Human Epidermal Growth Factor Receptor 2 Expression in Patients With Esophageal Squamous Cell Carcinoma.	BACKGROUND: Serum and tissue human epidermal growth factor receptor 2 (HER2) levels were evaluated in resected esophageal squamous cell carcinoma (SCC) specimens to assess the relationship between HER2 expression and long-term prognosis. METHODS: We included 95 patients who underwent esophagectomy for esophageal SCC. The serum HER2-extracellular domain (sHER2-ECD) levels were measured using an ELISA kit. A time-dependent receiver operating characteristics curve for censored survival outcomes was constructed to estimate the optimal cut-off value of sHER2-ECD (set at 4211 pg/mL). Immunohistochemical (IHC) staining was performed for HER2, and specimens were classified based on low (0 or 1+) or high HER2-IHC expression (2+ or 3+). RESULTS: Patients with low sHER2-ECD levels showed poorly differentiated tumors, nodal involvement, and larger tumor size more frequently compared to patients with high sHER2-ECD levels. There were no differences in clinicopathological features based on HER2-IHC expression. Between patients with high and low HER2-IHC expression, the former group showed significantly higher sHER2-ECD levels. Patients with high sHER2-ECD levels had significantly favorable relapse-free survival (RFS) and overall survival (OS) compared to those with low sHER2-ECD levels. Conversely, patients with high HER2-IHC expression had significantly poorer RFS than did patients with low HER2-IHC expression, although no difference was observed in OS. Additionally, patients with high sHER2-ECD levels and low HER2-IHC expression had the highest OS and RFS among the patients studied. CONCLUSIONS: The correlation among sHER2-ECD levels, HER2-IHC expression, and prognosis was demonstrated. Prospective studies are required to validate the impact of serum and tissue HER2 expression in esophageal SCC prognosis.	esophagus
Laparoscopic creation of a retrosternal route for gastric conduit reconstruction.	BACKGROUND: Retrosternal reconstruction is associated with a lower risk of mediastinitis, gastro-tracheal fistula, and hiatal hernia. Historically, traumatic manual creation of the retrosternal tunnel has been performed using one's fist. We report a novel and atraumatic laparoscopic procedure to create the retrosternal route. METHODS: We have laparoscopically created the retrosternal route in 25 thoracoscopic, mediastinoscopic, or robot-assisted minimally invasive esophagectomies since August 2019. Specifically, a peritoneal incision is started at the dorsal side of the xiphoid process. Through a 12-mm port inserted slightly to the right of and superior to the umbilical camera port, we dissect loose connective tissues from the caudal to the cranial side using behind the sternum and inside the internal thoracic vessels as landmarks. The time required to create the route was calculated. Then, the cumulative sum (CUSUM) method and the simple moving average of five cases were used to evaluate the learning curve of this novel procedure. Operative outcomes were analyzed according to the learning curve results and also compared with 25 cases of postmediastinal reconstruction counterparts. RESULTS: Twenty-five patients were divided into the early group (six patients) and late group (19 patients) based on the peak of the CUSUM chart. The time required for route creation was 28.5 min (median) in the early and 15 min in the late group, indicating a significant difference (P = 0.038). The overall incidence of pleural injury was 20% (5 of 25 patients), with no significant difference between the groups. There was no significant difference in the incidence of perioperative complications. Also, there were no significant differences in perioperative complications or gastric conduit functions 1 year after surgery between the retrosternal and the postmediastinal reconstruction. CONCLUSION: Laparoscopic creation of a retrosternal route for gastric conduit reconstruction is safe and feasible and has a short learning curve.	esophagus
Role of Nutritional Status in the Treatment Outcome for Esophageal Squamous Cell Carcinoma.	Undernourishment is reported to impair treatment response, further leading to poor prognosis for cancer patients. We aimed to investigate the role of nutritional status on the prognosis of squamous cell carcinoma (SCC) of the esophagus, and its correlation with anticancer immune responsiveness. We retrospectively reviewed 340 esophageal-SCC patients who completed curative treatment and received a nutrition evaluation by the Patient-Generated Subjective Global Assessment (PGSGA) score at the beginning and completion of neoadjuvant treatment at our hospital. The correlation between the nutritional status and various clinicopathological parameters and prognosis were examined. In addition, the role of nutritional status in the regulation of the anticancer immune response was also assessed in cancer patients and in a 4-nitroquinoline 1-oxide (4NQO)-induced esophageal tumor model. Our data revealed that malnutrition (patients with a high PGSGA score) was associated with advanced stage and reduced survival rate. Patients in the group with a high PGSGA score were correlated with the higher neutrophil-to-lymphocyte ratio, higher proportion of myeloid-derived-suppressor cells (MDSC) and increased IL-6 level. Furthermore, surgical resection brought the survival benefit to patients in the low PGSGA group, but not for the malnourished patients after neoadjuvant treatment. Using a 4NQO-induced tumor model, we found that nutrition supplementation decreased the rate of invasive tumor formation and attenuated the immune-suppressive microenvironment. In conclusion, malnutrition was associated with poor prognosis in esophageal-SCC patients. Nutritional status evaluated by PGSGA may be useful to guide treatment decisions in clinical practice. Nutritional supplementation is suggested to improve prognosis, and it might be related to augmented anticancer immune response.	esophagus
Accumulation of Uroporphyrin I in Necrotic Tissues of Squamous Cell Carcinoma after Administration of 5-Aminolevulinic Acid.	5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence is widely used for the intraoperative detection of malignant tumors. However, the fluorescence emission profiles of the accompanying necrotic regions of these tumors have yet to be determined. To address this, we performed fluorescence and high-performance liquid chromatography (HPLC) analyses of necrotic tissues of squamous cancer after 5-ALA administration. In resected human lymph nodes of metastatic squamous cell carcinoma, we found a fluorescence peak at approximately 620 nm in necrotic lesions, which was distinct from the PpIX fluorescence peak at 635 nm for viable cancer lesions. Necrotic lesions obtained from a subcutaneous xenograft model of human B88 oral squamous cancer also emitted the characteristic fluorescence peak at 620 nm after light irradiation: the fluorescence intensity ratio (620 nm/635 nm) increased with the energy of the irradiation light. HPLC analysis revealed a high content ratio of uroporphyrin I (UPI)/total porphyrins in the necrotic cores of murine tumors, indicating that UPI is responsible for the 620 nm peak. UPI accumulation in necrotic tissues after 5-ALA administration was possibly due to the failure of the heme biosynthetic pathway. Taken together, fluorescence imaging of UPI after 5-ALA administration may be applicable for the evaluation of tumor necrosis.	esophagus