crossing96/oncoscreening huggingface dataset:
Expression of immune checkpoints in T cells of esophageal cancer patients.	Inhibition of immune checkpoint proteins (checkpoints) has become a promising anti-esophageal cancer strategy. We here tested expressions of immune checkpoints in human esophageal cancers. Our results showed the expressions of many immune checkpoints, including CD28, CD27, CD137L, programmed death 1 (PD-1), T cell immunoglobulin mucin-3 (TIM-3), T cell Ig and ITIM domain (TIGIT), CD160, cytotoxic T lymphocyte antigen 4 (CTLA-4), CD200, CD137 and CD158, were dysregulated in peripheral T cells of esophageal cancer patients. Further, the expressions of PD-1, TIM-3 and TIGIT were upregulated in tumor infiltrating lymphocytes (TILs), which might be associated with TILs exhaustion. Meanwhile, the expressions of PD-1 and TIM-3 on CD4+ T cells were closely associated with clinic pathological features of esophageal cancer patients. These results indicate that co-inhibitory receptors PD-1, TIM-3 and TIGIT may be potential therapeutic oncotargets for esophageal cancer.	esophagus
Genomics of Esophageal Cancer and Biomarkers for Early Detection.	In-depth molecular characterization of esophageal oncogenesis has improved over the recent years. Advancement in molecular biology and bioinformatics has led to better understanding of its genomic landscape. More specifically, analysis of its pathogenesis at the genetic level has uncovered the involvement of a number of tumor suppressor genes, cell cycle regulators, and receptor tyrosine kinases. Due to its poor prognosis, the development of clinically applicable biomarkers for diagnosis, progression, and treatment has been the focus of many research studies concentrating on upper gastrointestinal malignancies. As in other cancers, early detection and subsequent intervention of the preneoplastic condition significantly improves patient outcomes. Currently, clinically approved surveillance practices heavily depend on expensive, invasive, and sampling-error-prone endoscopic procedures. There is, therefore, a great demand to establish clearly reliable biomarkers that could identify those patients at higher risk of neoplastic progression and hence would greatly benefit from further monitoring and/or intervention. This chapter will present the most recent advances in the analysis of the esophageal cancer genome serving as basis for biomarker development.	esophagus
Studying Cancer Evolution in Barrett's Esophagus and Esophageal Adenocarcinoma.	Technological advances in genome sequencing and copy number analysis have allowed researchers to catalog the wide variety of genomic alterations that occur across diverse cancer types. For most cancer types, the lack of high-frequency alterations and the heterogeneity observed both within and between tumors suggest neoplastic progression proceeds through a branched evolutionary pathway as proposed by Nowell in 1976, as opposed to the linear pathway that has dominated medical science for the last century. To understand how cancer evolves over time and space in the body, new study designs are needed that can distinguish between alterations that develop in patients who progress to cancer from to those who don't. Here we present approaches developed in the study of Barrett's esophagus, a premalignant precursor of esophageal adenocarcinoma, and discuss strategies for applying the results from these analyses to address the critical clinical problems of overdiagnosis of benign disease, early detection of life-threatening cancer, and effective risk stratification.	esophagus
Diagnosis by Endoscopy and Advanced Imaging of Barrett's Neoplasia.	Evaluation of patients with Barrett's esophagus (BE) using dye-based chromoendoscopy, optical chromoendoscopy, autofluorescence imaging, or confocal laser endomicroscopy does not significantly increase the number of patients with a diagnosis of early neoplasia compared with high-definition white light endoscopy (HD-WLE) with random biopsy analysis. These newer imaging techniques are not more effective in standard surveillance of patients with BE because the prevalence of early neoplasia is low and HD-WLE with random biopsy analysis detects most cases of neoplasia. The evaluation and treatment of patients with BE and early stage neoplasia should be centralized in tertiary referral centers, where procedures are performed under optimal conditions, by expert endoscopists. Lesions that require resection are almost always detected by HD-WLE, although advanced imaging techniques can detect additional flat lesions. However, these are of limited clinical significance because they are effectively eradicated by ablation therapy. No endoscopic imaging technique can reliably assess submucosal or lymphangio invasion. Endoscopic resection of early stage neoplasia in patients with BE is important for staging and management. Optical chromoendoscopy can also be used to evaluate lesions before endoscopic resection and in follow-up after successful ablation therapy.	esophagus
The Complex, Clonal, and Controversial Nature of Barrett's Esophagus.	Barrett's esophagus (BO) is a preneoplastic condition described as the replacement of the stratified squamous epithelium of the distal esophagus with one that histologically presents as a diverse mixture of metaplastic glands resembling gastric or intestinal-type columnar epithelium. The clonal origins of BO are still unclear. More recently, we have begun to investigate the relationship between the various metaplastic gland phenotypes observed in BO, how they evolve, and the cancer risk they bestow. Studies have revealed that glands along the BO segment are clonal units containing a single stem cell clone that can give rise to all the differentiated epithelial cell types in glands. Clonal lineage tracing analysis has revealed that Barrett's glands are capable of bifurcation and this facilitates clonal expansion and competition. In fact, BO in some patients appears to consist of multiple, independently initiated clones that compete with each other for space and possibly resources. This chapter discusses the concepts of clonal competition and expansion in BO and sets out to query what we know about the role of gland diversity and phenotypic evolution within this complex columnar metaplasia.	esophagus
Proximal Resection Margin in Ivor-Lewis Oesophagectomy for Cancer.	OBJECTIVE: The purpose of this study was to investigate whether a long proximal oesophageal resection margin (PRM) is associated with improved survival after oesophagectomy for cancer and to identify the optimal margin to aim for in this patient group. METHODS: A prospectively maintained database identified 174 patients who underwent Ivor-Lewis oesophagectomy for cancer. Demographic, clinical, and pathological data were collected. X-tile software was used to identify the optimal resection point. Two models were analysed: single point resection with comparison of two groups (short and long), and two resection points with three groups (short, medium, and long) to provide a range. RESULTS: The median PRM was 4.0 cm (interquartile range: 2.5-6.0 cm). After adjustment for significant confounders, multivariable Cox PH analysis demonstrated that the optimal resection margin was 1.7 cm, and in the three-group analysis the optimum PRM was between 1.7 and 3 cm. In the two-group analysis, the long margin had no effect on DFS (p = 0.37), but carried a significantly improved overall survival (hazard ratio [HR] = 0.46, 95 % confidence interval [CI] 0.25-0.87, p = 0.02). In the three-group analysis, the medium and long groups had improved OS compared with the short group (on average 54 %, HR ≥ 0.45, p ≤ 0.04). The 5-year disease-free and overall survival rates were highest in the medium PRM group (48 and 57 % respectively). CONCLUSIONS: Optimal survival following oesophagectomy for cancer is achieved with a PRM > 1.7 cm, but a PRM > 3 cm does not yield a further survival advantage. Thus, the optimal PRM is likely to be between 1.7 and 3 cm.	esophagus
Possible tumor suppressive role of the miR-144/451 cluster in esophageal carcinoma as determined by principal component regression analysis.	MicroRNA (miRNA) clusters are expressed universally across different types of organisms, and an accumulating number of studies have demonstrated that miRNA clusters function more efficiently compared with single miRNAs during the development of certain cancer types. miRNA clusters may have increased stability and reliability over individual miRNAs as diagnostic or therapeutic biomarkers. In the present study, the expression levels of mature miRNAs within the miR-144/451 cluster were examined using stem‑loop reverse transcription‑quantitative polymerase chain reaction in 102 patients pathologically diagnosed with esophageal carcinoma. Bioinformatics tools were used to identify a possible miRNA‑mediated network of the miR‑144/451 cluster. The expression levels of hsa‑miR‑451a, hsa‑miR‑144‑3p and hsa‑miR‑144‑5p in tumor tissues were significantly lower compared with those in adjacent non‑tumor tissues (P<0.05). Pearson correlation analysis demonstrated that the expression levels of individual miR‑144/451 cluster members were correlated with each other, except for the pair of hsa‑miR‑144‑3p and hsa‑miR‑4732‑3p. In particular, hsa‑miR‑144‑5p expression was highly associated with hsa-miR-4732‑5p and hsa-miR-451a expression levels, with correlation coefficients of 0.729 and 0.608, respectively. Furthermore, the low expression levels of hsa‑miR‑144‑3p [odds ratio (OR), 0.85; P<0.05] and hsa-miR-144-5p (OR, 0.84; P<0.05) were determined to be risk factors for esophageal carcinoma development. Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that miRNAs forming the miR‑144/451 cluster may cooperate to regulate the cell cycle. Therefore, the miR‑144/451 cluster may serve an important role in the progression of esophageal carcinoma and may be considered as a biomarker for the detection of esophageal carcinoma at an early stage.	esophagus
Targeted therapies for advanced and metastatic adenocarcinoma of the gastroesophageal junction: is there something new?	Despite improvements in systemic chemotherapy (CT), the prognosis of metastatic adenocarcinoma of the gastroesophageal junction remains poor. Over the years, new targeting agents have become available and were tested, with or without CT, in first or subsequent lines of therapy. The epidermal growth factor receptor family was targeted with monoclonal antibodies (MoAbs) (trastuzumab, cetuximab, panitumumab) and tyrosin kinase inhibitors (TKIs) (lapatinib, erlotinib, gefitinib). Only trastuzumab, in combination with cisplatin and fluoropyrimidines, significantly improved overall survival (OS) in first-line therapy (13.8 vs. 11.1 months). Angiogenesis also was targeted with MoAbs (bevacizumab and ramucirumab); ramucirumab, a vascular endothelial growth factor-receptor 2 antagonist, enhanced OS in two phase III studies in the first (9.6 vs. 7.4 months) and subsequent lines of treatment (5.2 vs. 3.8 months), while the bevacizumab study was negative. TKIs (sunitinib, sorafenib, regorafenib, apatinib) were tested in this setting in phase II studies in the second/third line, only showing modest antitumor activity. The hepatocyte growth factor receptor (MET) was targeted in untreated patients in a phase III trial with MoAb rilotumumab, with or without CT, but the study was stopped because of mortality excess in the rilotumumab arm. Mammalian target of rapamycin (MTOR) pathway inhibition with everolimus was tested in pretreated patients in a placebo-controlled phase III trial who failed to improve OS (5.4 vs. 4.3 months). In conclusion, considering the modest survival gain obtained overall, the high cost of these therapies and the quality of life issue must be primarily considered in treating these patients.	esophagus
Effect of Esophagus Position on Surgical Difficulty and Postoperative Morbidities After Thoracoscopic Esophagectomy.	The objective include thoracoscopic esophagectomy for the deep-seated (left-sided) esophagus has several technical difficulties, which may affects the intraoperative or postoperative outcomes. However, no previous studies have focused on the correlation between the position of the esophagus and short-term outcome after thoracoscopic esophagectomy. Of 470 esophagectomies between April 2005 and April 2015 in Kumamoto University Hospital, 112 patients who underwent thoracoscopic esophagectomy for esophageal cancer were examined. The position of the esophagus was divided into 2 types: deep-seated esophagus or another type based on computed tomographic images in the supine position. In results, the deep-seated esophagus was associated with a longer operation time in the thorax and high incidence of severe morbidity of Clavien-Dindo classification ≥IIIb, pneumonia, and any pulmonary morbidity. The deep-seated esophagus was also an independent risk factor for severe morbidity (hazard ratio [HR] = 5.37, 95% CI: 1.307-22.03; P = 0.020), pneumonia (HR = 9.23, 95% CI: 2.150-39.60; P = 0.003), and any pulmonary morbidity (HR = 10.3, 95% CI: 2.714-38.78; P < 0.001). In conclusion, the position of the esophagus had a strong influence on the difficulty of thoracoscopic esophagectomy and the incidence of postoperative morbidities. Surgeons would be well advised to keep a careful watch perioperatively for patients with a deep-seated esophagus.	esophagus
Plasma microRNA profiles: identification of miR-23a as a novel biomarker for chemoresistance in esophageal squamous cell carcinoma.	BACKGROUND: This study aims to explore novel microRNAs in plasma for predicting chemoresistance in preoperative chemotherapy of patients with esophageal squamous cell carcinoma (ESCC) using a microRNA array-based approach. RESULTS: (1) Four candidate microRNAs (miR-223, 103a, 23b and 23a), which were highly expressed in the pretreatment plasma of patients with a low histopathologic response, were selected. (2) In a large-scale validation analysis by quantitative RT-PCR, plasma levels of miR-223, miR-23b and miR-23a were significantly higher in patients with a low histopathologic response than in those with a high histopathologic response (p = 0.0345, p = 0.0125 and p = 0.0114). (3) Of all candidate microRNAs, miR-23a expression of pretreatment ESCC tumor tissues was significantly higher in ESCC patients with a low histopathologic response than in those with a high histopathologic response (p = 0.0278). (4) After overexpressing each candidate in ESCC cells, miR-23a induced significant chemoresistance to both 5-fluorouracil and cisplatin, and miR-223 to cisplatin in vitro. (5) A high level of plasma miR-23a, which tended to correlate with lymphatic invasion (p = 0.0808) and deep depth of invasion (p = 0.0658), was an independent risk factor for chemoresistance in ESCC (p = 0.0222; odds ratio: 12.4; range 1.46-105). MATERIALS AND METHODS: We used the Toray® 3D-Gene microRNA array-based approach to compare plasma microRNA levels between patients with a high or a low histopathologic response to chemotherapy. All patients underwent a preoperative chemotherapy regimen with cisplatin plus 5-fluorouracil. CONCLUSIONS: Plasma miR-23a might be a useful biomarker for predicting chemoresistance in ESCC patients.	esophagus
Angiotensin II type I receptor (AT1R) is an independent prognosticator of esophageal squamous cell carcinoma and promotes cells proliferation via mTOR activation.	BACKGROUND: The aim of this study was to investigate the effects of the angiotensin II/ angiotensin II type I receptor (AT1R) and angiotensin II type II receptor (AT2R) signaling pathway in esophageal squamous cell carcinoma (ESCC). METHODS: Immunohistochemistry was performed to evaluate the expression levels of AT1R and AT2R in tissues from 152 surgically resected ESCC patients, and those expression levels were then correlated with treatment outcomes. The angiotensin II/AT1R/AT2R signaling pathway and its biological effects in the context of ESCC were investigated in vitro and in vivo. RESULTS: In human samples, AT1R overexpression was univariately associated with inferior overall survival and remained multivariately independent (hazard ratio=1.812). In vitro, angiotensin II stimulated the growth of ESCC cells in a dose-dependent manner. Treatment with irbesartan or AT1R-RNAi knockdown but not treatment with PD123319 significantly decreased the level of angiotensin II-induced ESCC cell proliferation. Angiotensin II also caused mTOR activation in a dose-dependent manner, and everolimus or mTOR-RNAi knockdown significantly suppressed the level of angiotensin II-induced ESCC cell proliferation. Furthermore, AT1R-RNAi knockdown suppressed the activation of mTOR. Clinically, AT1R expression was also correlated with phosphorylated mTOR expression. In a xenograft model, local angiotensin II injection enhanced tumor growth, and this effect could be decreased by treatment with irbesartan or everolimus. In a 4-NQO-induced-ESCC murine model, irbesartan significantly decreased the incidence of esophageal tumor. CONCLUSIONS: These findings suggest that AT1R overexpression is an independent adverse prognosticator for patients with ESCC and that angiotensin II/AT1R signaling stimulates ESCC growth, in part through mTOR activation.	esophagus
Rare Presentation of Gastroesophageal Carcinoma with Rectal Metastasis: A Case Report.	BACKGROUND Gastroesophageal cancers, previously considered rare, are rapidly increasing worldwide. We present here a unique case of gastroesophageal carcinoma with metastasis to the rectum. CASE REPORT A 60-year-old female patient presented with constipation, bloating, and weight loss of 4-month duration. She had undergone sleeve gastrectomy 6 years before. Endoscopies performed revealed a friable-looking mucosa in the lower esophagus and a polypoid rectal mass. Histopathological examination from both the esophageal and rectal lesions revealed poorly differentiated adenocarcinoma cells. Immunohistochemistry stain from both specimens was positive for CK7 supporting the gastric site primary with metastasis to the rectum. Further evaluation also revealed metastasis to bone and malignant pleural effusion. Chemotherapy with palliative intent was initiated. CONCLUSIONS Colorectal metastasis is commonly seen from cancers of the breast, stomach, melanoma, kidney, prostate, and ovaries. However, colorectal metastasis from gastroesophageal cancer has never been reported in the medical literature. Diagnosis relies on histopathologic examination and immunohistochemical staining of the tumor. Treatment depends on the tumor stage. Tumors with widespread metastatic disease are candidates for palliative chemotherapy.	esophagus
Somatic mutations in plasma cell-free DNA are diagnostic markers for esophageal squamous cell carcinoma recurrence.	OBJECTIVES: Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignancies owing to the high frequency of tumor recurrence. The identification of markers for early ESCC diagnosis and prediction of recurrence is expected to improve the long-term prognosis. Therefore, we searched for associations between tumor recurrence and cell-free DNA (cfDNA) mutations in blood plasma, which contains genetic markers for various cancer types. EXPERIMENTAL DESIGN: Genomic DNA from tumors and cfDNA from plasma were obtained from 13 patients undergoing treatment for newly diagnosed ESCC. Next-generation sequencing of cfDNA in plasma was performed to identify mutations in 53 cancer-related genes, in which recurrent mutations were previously detected in ESCC. cfDNA mutational profiles were compared before and after tumor resection in four patients. Furthermore, somatic mutations in serial plasma samples were monitored after treatment in four patients. RESULTS: We identified multiple concordant somatic mutations in cfDNA and primary tumor samples from 10 patients (83.3%) and in cfDNA and metastatic tumor samples from one patient (100%). Furthermore, the allele frequency of the concordant mutations in cfDNA changed concomitantly with tumor burden and increased approximately 6 months earlier than the detection of tumor recurrences by imaging tests in two patients. Conventional biomarkers, such as SCC and p53-Ab, did not reflect tumor recurrences. CONCLUSIONS: The present multigene panel, which enabled the diagnosis of tumor recurrence with greater accuracy than did using standard tumor markers or imaging methods, is expected to greatly facilitate standard, postoperative follow-up monitoring in ESCC.	esophagus
Transhiatal Esophagectomy for Esophageal Cancer.	Survival for esophageal cancer has improved over the past four decades, probably as a result of a combination of more accurate staging, improved surgical outcomes, advances in adjuvant and neoadjuvant therapies, and the increasing implementation of multimodality treatment. Surgical resection still remains the mainstay in the treatment of localized esophageal adenocarcinoma. Multiple techniques have been described for esophagectomy, which are based on either a transthoracic or transhiatal approach. Despite proponents of each technique touting potential advantages such as superior oncologic resection with more extensive transthoracic lymphadenectomy compared to the relatively limited morbidity and mortality with a transhiatal resection, the superiority of one technique over another is not clear and may be relegated to a topic of historical significance in the era of minimally invasive surgery. With the increased acceptance of neoadjuvant multimodality therapy, both approaches have been shown to have acceptable outcomes. And in the hands of experienced surgeons, both techniques can provide excellent short-term results. Moreover, surgeon and hospital volume have shown to be strongly associated with improved operative morbidity and oncologic outcomes, which may supersede the type of approach selected for an individual patient.	esophagus
Evaluation of preoperative staging for esophageal squamous cell carcinoma.	Esophageal squamous cell carcinoma (ESCC) is known for its rapid progression and poor outcomes. China has the highest incidence and mortality in the world. Diagnoses made at early stages and accurate staging are associated with better outcomes, all of which can play a significant role in the selection of treatment protocols. ESCC is staged according to the widely accepted TNM system. Common imaging modalities used in staging ESCC before treatment include endoscopy, computed tomography (CT), positron emission tomography (PET) and magnetic resonance imaging (MRI). Endoscopic ultrasound is useful for staging tumor depth and nodal status. Narrow band imaging is valuable for early stage disease assessment. CT and PET provide additional valuable information regarding node and metastasis staging. The ability of MRI to delineate ESCC is continuously being improved and adds information regarding locoregional status to routine examinations.	esophagus
The Role of the Microbiome in Gastrointestinal Cancer.	Humans are host to complex microbial communities previously termed normal flora and largely overlooked. However, resident microbes contribute to both health and disease. Investigators are beginning to define microbes that contribute to the development of gastrointestinal malignancies and the mechanisms by which this occurs. Resident microbes can induce inflammation, leading to cell proliferation and altered stem cell dynamics, which can lead to alterations in DNA integrity and immune regulation and promote carcinogenesis. Studies in human patients and rodent models of cancer have identified alterations in the microbiota of the stomach, esophagus, and colon that increase the risk for malignancy.	esophagus