crossing96/oncoscreening huggingface dataset:
Nuclear PKM2 expression predicts poor prognosis in patients with esophageal squamous cell carcinoma.	Esophageal squamous cell carcinoma (ESCC) is one of the most common tumors worldwide, with a high malignant degree and poor prognosis. The present study aims to investigate the relationship between pyruvate kinase M2 (PKM2) expression and the prognosis of patients with ESCC. The expression of PKM2 in 86 cases of esophageal carcinoma tissues was tested using immunohistochemistry. The relationship between PKM2 expression and clinical pathological parameters, and their effects on the prognosis of patients with ESCC were analyzed. The expression levels of PKM2 in both cytoplasm and nucleus of ESCC tissues were significantly higher than those in paracancerous tissues (P=6.73×10(-9) and 4.32×10(-6), respectively). The Kaplan-Meier analysis showed that nuclear PKM2 expression was closely related to the survival of patients with ESCC (P=0.005). Patients with high PKM2 expression in the nucleus had significantly shorter survival times than those with low PKM2 expression in the nucleus (hazard ratio for death, 2.358; 95% confidence interval, 1.156-4.812; P=0.018). No other significant difference was found between PMK2 expression and clinico-pathological features of ESCC patients (all P>0.05). In conclusion, high PKM2 expression in the nucleus is essential in the pathogenic process of ESCC and may be used to predict the prognosis of patients with ESCC.	esophagus
Multidisciplinary modalities achieve encouraging long-term survival in resectable limited-disease esophageal small cell carcinoma.	BACKGROUND: The management of limited-disease esophageal small cell carcinoma is not well defined, and the role of surgery is still controversial. We aim to determine the optimal treatment strategy in limited-disease of esophageal small cell carcinoma. METHODS AND FINDINGS: We conducted a retrospective review of 141 patients with limited-disease esophageal small cell carcinoma from 3 institutions in China who underwent treatment between July 1994 and September 2008, July 1994 and July 2011, and June 2004 and December 2010, respectively. The survival rate was calculated by the Kaplan-Meier method, and the log-rank test was used to assess the survival differences between the groups. Cox proportional hazards model were used to further determine the independent factors impacting overall survival. The median survival time was 16.1 months for the entire cohort of patients, with a 5-year survival rate of 6.7%. The median survival times for surgery alone, surgery combined with chemotherapy, surgery combined with radiotherapy, surgery combined with chemotherapy and radiotherapy, chemotherapy plus radiotherapy, and chemotherapy alone were 18.0 months, 15.0 months, 23.0 months, 25.0 months, 17.1 months, and 6.1 months, respectively; the corresponding 5-year survival rates were 0%, 15.4%, 0%, 38.9%, 0%, and 0%, respectively. For the 105 patients who underwent R0 resection, the median disease-free survival time was 12.0 months, with a 95% confidence interval of 9.5 months to 14.5 months. The multivariate Cox regression analysis demonstrated that advanced pathological staging (p = 0.003), and pure esophageal small cell carcinoma (p = 0.035) were independent factors decreasing overall survival. CONCLUSIONS: Our data suggested that multidisciplinary modalities achieved encouraging long-term survival in patients with resectable limited-disease of esophageal small cell carcinoma.	esophagus
Esophageal squamous cell carcinoma and gastric cardia adenocarcinoma shared susceptibility locus in PLCE1: a meta-analysis.	BACKGROUND AND OBJECTIVE: Two recent genome-wide association studies have identified a shared susceptibility variation PLCE1 rs2274223 for esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinomas (GCA). Subsequent case-control studies have reported this association in other populations. However, the findings were controversial and the effect remains undetermined. Our aim is to provide a precise quantification of the association between PLCE1 rs2274223 variation and the risk of ESCC and GCA. METHODS: Studies were identified by a literature search in MEDLINE and EMBASE databases. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association in allele, dominant, recessive, homozygous, and heterozygous models. RESULTS: Ten articles were identified, including 22156 ESCC cases and 28803 controls, 5197 GCA cases and 17613 controls. Overall, PLCE1 rs2274223 G allele (G vs. A: OR=1.26, 95% CI: 1.15-1.39 for ESCC; OR=1.51, 95% CI: 1.35-1.69 for GCA) and its carrier (GG +AG vs. AA: OR = 1.23; 95% CI =1.02-1.49 for ESCC; OR =1.62; 95% CI =1.15-2.29 for GCA) were significantly associated with the risk of ESCC and GCA. In stratified analysis by ethnicity, significant association of PLCE1 rs2274223 G allele and the risk of ESCC (OR=1.33, 95% CI 1.21-1.45) and GCA (OR =1.56, 95% CI: 1.47-1.64) was observed in Chinese population. CONCLUSIONS: Our meta-analysis results indicated that PLCE1 rs2274223 G allele significantly contributed to the risk of ESCC and GCA, especially in Chinese population.	esophagus
Genetic variants in epidermal growth factor receptor pathway genes and risk of esophageal squamous cell carcinoma and gastric cancer in a Chinese population.	The epidermal growth factor receptor (EGFR) signaling pathway regulates cell proliferation, differentiation, and survival, and is frequently dysregulated in esophageal and gastric cancers. Few studies have comprehensively examined the association between germline genetic variants in the EGFR pathway and risk of esophageal and gastric cancers. Based on a genome-wide association study in a Han Chinese population, we examined 3443 SNPs in 127 genes in the EGFR pathway for 1942 esophageal squamous cell carcinomas (ESCCs), 1758 gastric cancers (GCs), and 2111 controls. SNP-level analyses were conducted using logistic regression models. We applied the resampling-based adaptive rank truncated product approach to determine the gene- and pathway-level associations. The EGFR pathway was significantly associated with GC risk (P = 2.16×10(-3)). Gene-level analyses found 10 genes to be associated with GC, including FYN, MAPK8, MAP2K4, GNAI3, MAP2K1, TLN1, PRLR, PLCG2, RPS6KB2, and PIK3R3 (P<0.05). For ESCC, we did not observe a significant pathway-level association (P = 0.72), but gene-level analyses suggested associations between GNAI3, CHRNE, PAK4, WASL, and ITCH, and ESCC (P<0.05). Our data suggest an association between specific genes in the EGFR signaling pathway and risk of GC and ESCC. Further studies are warranted to validate these associations and to investigate underlying mechanisms.	esophagus
Sirtuin-3 (SIRT3) expression is associated with overall survival in esophageal cancer.	Sirtuin-3 (SIRT3) was immunostained in 94 samples of esophageal cancer tissues and semiquantified using the HSCORE method to evaluate the predictive value of SIRT3 expression levels on esophageal cancer outcome. The relationship between SIRT3 expression and the 5-year survival rate of postoperational esophageal cancer patients was assessed with the Kaplan-Meier method. High expression of SIRT3 is associated with a shorter survival time in esophageal cancer patients, as shown by the log-rank test (P = .007), and the level of SIRT3 expression was identified as an independent predictor for esophageal cancer outcome using Cox proportional hazards model analysis (relative risk, 2.061; 95% confidence interval, 1.050-4.046; P = .036). SIRT3 expression was associated with esophageal cancer outcome. The analysis of SIRT3 levels can help in the identification of patient subgroups that are at high risk for poor disease outcomes.	esophagus
Gastric cancer staging with radiologic imaging modalities and UICC staging system.	There are two major stage classification systems for gastric cancer: the tumor-node-metastasis (TNM) stages by the International Union against Cancer (UICC) and the Japanese Classification of Gastric Carcinoma by the Japanese Gastric Cancer Association (JGCA). Preoperative stage classification using either of these systems is essential for deciding on the treatment strategy in the era of various multimodal therapeutic options. Evolution of multidetector computerized tomography with isotropic volumetric imaging and various 3D images has increased the accuracy of T and N staging in patients with gastric cancer, although detection of peritoneal deposits and nodal metastasis in the absence of lymphadenopathy remain problematic with the imaging tools currently available. The TNM and JGCA classifications have undergone revisions independent of each other, and the discrepancies were not helpful when international comparisons and cooperation were needed. More recently, the JGCA and TNM classifications were merged to have identical T and N categories, in addition to the more straightforward M categories that indicate the presence of distant metastasis. The result of these efforts is that researchers in Japan and the rest of the world are now looking at a similar disease when they discuss cancer that belongs to the same stage. A nomogram that incorporates other established prognostic determinants in addition to the TNM component may be a future direction for a more sophisticated means of predicting outcome. The increasing incidence of junctional (esophagogastric junction) cancer in the Far East has spurred researchers from this region to adequately stage the disease and to consider suitable treatment modalities for this disease entity, whereas Western researchers are more inclined to treat this disease as esophageal cancer. This could be an area for future international debate. For the next more accurate staging, we suggest the collaboration between Eastern and Western high-volume centers in gastric cancer because the inconsistency of surgical approaches, especially with respect to nodal resection, remains a barrier to mutual understanding.	esophagus
Regional variations in esophageal cancer rates by census region in the United States, 1999-2008.	BACKGROUND: Assessment of cancer incidence trends within the U.S. have mostly relied upon Surveillance, Epidemiology, and End Results (SEER) data, with implicit inference that such is representative of the general population. However, many cancer policy decisions are based at a more granular level. To help inform such, analyses of regional cancer incidence data are needed. Leveraging the unique resource of National Program of Cancer Registries (NPCR)-SEER, we assessed whether regional rates and trends of esophageal cancer significantly deviated from national estimates. METHODS: From NPCR-SEER, we extracted cancer case counts and populations for whites aged 45-84 years by calendar year, histology, sex, and census region for the period 1999-2008. We calculated age-standardized incidence rates (ASRs), annual percent changes (APCs), and male-to-female incidence rate ratios (IRRs). RESULTS: This analysis included 65,823 esophageal adenocarcinomas and 27,094 esophageal squamous cell carcinomas diagnosed during 778 million person-years. We observed significant geographic variability in incidence rates and trends, especially for esophageal adenocarcinomas in males: ASRs were highest in the Northeast (17.7 per 100,000) and Midwest (18.1). Both were significantly higher than the national estimate (16.0). In addition, the Northeast APC was 62% higher than the national estimate (3.19% vs. 1.97%). Lastly, IRRs remained fairly constant across calendar time, despite changes in incidence rates. CONCLUSION: Significant regional variations in esophageal cancer incidence trends exist in the U.S. Stable IRRs may indicate the predominant factors affecting incidence rates are similar in men and women.	esophagus
Triangulating stapling technique for esophagogastrostomy after minimally invasive esophagectomy.	BACKGROUND: The triangulating stapling technique is one of the reconstruction methods used that provides favorable surgical outcomes in several areas of the digestive tract. However, the results in the cervical esophagogastric anastomosis are not well documented. METHODS: Using a prospectively maintained comprehensive database, we reviewed the surgical results of 160 consecutive patients who underwent minimally invasive esophagectomy followed by cervical triangulating stapling esophagogastrostomy during 2 periods from May 2002 to May 2012 so as to determine the efficacy of the triangulating stapling technique using 2 different types of stapling devices. RESULTS: The rates of anastomotic leakage and stricture in this series were low (1% and 15%, respectively). The rate of anastomotic stricture was significantly reduced when a linear stapler with a cutting knife was used (9%). A logistic regression analysis showed a reduction of anastomotic stricture to be significantly associated with the use of only a linear stapler with a cutting knife. CONCLUSION: Cervical esophagogastric anastomosis by the triangulating stapling technique is safe and feasible. We consider a linear stapling device equipped with a cutting knife to be more suitable for performing the triangulating stapling technique.	esophagus
Robustness of intratumour ¹⁸F-FDG PET uptake heterogeneity quantification for therapy response prediction in oesophageal carcinoma.	PURPOSE: Intratumour uptake heterogeneity in PET quantified in terms of textural features for response to therapy has been investigated in several studies, including assessment of their robustness for reconstruction and physiological reproducibility. However, there has been no thorough assessment of the potential impact of preprocessing steps on the resulting quantification and its predictive value. The goal of this work was to assess the robustness of PET heterogeneity in textural features for delineation of functional volumes and partial volume correction (PVC). METHODS: This retrospective analysis included 50 patients with oesophageal cancer. PVC of each PET image was performed. Tumour volumes were determined using fixed and adaptive thresholding, and the fuzzy locally adaptive Bayesian algorithm, and heterogeneity was quantified using local and regional textural features. Differences in the absolute values of the image-derived parameters considered were assessed using Bland-Altman analysis. The impact on their predictive value for the identification of patient nonresponders was assessed by comparing areas under the receiver operating characteristic curves. RESULTS: Heterogeneity parameters were more dependent on delineation than on PVC. The parameters most sensitive to delineation and PVC were regional ones (intensity variability and size zone variability), whereas local parameters such as entropy and homogeneity were the most robust. Despite the large differences in absolute values obtained from different delineation methods or after PVC, these differences did not necessarily translate into a significant impact on their predictive value. CONCLUSION: Parameters such as entropy, homogeneity, dissimilarity (for local heterogeneity characterization) and zone percentage (for regional characterization) should be preferred. This selection is based on a demonstrated high differentiation power in terms of predicting response, as well as a significant robustness with respect to the delineation method used and the partial volume effects.	esophagus
Adenocarcinomas of the esophagogastric junction: experiences at a single institution in China.	BACKGROUND: The incidence of adenocarcinoma of the esophagogastric junction is increasing. This study aims to evaluate the clinicopathological features of Chinese patients with adenocarcinoma of the esophagogastric junction and to define prognostic factors. METHODS: We retrospectively reviewed a database of 382 consecutive patients with adenocarcinoma of the esophagogastric junction at the First Affiliated Hospital of Xi'an Jiaotong University from January 2005 to March 2010. All patients were classified according to the Siewert's classification and staged according to the latest edition of the American Joint Committee on Cancer categories. RESULTS: Six of the 382 patients had type I adenocarcinoma, 220 had type II, and 156 had type III. There was no significant difference in the overall survival of different Siewert subtypes. According to the multivariate analysis, pathological lymph node stage, age, and the existence of lymphovascular invasion were the independent factors of prognosis of adenocarcinoma of the esophagogastric junction following surgery. CONCLUSIONS: On the data, the distribution of the three types of tumor was found to be different from that reported in Western countries. Lymph node metastasis, lymphovascular invasion, and age were significant and independent factors for poor prognosis after R0 resection for adenocarcinoma of the esophagogastric junction.	esophagus
Significance of GSTP1 for predicting the prognosis and chemotherapeutic efficacy in esophageal squamous cell carcinoma.	Glutathione S-transferases (GSTs) have been reported to be activated in several types of cancers, including esophageal squamous cell carcinoma (ESCC). The aim of the present study was to investigate whether GSTP1 protein expression is a useful predictor of the clinical outcome or drug resistance in ESCC. Immunohistochemistry was conducted with 75 ESCC resected specimens using a monoclonal antibody against GSTP1. The patients were divided into two groups according to the degree of GSTP1 staining, and the relationship between the GSTP1 level and the clinicopathological features was examined. Seventy-five patients were divided into low (grade 1, n=36) and high (grade 2, n=39) GSTP1 expression groups. The overall survival was significantly worse in the grade 2 patients than in the grade 1 patients (5‑year survival rate, 78.5 vs. 51.2%; p=0.027). Cox proportional hazard analysis revealed that macroscopic type 3 or 4 disease (p=0.001), lymph node metastasis (p=0.010), and high GSTP1 expression (p=0.029) were independent predictors of a poor prognosis. With regard to the subgroup analysis among the 31 patients undergoing adjuvant chemotherapy, the grade 2 patients had a worse prognosis than did the grade 1 patients (5‑year survival rate, 45.0 vs. 81.8%; p=0.081). This tendency was not observed in the subgroup without adjuvant chemotherapy (5‑year survival rate, 51.7 vs. 59.9%; p=0.979). In conclusion, the GSTP1 expression is a good predictor of prognosis, and it may be closely related to the chemotherapeutic efficacy of 5-FU plus cisplatin in ESCC patients.	esophagus
Circulating miR-200c levels significantly predict response to chemotherapy and prognosis of patients undergoing neoadjuvant chemotherapy for esophageal cancer.	BACKGROUND: There is increasing evidence that microRNA expression in cancer tissue is useful for predicting the prognosis of patients with cancer. However, the relationship between the levels of circulating microRNAs and response to chemotherapy and prognosis remains unclear in esophageal cancer. METHODS: We measured the serum levels of miR-21, miR-145, miR-200c, and let-7c by quantitative RT-PCR in 64 patients with esophageal cancer who underwent neoadjuvant chemotherapy. RESULTS: The serum levels of miR-21, miR-145, miR-200c, and let-7c in esophageal cancer patients were significantly higher than those in healthy volunteers. High expression of miR-200c correlated significantly with poor response to chemotherapy (p = 0.0211). There was no significant relationship between chemosensitivity and the levels of miR-21, miR-145, and let-7c. High expression of miR-200c was associated with shortened progression-free survival (p = 0.0076), but there was no significant relationship between prognosis and the expression of miR-21, miR-145, and let-7c. Multivariate analysis identified miR-200c expression as the most valuable prognostic factor for patients with esophageal cancer who receive neoadjuvant chemotherapy. CONCLUSIONS: The serum level of miR-200c can be useful for predicting the response to chemotherapy and the prognosis of patients with esophageal cancer who receive neoadjuvant chemotherapy.	esophagus
A dual mTORC1 and mTORC2 inhibitor shows antitumor activity in esophageal squamous cell carcinoma cells and sensitizes them to cisplatin.	The mammalian target of rapamycin (mTOR) signaling pathway is critical for the growth and proliferation of various malignant tumors, including esophageal squamous cell carcinoma (ESCC). Therefore, targeting of mTOR protein is a promising strategy for therapy in this disease. In the present study, we examined the antitumor effects of a specific mTOR kinase inhibitor, PP242, which blocks both mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) pathways, in two ESCC cell lines: Eca-109 and TE-1. We showed that PP242, but not rapamycin, attenuated the activities of both mTORC1 and mTORC2 signaling in ESCC. PP242 inhibited 4E-binding protein-1 phosphorylation and abrogated mTORC1-dependent PI3K/Akt feedback activation. Significantly, PP242 effectively suppressed ESCC cell proliferation, induced apoptosis, and arrested the cell cycle. Furthermore, PP242 promoted cisplatin-induced apoptosis and enhanced the antitumor efficacy of cisplatin in ESCC cells, which was likely to be associated with inhibition of Akt activity. Our results show that simultaneous targeting of both mTORC1 and mTORC2 pathways leads to effective antitumor actions in ESCC, and strongly suggest that dual mTORC1/2 inhibitors should be developed as potential agents for the treatment of ESCC.	esophagus
Association of p53 and MDM2 polymorphisms with risk of human papillomavirus (HPV)-related esophageal squamous cell carcinoma (ESCC).	PURPOSE: Though polymorphisms of the tumor suppressor gene p53 have been extensively investigated in numerous tumors, particularly tumors associated with human papillomavirus (HPV) infection. However, the results remain controversial. Our previous study showed that HPV serostatus is not an independent risk factor for esophageal squamous cell carcinoma (ESCC) in nonsmokers and nondrinkers. Given the roles of p53 and HPV E6 as well as MDM2 oncoproteins in p53 degradation, we validated the association of p53 and MDM2 polymorphisms with ESCC risk stratified by HPV16 sero-status. METHODS: Single nucleotide polymorphisms of p53 Arg72Pro (rs1042522) and MDM2 (rs937283) in 307 ESCC patients and 311 healthy controls were genotyped. The presence or absence of HPV16 in serum was measured by enzyme-linked immunosorbent assay. Multivariable logistic regression analysis was used to evaluate the possible associations of p53 and MDM2 polymorphisms with ESCC risk stratified by HPV16 sero-status. RESULTS: Patients carrying p53 Arg/Arg or Arg/Pro had a higher risk of esophageal SCC (P<0.001, Odds ratio [OR] 4.98, 95% confidential interval [CI] 3.46-7.17), however, not found in MDM2 rs937283. The risk of esophageal SCC increased significantly among patients carrying p53 Arg/Arg, or Arg/Pro and HPV16-seropositivity (P<0.001, OR 9.33, 95% CI 5.44-16.0), but not for MDM2 rs937283. The risk of esophageal SCC was further elevated among patients carrying Arg/Arg or Arg/Pro and HPV16-seropositivity who were smokers (P<0.001, OR 27.05, 95% CI 11.06-66.16) or drinkers (P<0.001, OR 13.20, 95% CI 5.74-30.38). CONCLUSION: HPV16 seropositivity synergized with p53 Arg/Arg or Arg/Pro and increased ESCC risk, especially in smokers or drinkers.	esophagus