Malignant Gastrointestinal Tumor Research Articles

Study of newly diagnosed Gastroenterology tumors and associated risk factors at Tishreen University Hospital in Lattakia – Syria

Objective: The study was conducted in order to determine the epidemiological characteristics of referred patients at Tishreen University Hospital in Lattakia and who have been diagnosed with one of the types of malignant Gastrointestinal tumors and study the distribution of risk factors in these patients. Patients and Methods: An Observational Descriptive study (Cross- Sectional) conducted for the period from January 2020 to January 2021 at Tishreen University Hospital in Lattakia- Syria (in Gastrointerolog Department). The variables analyzed were age, gender, tumor location and risk factors Results: The research sample included 223 patients (127 males and 96 females). Esophageal tumors are relatively rare and most of them are of the squamous cell carcinoma type (72.8%). Stomach tumors are the second most common tumor with a percentage of (23.8%), and adenocarcinoma constituted 89% of the cases. Colon and rectal cancer represented the largest percentage (35%) of gastrointestinal tumors, and half of these tumors were in the rectum. Pancreatic cancer ranked third with 11.2% of cases. Tumors of the small intestine and gallbladder and hepatocellular carcinoma are relatively rare. Our most frequently seen risk factors were smoking in most tumors, positivity for H. pylori in 70% of gastric adenocarcinoma patients, and family history and inflammatory bowel disease in Colon tumor patients. Conclusion: Although the incidence of some gastrointestinal cancers has decreased, these cancers continue to pose major challenges to public health, especially colorectal tumors.

TCF12 activates MAGT1 expression to regulate the malignant progression of pancreatic carcinoma cells.

As a highly malignant gastrointestinal tumor, pancreatic carcinoma (PC) has poor prognosis due to its low early diagnosis rate, advanced tumor resection and chemotherapy resistance. Magnesium transporter 1 (MAGT1) is a magnesium ion transporter located on the cell membrane, which shows promotive effects on biological behaviors of multiple tumor cells. The aim of the present study was to investigate the role of MAGT1 in the progression of PC and its potential molecular mechanism. Based on the Gene Expression Profiling Interactive Analysis website, MAGT1 was highly expressed in tissues from patients with PC and was associated with poor prognosis. In functional experiments, MAGT1 was highly expressed in PC cell lines. The Cell Counting Kit-8, gap closure and Transwell assays, and western blot analysis, were used to investigate the effects of MAGT1 overexpression or knockdown on the biological behaviors of PC cells. It was found that MAGT1 promoted the proliferation, migration and invasion of PC cells in vitro. According to the Encyclopedia of RNA Interactomes website, transcription factor 12 (TCF12) mRNA expression level was positively correlated with MAGT1 expression level in the tissues from patients with PC. Positive targeting regulation of MAGT1 by TCF12 was also confirmed using a dual-luciferase gene reporter assay and chromatin immunoprecipitation. In addition, knockdown of TCF12 expression inhibited the proliferation and migration of PC cells, but overexpression of MAGT1 expression partly reversed this. These results suggested that TCF12 could promote the proliferation, migration and invasion of PC cells by activating MAGT1 expression, which was associated with poor prognosis. These findings suggest that MAGT1 could be a promising biomarker for the occurrence, progression and prognosis of PC.

Mesenchymal tumors and tumor-like lesions of the gastrointestinal tract: an overview

Mesenchymal tumors and tumor-like lesions of the gastrointestinal (GI) tract are uncommon. They vary from reactive tumefactive lesions and benign neoplasms to highly aggressive sarcomas. Among them, GI stromal tumors (GISTs) are most common, followed, with less frequency, by smooth muscle and neurogenic tumors. The major challenge resides in correctly identifying GISTs and providing acomprehensive report (including risk assessment and genotyping) that represents the basis for an optimized surgical-oncological treatment and/or adjuvant therapy. On the other hand, the challenge of benign lesions is to find agood name (well understandable and reproducible diagnostic term) that helps avoid diagnostic ambiguity and prognostic uncertainty so that overprognostication and overtreatment can be prevented. Moreover, several recently described genetically defined benign and malignant entities need be correctly diagnosed due to their special "targeted" therapeutic options and to further characterize their clinicopathological and biological properties in the future. These recent entities include aggressive epithelioid inflammatory myofibroblastic sarcoma (ALK-RANBP2-driven), malignant gastrointestinal neuroectodermal tumor (EWSR1-ATF1/CREB-related), NTRK-rearranged neoplasms, and, most recently, colorectal NUTM1-rearranged sarcomas. This review highlights the major clinicopathological features of gastrointestinal mesenchymal lesions in light of recent developments.

LncRNA FOXP4-AS1 Promotes the Progression of Esophageal Squamous Cell Carcinoma by Interacting With MLL2/H3K4me3 to Upregulate FOXP4.

Malignant tumors are a grave threat to human health. Esophageal squamous cell carcinoma (ESCC) is a common gastrointestinal malignant tumor. China has a high incidence of ESCC, and its morbidity and mortality are higher than the global average. Increasingly, studies have shown that long noncoding RNAs (lncRNAs) play a vital function in the occurrence and development of tumors. Although the biological function of FOXP4-AS1 has been demonstrated in various tumors, the potential molecular mechanism of FOXP4-AS1 in ESCC is still poorly understood. The expression of FOXP4 and FOXP4-AS1 was detected in ESCC by quantitative real-time PCR (qRT–PCR) or SP immunohistochemistry (IHC). shRNA was used to silence gene expression. Apoptosis, cell cycle, MTS, colony formation, invasion and migration assays were employed to explore the biological functions of FOXP4 and FOXP4-AS1. The potential molecular mechanism of FOXP4-AS1 in ESCC was determined by dual-luciferase reporter, RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP). Here, we demonstrated that FOXP4-AS1 was significantly increased in ESCC tissues and cell lines, associated with lymph node metastasis and TNM staging. Cell function experiments showed that FOXP4-AS1 promoted the proliferation, invasion and migration ability of ESCC cells. The expression of FOXP4-AS1 and FOXP4 in ESCC tissues was positively correlated. Further research found that FOXP4-AS1, upregulated in ESCC, promotes FOXP4 expression by enriching MLL2 and H3K4me3 in the FOXP4 promoter through a “molecular scaffold”. Moreover, FOXP4, a transcription factor of β-catenin, promotes the transcription of β-catenin and ultimately leads to the malignant progression of ESCC. Finally, FOXP4-AS1 may be a new therapeutic target for ESCC.

Efficacy and Safety of Lanreotide Autogel in the Treatment of Clinical Symptoms Associated With Inoperable Malignant Intestinal Obstruction: A Prospective Phase II Study

PurposeInoperable malignant intestinal obstruction (IMIO) is a severe complication in patients with cancer, usually gastrointestinal or gynecologic in origin. For patients with IMIO, there is a need to relieve symptoms and limit nasogastric tube (NGT) use. Previous studies have suggested the efficacy of somatostatin analogues in relieving obstruction-related symptoms, such as nausea, vomiting, and pain. The purpose of this study was to assess the efficacy of lanreotide autogel 120 mg (LAN 120 mg) in the management of symptoms resulting from IMIO in patients with advanced cancer. MethodsThis single-arm, multicenter study enrolled 52 patients mostly with advanced gastrointestinal or ovarian malignant tumors (35 patients with NGT and 17 patients without NGT). Patients received 1 deep subcutaneous injection of LAN 120 mg. Evaluations were performed on days 7, 14, and 28. The primary end point was the percentage of responding patients before or at day 7. Response was defined as ≤2 vomiting episodes per day (for patients without NGT at baseline) or no vomiting recurrence (after NGT removal) during at least 3 consecutive days at any time point between treatment and day 7. Responders at day 28 were offered a second LAN 120 mg injection and followed up until day 56. FindingsThe proportion of responders in the intention-to-treat population was 24 of 52 (46.2%), which was significantly greater than the reference proportion of 30% (P = 0.0055). Patients without NGT had a higher response (88.2%) than patients with NGT (25.7%) and had a steady trend for clinical improvement that led to sustainable responses. Median time to response was 9 days for the overall population, 3 days for patients without NGT, and 14 days for patients with NGT (P < 0.0001). ImplicationsOur study is the first to use long-acting LAN 120 mg in patients with IMIO and suggests an effect in controlling clinical symptoms in patients with and without NGT at baseline. The safety profile of LAN 120 mg was similar to that reported in other indications. ClinicalTrials.gov identifier: NCT02275338.

Clinical Features and Prognostic Factors of Acute Ischemic Stroke Related to Malignant Gastrointestinal Tumor.

Objectives: To analyze the clinical and imaging features of acute ischemic stroke (AIS) related to gastrointestinal malignant tumor, and to explore the prognostic factors.Methods: Clinical data of consecutive patients with gastrointestinal malignant tumor complicated with AIS admitted to the Department of Neurology and Oncology in Lanzhou University Second Hospital from April 2015 to April 2019 were retrospectively analyzed. Patients were divided into good prognosis (mRS 0–2) and poor prognosis (mRS > 2) based on a 90-day mRS score after discharge. The multivariate logistic regression model was used to analyze the prognostic factors.Results: A total of 68 patients were enrolled with an average age of 61.78 ± 6.65 years, including 49 men (72.06%). There were 18 patients in the good prognosis group and 50 patients in the poor prognosis group. The univariate analysis showed that Hcy, D-dimer, thrombin–antithrombin complex (TAT), and three territory sign in magnetic resonance imaging (MRI) were the risk factors for poor prognosis. Multivariate analysis showed that increased D-dimer (OR 4.497, 95% CI 1.014–19.938) and TAT levels (OR 4.294, 95% CI 1.654–11.149) were independent risk factors for the prognosis in such patients.Conclusion: Image of patients with gastrointestinal malignant tumor-related AIS is characterized by three territory sign (multiple lesions in different vascular supply areas). Increased TAT and D-dimer levels are independent prognostic risk factors. TAT is more sensitive to predict prognosis than D-dimer.

Malignant Gastrointestinal Neuroectodermal Tumor: a case report and a review of the literature

Abstract Introduction/Objective Malignant gastrointestinal neuroectodermal tumor (GNET) is a rare soft tissue tumor arising in the wall of the gastrointestinal tract. The GNET was first described as an osteoclast rich tumor of the gastrointestinal tract with features resembling clear cell sarcoma, with only few cases reported in the literature. Methods/Case Report We report a case of a 71-year-old man with a past medical history of hypertension, hyperlipidemia, and benign prostatic hyperplasia presented with complaints of dyspnea, dizziness, fatigue, black stools, and a recent syncopal episode. Laboratory testing revealed anemia (HB 5.4 g/dL). Esophagogastroduodenoscopy demonstrated a submucosal gastric mass. An abdominal CT scan confirmed a 7.8 cm mass along the gastric cardia and fundus. Results (if a Case Study enter NA) Biopsy rendered a gastrointestinal neuroectodermal tumor (GNET). Microscopically, the tumor cells were spindle with eosinophilic cytoplasm and arranged in fascicules. They were positive for CD56, CD99, and Fli-1, synaptophysin, and negative for chromogranin, TTF-1, SMA, desmin, CD34, EMA, pan-cytokeratin, and lymphoid markers. Two months later, further imaging confirmed metastasis to the liver and spleen. GNETs typically arise within the muscularis propria of the gastrointestinal tract and often extend into the submucosa and subserosa. Conclusion The most important differential of GNET is the clear cell sarcoma of the gastrointestinal tract (CCS-GI). Both share similar morphological as well as molecular features and show S100 positivity; however, the lack of melanocytic differentiation in GNET distinguishes it from CCS-GI. Both typically show rearrangements of the EWSR1 gene, with t(12;22) (q13;q12) EWSR1-ATF1 or t(2;22)(q34;q12) EWSR1-CREB1 fusions. Pathologists should be aware of GNET diagnostic entity due to its aggressive behavior and high rate of recurrence and mortality even after complete resection.

Proliferating cell nuclear antigen clamp associated factor, a potential proto-oncogene with increased expression in malignant gastrointestinal tumors.

Gastrointestinal (GI) cancers, including malignancies in the gastrointestinal tract and accessory organs of digestion, represent the leading cause of death worldwide due to the poor prognosis of most GI cancers. An investigation into the potential molecular targets of prediction, diagnosis, prognosis, and therapy in GI cancers is urgently required. Proliferating cell nuclear antigen (PCNA) clamp associated factor (PCLAF), which plays an essential role in cell proliferation, apoptosis, and cell cycle regulation by binding to PCNA, is a potential molecular target of GI cancers as it contributes to a series of malignant properties, including tumorigenesis, epithelial-mesenchymal transition, migration, and invasion. Furthermore, PCLAF is an underlying plasma prediction target in colorectal cancer and liver cancer. In addition to GI cancers, PCLAF is also involved in other types of cancers and autoimmune diseases. Several pivotal pathways, including the Rb/E2F pathway, NF-κB pathway, and p53-p21 cascade, are implicated in PCLAF-mediated diseases. PCLAF also contributes to some diseases through dysregulation of the p53 pathway, WNT signal pathway, MEK/ERK pathway, and PI3K/AKT/mTOR signal cascade. This review mainly describes in detail the role of PCLAF in physiological status and GI cancers. The signaling pathways involved in PCLAF are also summarized. Suppression of the interaction of PCLAF/PCNA or the expression of PCLAF might be potential biological therapeutic strategies for GI cancers.

Influencing Factors of Gastrointestinal Function Recovery after Gastrointestinal Malignant Tumor.

Gastric cancer is a malignant tumor with a high incidence in the world, and the incidence rate only increases every year. Because of the loss of mental property caused by surgery and postoperative recovery treatment, it has become a difficult problem for many families to solve. Exploring the factors affecting the recovery of gastrointestinal function after surgery to accelerate the recovery has become one of the important research topics of current medical experts and scholars. The purpose of this article is to explore the factors affecting the recovery of gastrointestinal function after gastrointestinal malignancies. In this paper, firstly through experimental investigation, the fasting time and operation method of patients undergoing gastrointestinal malignant tumor surgery are used as variables to conduct a controlled experiment, and the first defecation time, exhaust time, and bowel sound recovery of the experimental subjects after surgery are recorded. Changes in time and other indicators are compared to verify whether they affect the recovery of gastrointestinal function. Experimental data showed that the recovery time of bowel sounds was 29.10 ± 11.09 h in patients with fasting time less than or equal to 2 days after operation, the time of first exhaustion was 28.75 ± 27.80 h, and the time of first defecation was 54.70 ± 39.40 h. The recovery time of bowel sounds in patients with fasting time longer than 2 days was 40.47 ± 9.40 h, the first exhaust time was 71.40 ± 17.54 h, and the first defecation time was 98.30 ± 28.16 h. Therefore, resuming diet as soon as possible after operation is beneficial to the recovery of gastrointestinal function in patients with gastrointestinal malignancies.

Effects of dexmedetomidine on glucose-related hormones and lactate in non-diabetic patients under general anesthesia: a randomized controlled trial

The aim of this study was to explore the effects of dexmedetomidine on glucose-related hormones and lactate levels in non-diabetic patients undergoing malignant gastrointestinal tumor radical resection. Groups D<inf>1</inf> and D<inf>2</inf> received dexmedetomidine loading dose 1 µg/kg and maintenance dose 0.25 and 0.5 µg/kg/h, respectively. Group C received saline solution. Glucose, lactate, insulin, glucagon, cortisol, epinephrine, norepinephrine and dopamine levels were measured before dexmedetomidine infusion (T<inf>1</inf>), 1 h after surgery beginning (T<inf>2</inf>), at surgery ending (T<inf>3</inf>), and 1 h after transfer to the postanesthesia care unit (T<inf>4</inf>). Compared with group C, glucose levels increased in group D<inf>2</inf> at T<inf>2</inf> and reduced in groups D<inf>1</inf> and D<inf>2</inf> at T<inf>4</inf>. Lactate levels reduced in groups D<inf>1</inf> and D<inf>2</inf> at T<inf>4</inf>. A positive correlation between glucose and lactate levels was found in all groups. Compared with group C, insulin level reduced in group D<inf>2</inf> at T<inf>2</inf>; glucagon levels reduced in groups D<inf>1</inf> and D<inf>2</inf> at T<inf>4</inf>; cortisol levels reduced in group D<inf>1</inf> at T<inf>4</inf> and in group D<inf>2</inf> at T<inf>3</inf> and T<inf>4</inf>; epinephrine and norepinephrine levels reduced in group D<inf>1</inf> at T<inf>4</inf> and in group D<inf>2</inf> at T<inf>2</inf> and T<inf>4</inf>; and dopamine level reduced in group D<inf>2</inf> at T<inf>4</inf>. Dexmedetomidine loading dose 1 µg/kg and maintenance dose 0.25 µg/kg/h produces a stable insulin level and significant postoperative decreases in glucagon, cortisol, epinephrine and norepinephrine secretion with stable maintenance of intraoperative and postoperative blood glucose levels and decreased postoperative lactate levels in non-diabetic patients under general anesthesia.

Assessment the Characteristic Features of Colorectal Cancer among Patients Attending Tikrit Teaching Hospital from 2009-2013

Background: Colorectal cancer is a frequent malignant gastrointestinal tumor. The studies in the "Iraqi Cancer Registry" from eighties revealed that the incidence of this cancer in Iraq duplicated up to (2.6%), but six to thirteen percent in the developed countries and higher in industrial countries about seventeen to fifty percent. It is the second cause of death in the western countries; colorectal cancer is ranked, after lung and prostate cancer in male, while it is after breast and lung cancer in females. The disease is frequent among elderly but (6-8%) of patients were 40 years and younger. Colorectal cancers are of favourable prognosis if early diagnosis and treatment provided. This study aims to assess the frequency of colorectal cancer in Tikrit city, to highlight the recently noted increase in frequency among young. Patients and Methods: The current study is cross-sectional study done in January 2014 when all recorded cases of colorectal cancer 2009-2013 involved in the study. It enrolled (172) patients with colorectal cancer chosen as a convenience sample. Data collected from hospital records (records between the 1st of January 2009 to the 31st of December 2013) in statistic unit in Tikrit Teaching Hospital. The demographic information, distribution, presentation, histopathological types and staging have been described. The staging system used in this study was the modified Dukes' staging system (6) . Results: Of the (172) patients involved in this study, 94 patients (54.7%) were males and 78(45.3%) were females with a male: female ratio of (1.2:1), mean age was (51.4) years and peak age of occurrence was (60-69) years age group. The main presenting symptom was abdominal pain (42.4%). The most common site of the tumor was the rectum (35%) and (97.8%) of cancers were adenocarcinomas of which (66.7%) were moderately differentiated. (38%) of cases were at Duke‘s stage B when diagnosed. Conclusion: The study showed an increase colon cancer frequency during the year 2013 compared with previous years, with a notable increase among young adults, high percentage of them presented with advanced and aggressive disease. Recommendations: Increase awareness of population about the importance of colorectal cancer screening to discover a disease at early stage which can be treated completely.

Malignant gastrointestinal neuroectodermal tumor: Cytologic, histologic, immunohistochemical, and molecular pitfalls

Malignant gastrointestinal neuroectodermal tumor (GNET) is a rare malignant primary gastrointestinal mesenchymal tumor which can be diagnosed via fine-needle aspiration (FNA) cytology. In the context of FNA, the diagnosis requires a cell block and the use of significant resources including immunohistochemical stains and molecular testing. The differential diagnosis of GNET includes clear cell sarcoma (CCS), gastrointestinal stromal tumor (GIST), gastric schwannoma, metastatic melanoma, malignant perivascular epithelioid cell tumor (PEComa) and granular cell tumor, among others. Here we describe a case which was initially diagnosed as malignant granular cell tumor by FNA which was later revised to GNET following the finding of an EWSR1-ATF1 fusion gene rearrangement.

Novel Hemorrhagic Risk Score in Elderly Patients with Coronary Artery Disease and Gastrointestinal Malignant Tumor Comorbidity: A 10-year Clinical Inpatient Data Analysis from 2 Medical Centers

Abstract Objective: Older patients with comorbidity, such as coronary heart disease (CHD) and malignant gastrointestinal tumors, are at a high risk of bleeding events. However, risk prediction models based on risk factor assessment remain unclear. This study aimed to establish an individualized bleeding risk assessment system based on the analysis of 10-year inpatient clinical big data. Methods: Total clinical data of 56,819 patients with CHD and 25,988 patients with malignant digestive tract tumors (admitted from January 2008 to December 2017) were retrospectively collected at the First and Second Medical Centers of Chinese People's Liberation Army General Hospital. Among them, 1307 patients with CHD and malignant digestive tract tumors were screened as the derivation cohort. The dependent variable was the occurrence of major clinical bleeding events. Baseline statistics and hypothesis tests of differences were performed for independent variables according to the occurrence of bleeding. Decision Tree, eXtreme Gradient Boosting (XGBoost), logistic regression, and random forest models were used for comparison. The accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC-ROC) were applied as the criteria for evaluating and verifying model performance. To evaluate this developed model, another cohort comprising 454 patients (admitted from January 2018 to December 2019) was prospectively enrolled as the validation cohort based on the same inclusion and exclusion criteria. Results: Among the 64 variables with &lt;50% missing values, the recursive feature elimination method with a random forest model was used to screen the selected variables. The highest accuracy was obtained following the selection of 10 scalars, and the final model was constructed accordingly. XGBoost demonstrated the best performance comprehensively. The AUC-ROC of this model was 0.981, with an accuracy, sensitivity, and specificity of 0.939, 0.950, and 0.927, respectively. In the validation cohort, the AUC-ROC, accuracy, sensitivity, and specificity of the XGBoost model were 0.702, 0.718, 0.636, and 0.725, respectively. The rate of major bleeding events has a positive correlation with the bleeding risk score quintiles. To allow for convenient clinical application, a smartphone application was developed for easy access and calculation (http://fir.master-wx.com/sghr). Conclusion: We successfully established a risk model and score for predicting bleeding events in older patients with comorbidity, such as CHD and gastrointestinal cancer.

Abstract 2184: Gene characteristics of Chinese patients with small bowel cancer

Abstract Background: Small bowel cancer is a rare malignancy which account for only 1-3% of all malignant gastrointestinal tumors. Herein, we aim to provide an overview of gene characteristics of Chinese patients with small bowel cancer based on the location of the tumor in the small bowel. Methods: Tumor samples of 324 Chinese patients with small bowel cancer were consecutively collected in China from February 2018 to May 2020, among them, 289 patients with cancer located in duodenum (group 1), 35 patients with cancer located in the other region of small bowel (group 2). Next generation sequencing (NGS) was performed to detect gene mutation, microsatellite instability (MSI), and tumor mutational burden (TMB) measured by a 733 gene panel by 3D Medicines, a laboratory accredited by College of American Pathologists (CAP) and Clinical Laboratory Improvement Amendments (CLIA). Results: NGS results revealed that the main mutated genes were different between two groups, in detail, the top ten gene mutation in group 1 were TP53 (51.4%,18/35), KRAS (45.7%, 16/35), APC (34.3%, 12/35), POLE (20.0%,7/35), PIK3CA/POLD1/MSH2 (17.1%,6/35), mTOR/PRSS1/LPR1B/BRCA1/SMAD4 (14.3%,5/35). While top ten gene mutation in group 2 were TP53 (66.4%,192/289), KRAS (49.8%, 144/289), ERCC1 (38.8%, 112/289), UGT1A1 (31.5%, 91/289), APC (29.4%, 85/289), BRCA1 (28.7%,83/289), AKT2 (27.3%, 79/289).In addition, TMB level and percentage of MSI-H were also compared between the two groups. 12 patients were available for TMB analysis in group 1, 59 for group 2, the average TMB level in two groups were 23.84 mutants/Mb and 7.8 mutants/Mb, respectively. 50%(6/12) and 11.8%(7/59) were under 10 mutants/Mb in two groups. What's more, the percentage of MSI-H in two groups were 16.7% (5/30) and 3.2% (8/243). Conclusion: Patients with cancer located in duodenum patients with cancer located in the other region of small bowel displayed obvious difference in gene landscape, this imply that these patients should be treated differently. Citation Format: Quan Zhao, Hushan Zhang, Zhuyun Lei, Jianing Sheng, Dun Xiong. Gene characteristics of Chinese patients with small bowel cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2184.

A Ferroptosis-Related Gene Signature Identified as a Novel Prognostic Biomarker for Colon Cancer.

BackgroundColon cancer (CC) is a common gastrointestinal malignant tumor with high heterogeneity in clinical behavior and response to treatment, making individualized survival prediction challenging. Ferroptosis is a newly discovered iron-dependent cell death that plays a critical role in cancer biology. Therefore, identifying a prognostic biomarker with ferroptosis-related genes provides a new strategy to guide precise clinical decision-making in CC patients.MethodsAlteration in the expression profile of ferroptosis-related genes was initially screened in GSE39582 dataset involving 585 CC patients. Univariate Cox regression analysis and LASSO-penalized Cox regression analysis were combined to further identify a novel ferroptosis-related gene signature for overall survival prediction. The prognostic performance of the signature was validated in the GSE17536 dataset by Kaplan-Meier survival curve and time-dependent ROC curve analyses. Functional annotation of the signature was explored by integrating GO and KEGG enrichment analysis, GSEA analysis and ssGSEA analysis. Furthermore, an outcome risk nomogram was constructed considering both the gene signature and the clinicopathological features.ResultsThe prognostic signature biomarker composed of 9 ferroptosis-related genes accurately discriminated high-risk and low-risk patients with CC in both the training and validation datasets. The signature was tightly linked to clinicopathological features and possessed powerful predictive ability for distinct clinical subgroups. Furthermore, the risk score was confirmed to be an independent prognostic factor for CC patients by multivariate Cox regression analysis (p < 0.05). Functional annotation analyses showed that the prognostic signature was closely correlated with pivotal cancer hallmarks, particularly cell cycle, transcriptional regulation, and immune-related functions. Moreover, a nomogram with the signature was also built to quantify outcome risk for each patient.ConclusionThe novel ferroptosis-related gene signature biomarker can be utilized for predicting individualized prognosis, optimizing survival risk assessment and facilitating personalized management of CC patients.

Mesenchymal tumours of the gastrointestinal tract.

SummaryMesenchymal tumours represent a heterogenous group of neoplasms encopassing benign, intermediate malignancy, and malignant entities. Sarcomas account for approximately 1% of human malignancies. In consideration of their rarity as well as of intrinsic complexity, diagnostic accuracy represents a major challenge. Traditionally, mesenchymal tumours are regarded as lesions the occurrence of which is mostly limited to somatic soft tissues. However, the occurrence of soft tissue tumours at visceral sites represent a well recognized event, and the GI-tract ranks among the most frequently involved visceral location. There exist entities such as gastrointestinal stromal tumours (GIST) and malignant gastointestinal neuroectodermal tumors that exhibit exquisite tropism for the GI-tract. This review will focus also on other relevant clinico-pathologic entities in which occurrence at visceral location is not at all negligible.

Knockdown of NOLC1 Inhibits PI3K-AKT Pathway to Improve the Poor Prognosis of Esophageal Carcinoma.

Objective Esophageal carcinoma (ESCA) is a common malignant gastrointestinal tumor. The abnormal expression of NOLC1 is involved in the tumorigenesis of various human tumors, whereas the function and mechanism of NOLC1 in ESCA remain unclear. In this study, we explored the relationship between NOLC1 and poor prognosis of ESCA, and its role and mechanism in the occurrence of ESCA. Methods The NOLC1 expression in ESCA tissues and cell lines was determined by qRT-PCR, immunohistochemistry, or western blot. The Kaplan–Meier method was conducted to estimate the overall survival. Cox regression analysis was carried out to examine the association between patient characteristics and prognosis. A recombined lentiviral vector containing NOLC1 was applied for transfecting ESCA cells (Eca109 and TE-13) and established a stable cell line with low NOLC1 expression or high NOLC1 expression, in the absence or presence of PI3K inhibitor (LY294002) treatment. Cell proliferation, apoptosis rate, invasion ability, migration ability, and PI3K/AKT pathway were detected by CCK8 assay, flow cytometry, Transwell assay, wound-healing assay, and western blot. Results NOLC1 overexpression was observed in ESCA tissues and ESCA cell lines (EC9706, Eca109, TE-13, Kyse170, T.TN) compared with adjacent normal tissues and normal esophageal cell line HEEC. NOLC1 overexpression was markedly associated with bigger tumor size, lymph node metastasis, and advanced TNM stage. Patients with NOLC1 overexpression have shorter overall survival than that of those with low NOLC1 expression. NOLC1 overexpression was considered to be an independent poor prognostic factor affecting overall survival. NOLC1 knockdown inhibited proliferation, migration, invasion, and cyclin B1 expression and promoted the apoptosis and cleaved-caspase-3 expression of Eca109 and TE-13 cells. NOLC1 overexpression accelerated proliferation, migration, invasion, and cyclin B1 expression and inhibited the apoptosis and cleaved-caspase-3 expression of ESCA cells via activating PI3K/AKT pathway. Rescue experiments showed that PI3K inhibitor (LY294002) could reverse the phenomenon caused by NOLC1 overexpression. Conclusion NOLC1 may be a marker for poor prognosis. It can participate in the occurrence and development of ESCA via the PI3K/AKT pathway.

Integrated analysis of potential pathways by which aloe-emodin induces the apoptosis of colon cancer cells

BackgroundColon cancer is a malignant gastrointestinal tumour with high incidence, mortality and metastasis rates worldwide. Aloe-emodin is a monomer compound derived from hydroxyanthraquinone. Aloe-emodin produces a wide range of antitumour effects and is produced by rhubarb, aloe and other herbs. However, the mechanism by which aloe-emodin influences colon cancer is still unclear. We hope these findings will lead to the development of a new therapeutic strategy for the treatment of colon cancer in the clinic.MethodsWe identified the overlapping targets of aloe-emodin and colon cancer and performed protein–protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. In addition, we selected apoptosis pathways for experimental verification with cell viability, cell proliferation, caspase-3 activity, DAPI staining, cell cycle and western blotting analyses to evaluate the apoptotic effect of aloe-emodin on colon cancer cells.ResultsThe MTT assay and cell colony formation assay showed that aloe-emodin inhibited cell proliferation. DAPI staining confirmed that aloe-emodin induced apoptosis. Aloe-emodin upregulated the protein level of Bax and decreased the expression of Bcl-2, which activates caspase-3 and caspase-9. Furthermore, the protein expression level of cytochrome C increased in a time-dependent manner in the cytoplasm but decreased in a time-dependent manner in the mitochondria.ConclusionThese results indicate that aloe-emodin may induce the apoptosis of human colon cancer cells through mitochondria-related pathways.

Screening of immunosuppressive cells from colorectal adenocarcinoma and identification of prognostic markers.

Background: Colorectal cancer (CRC) is the most common type of gastrointestinal malignant tumour. Colorectal adenocarcinoma (COAD) – the most common type of CRC – is particularly dangerous. The role of the immune system in the development of tumour-associated inflammation and cancer has received increasing attention recently.Methods: In the present study, we compiled the expression profiles of 262 patients with complete follow-up data from The Cancer Genome Atlas (TCGA) database as an experimental group and selected 65 samples from the Gene Expression Omnibus (GEO) dataset (of which 46 samples were with M0) as a verification group. First, we screened the immune T helper 17 (Th17) cells related to the prognosis of COAD. Subsequently, we identified Th17 cells-related hub genes by utilising Weighted Gene Co-expression Network Analysis (WGCNA) and Least Absolute Shrinkage and Selector Operation (LASSO) regression analysis. Six genes associated with the prognosis in patients with COAD were identified, including: KRT23, ULBP2, ASRGL1, SERPINA1, SCIN, and SLC28A2. We constructed a clinical prediction model and analysed its predictive power.Results: The identified hub genes are involved in developing many diseases and closely linked to digestive disorders. Our results suggested that the hub genes could influence the prognosis of COAD by regulating Th17 cells’ infiltration.Conclusions: These newly discovered hub genes contribute to clarifying the mechanisms of COAD development and metastasis. Given that they promote COAD development, they may become new therapeutic targets and biomarkers of COAD.

Up-regulation of miR-204 inhibits proliferation, invasion and apoptosis of gallbladder cancer cells by targeting Notch2.

Gallbladder carcinoma (GC) is an extremely malignant gastrointestinal tumor, but relevant mechanisms are still under investigation. MicroRNA (miR) is differentially expressed in a variety of tumors. Here we explored miR-204 in patients with GC and related mechanisms. A GSE104165 chip was downloaded from the gene expression omnibus (GEO) for analysis. The qRT-PCR assay was used for quantifying miR-204 and Notch2 in the serum and tissues of the patients, and the patients were followed up for 3 years to analyze independent factors of prognosis. The CCK8, transwell, and flow cytometry assays were applied for analyzing proliferation, invasion, as well as apoptosis of cells, and the dual luciferase reporter (DLR) assay was adopted for determining the association of miR-204 with Notch2. MiR-204 was low in patients with GC, and it might serve as a diagnostic indicator for GC. In addition, patients with low e MiR-204 usually faced high rates of III+IV stage, distant metastasis, and low differentiation, and also showed a poor prognosis. DLR assay verified the targeted binding of miR-204 to Notch2 mRNA.