scholarly journals Integrated analysis of long non-coding RNAs and mRNAs associated with malignant transformation of gastrointestinal stromal tumors

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Xiaonan Yin ◽  
Yuan Yin ◽  
Lei Dai ◽  
Chaoyong Shen ◽  
Na Chen ◽  
...  
Keyword(s):  
Malignant Transformation ◽  
Gastrointestinal Stromal Tumors ◽  
Underlying Mechanism ◽  
Mitotic Rate ◽  
Integrated Analysis ◽  
Hippo Signaling ◽  
Stromal Tumors ◽  
Tight Association ◽  
Worse Prognosis

AbstractMalignant transformation of gastrointestinal stromal tumors (GISTs) is correlated with poor prognosis; however, the underlying biological mechanism is not well understood. In the present study, low-risk (LR) GISTs, GISTs categorized as high-risk based on tumor size (HBS), and on mitotic rate (HBM) were collected for RNA sequencing. Candidate hub lncRNAs were selected by Oncomine analysis. Expression of a selected hub lncRNA, DNM3OS, and its correlation with patients’ prognosis were analyzed using FISH staining, followed with the determination of function and underlying mechanism. Our results revealed a series of key pathways and hub lncRNAs involved in the malignant transformation of GISTs. Oncomine analysis revealed a tight association between clinical signatures and DNM3OS and suggested that DNM3OS is a hub lncRNA that is involved in the Hippo signaling pathway. In addition, DNM3OS was upregulated in HBS, HBM, and HBS/M GIST and correlated with worse prognosis in patients with GISTs. In addition, DNM3OS promoted GIST cell proliferation and mitosis by regulating the expression of GLUT4 and CD36. Collectively, these results improve our understanding of the malignant transformation of GISTs and unveil a series of hub lncRNAs in GISTs.

Integrated Analysis of Long Non-Coding RNAs and mRNAs Associated With Malignant Transformation of Gastrointestinal Stromal Tumors

2020 ◽  
Author(s):  
Xiaonan Yin ◽  
Yuan Yin ◽  
Lei Dai ◽  
Chaoyong Shen ◽  
Na Chen ◽  
...  
Keyword(s):  
Malignant Transformation ◽  
Gastrointestinal Stromal Tumors ◽  
Underlying Mechanism ◽  
Mitotic Rate ◽  
Integrated Analysis ◽  
Hippo Signaling ◽  
Stromal Tumors ◽  
Tight Association ◽  
Worse Prognosis

Abstract Background: Malignant transformation of gastrointestinal stromal tumors (GISTs) is correlated with poor prognosis; however, the underlying biological mechanism is not well understood. Methods: In the present study, low-risk (LR) GISTs, GISTs categorized as high-risk based on tumor size (HBS), and on mitotic rate (HBM) were collected for RNA sequencing. Candidate hub lncRNAs were selected by Oncomine analysis. Expression of a selected hub lncRNA, DNM3OS, and its correlation with patients’ prognosis were analyzed using FISH staining, followed with the determination of function and underlying mechanism. Results: Our results revealed a series of key pathways and hub lncRNAs involved in the malignant transformation of GISTs. Oncomine analysis revealed a tight association between clinical signatures and DNM3OS and suggested that DNM3OS is a hub lncRNA that is involved in the Hippo signaling pathway. In addition, DNM3OS was upregulated in HBS, HBM, and HBS/M GIST and correlated with worse prognosis in patients with GISTs. In addition, DNM3OS promoted GIST cell proliferation and mitosis by regulating the expression of GLUT4 and CD36. Conclusions: These results improve our understanding of the malignant transformation of GISTs and unveil a series of hub lncRNAs in GISTs.

scholarly journals Immunohistochemical features of gastrointestinal stromal tumors and their role for differential diagnosis and prognosis

2021 ◽  
pp. 10-16
Author(s):  
Yana Miroshnichenko
Keyword(s):  
Differential Diagnosis ◽  
Tumor Cells ◽  
Gastrointestinal Stromal Tumors ◽  
Spindle Cell ◽  
Prognostic Markers ◽  
Mitotic Rate ◽  
Mesenchymal Tumors ◽  
Ki 67 ◽  
Stromal Tumors ◽  
Strong Expression

The aim. To clarify all most important immunohistochemical features of gastrointestinal stromal tumors with different histological patterns and analyze the role of expression of Ki-67, MMP-9, VEGF and p16ink4A as a predictive markers of tumor progression. Materials and methods. The study is based on analysis of 100 primary GISTs for description of their morphological features and 36 GISTs taken from this 100 for study of prognostic markers. Results. All spindle cell GISTs have shown diffuse expression of CD117 in tumor cells. The levels of CD117 expression varied from strong expression (3+) until mild expression (1+). Strong expression were seen in 75,8 % of spindle cell GISTs. Epithelioid GISTs demonstrated heterognous moderate or mild expression of CD117. All primary epithelioid GISTs from patients that had relapse of tumor in period from 1 till 3 years demonstrated focal mild expression of CD 117 in tumor cells. Expression of DOG-1 were seen in all 100 cases of GISTs, that were included in our study. The strong expression of DOG-1 (3+) were seen in all 45 GISTs that had low mitotic rate (≤5 mitoses per 50HPF) and not associated with their histological pattern. GISTs with high mitotic rate demonstrated heterogeneous expression of DOG-1 in tumors: moderate expression (2+) with patchy areas of strong expression (3+). Expression of CD56 was not found in spindle cell GISTs, but single tumor cells of epithelioid GISTs that had high mitotic rate demonstrated expression of this marker. The average expression of p16ink4A were higher in tumors that gave relapses compared with tumors without relapses (50,3 % versus 5,7 % respectively, U-test=16.5; p≤0,01).The average expression of MMP-9 also were significantly higher in GISTs that gave relapses: 63,2 % compared with 13,4 % in GISTs without relapse (U-test=16; p≤0 ,01).The strong VEGF expression was found in 66,7 % of GISTs that had relapses and only in 8,3 % of GISTs without relapses. 50 % of GISTs without relapses was negative for VEGF. Finally, the average expression of Ki-67 were 13,4 % in GISTs with relapses and 8,7 % in GISTs without them (U-test=16; p≤0,01). Conclusion. We highly recommend using DOG-1 for epithelioid GISTs. Additionally in epithelioid GISTs can be used CD56 that can give focal positive reaction in some tumour cells. The following minimal panel of markers for differential diagnosis of spindled GISTs from other mesenchymal tumors of gastrointestinal tract is proposed: CD117, DOG-1 and SMA, where the first too markers will demonstrated the moderate or strong diffuse expression and SMA can be occasionally positive in some tumor cells. p16ink4A, ki-67, VEGF and MMP-9 can be used as additional prognostic markers in GISTs.

A Review of Sleeve Gastrectomy Specimen Histopathology

2016 ◽  
Vol 82 (11) ◽  
pp. 1101-1104 ◽  
Author(s):  
Luke A. Kinsinger ◽  
James C. Garber ◽  
Oliver Whipple
Keyword(s):  
Sleeve Gastrectomy ◽  
Intestinal Metaplasia ◽  
Retrospective Review ◽  
Gastrointestinal Stromal Tumors ◽  
Mitotic Rate ◽  
Single Institution ◽  
Stromal Tumors ◽  
Increased Risk ◽  
Risk Of Malignancy ◽  
Lymphoid Aggregates

With the increasing popularity of sleeve gastrectomy, many stomach specimens are being evaluated. Understanding the significance and treatment for unexpected pathology is important. This study examines the incidence of relevant histopathology of sleeve gastrectomy specimens. It evaluates previous data for each histopathology and provides recommendations for treatment. In this study, a retrospective review was performed for 241 patients who underwent sleeve gastrectomy from 2009 to 2014 at a single institution. Of the specimens, 122 had no significant histopathology, 91 had gastritis, 13 had lymphoid aggregates, 5 had hyperplasia, 3 had intestinal metaplasia, 3 had gastrointestinal stromal tumors (GISTs), and 3 had gastric polyps. Of the GISTs all had a low mitotic rate and the size of the tumor ranged from 1.5 to 4.5 cm. The findings of metaplasia may be a marker for increased risk of malignancy and may require additional surveillance. The findings of GIST may warrant interval imaging to survey for recurrence, though the likelihood of recurrence for the tumors in this study is less than 2 per cent based on previous studies.

Characteristics of gastrointestinal stromal tumors incidentally discovered during abdominal surgery.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 835-835
Author(s):  
Meera Garg ◽  
Kyle Joseph Hitscherich ◽  
Joseph J. Bennett
Keyword(s):  
Small Bowel ◽  
Abdominal Surgery ◽  
Gastrointestinal Stromal Tumors ◽  
Elective Surgery ◽  
Surgical Oncology ◽  
Mitotic Rate ◽  
Study Patient ◽  
Cancer Center ◽  
Stromal Tumors ◽  
Almost All

835 Background: Gastrointestinal Stromal Tumors (GISTs) are rare sarcomas with 5000 new cases each year. Despite their low incidence, surgeons should be familiar with this pathology since GISTs can be encountered incidentally during abdominal surgery. Methods: A retrospective series was conducted by querying pathology and operative reports from a community cancer center between 2005 and 2019 for all GIST diagnoses. Patients identified to have incidental GISTs discovered intra-operatively while undergoing surgery for another diagnosis were the focus of this study. Patient and tumor characteristics were evaluated. Results: A total of 195 patients had a diagnosis of a resected GIST during our study period. Of these 195, 48 patients were incidentally discovered to have a GIST excised during another index operation. The average age of these patients was 62 years old, 27 were female and 21 male. The primary location of these incidental GISTs in descending frequency was stomach (62.5%, n = 30), small bowel (31.3%, n = 15), colon (4.2%, n = 2) and esophagus (2.1%, n = 1). The average GIST size for the cohort was 1.7cm, with stomach, small bowel, colon and esophagus measured at 1.8cm, 1.7cm, 0.65cm and 0.30cm, respectively. Mitotic rate was < 5 mitosis/50 HPF in 96% of patients. Incidental GISTs were identified during the following surgery: colon (n = 14), bariatric (n = 13), non-bariatric gastric (n = 10), hernia (n = 4), pancreatic (n = 3), esophageal (n = 2) and other (n = 2). Most incidental GISTs were discovered during elective surgery (81.3%, n = 39) compared to emergency surgery (18.8%, n = 9), and for benign disease (n = 33) compared to malignant (n = 15). Conclusions: Approximately one quarter of all GISTs resected at our community cancer center in 15 years were discovered incidentally, and during a wide variety of abdominal surgeries for both benign and malignant disease. Almost all these GISTs were < 2cm, benign, and should be cured with the incidental resection. Abdominal surgeons should be aware of unexpectedly finding small GISTs and should not be apprehensive about resecting since they have indolent characteristics. Larger lesions should trigger expert surgical oncology consultation.

scholarly journals Robust linear regression model of Ki-67 for mitotic rate in gastrointestinal stromal tumors

2014 ◽  
Vol 7 (3) ◽  
pp. 745-749 ◽  
Author(s):  
RALF KEMMERLING ◽  
DENIS WEYLAND ◽  
TOBIAS KIESSLICH ◽  
ROMANA ILLIG ◽  
ECKHARD KLIESER ◽  
...  
Keyword(s):  
Linear Regression ◽  
Regression Model ◽  
Linear Regression Model ◽  
Gastrointestinal Stromal Tumors ◽  
Mitotic Rate ◽  
Ki 67 ◽  
Stromal Tumors ◽  
Robust Linear Regression

scholarly journals CLINICAL EXPERIENCE IN USING TARGETED THERAPY FOR DISSEMINATED GASTROINTESTINAL STROMAL TUMORS

2019 ◽  
Vol 18 (3) ◽  
pp. 109-113
Author(s):  
S. T. Adlejba ◽  
L. M. Kogonija ◽  
L. E. Gurevich ◽  
A. V. Sidorov
Keyword(s):  
Mass Spectrometry ◽  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Gastrointestinal Stromal Tumors ◽  
High Performance ◽  
Response To Therapy ◽  
Tandem Mass ◽  
Active Metabolites ◽  
Stromal Tumors

We report a case of disseminated gastrointestinal stromal tumor effectively treated with imatinib, a selective tyrosine kinase inhibitor.Background.Treatment of gastrointestinal stromal tumors (GIST ) still remains a clinical challenge. Since 2001 a breakthrough has occurred in the treatment of patients with GIST due to a successful use of imatinib, the targeted drug from the group of tyrosine kinase inhibitors, which is effective in the first line of inoperable and/or metastatic GIST , and is also used for neoadjuvant and adjuvant therapy for localized GIST . Genetic mutational analysis used for the correct prescription of targeted therapy suggests that it is inappropriate to administer imatinib in patients with a mutation in the succinate dehydrogenase gene and D842V mutation in the platelet-derived growth factor gene. However, in different regions of the Russian Federation, such diagnostic procedure may not always be available for a number of technical reasons. The lack of response to therapy and, consequently, the progression of the disease, may be associated with a decrease in the therapeutic concentration of imatinib in the blood plasma. Determination of the concentration of active metabolites of imatinib in the serum allows timely identification of potential causes of insufficient response to therapy and individual correction of the dose of the drug.Material and Methods.To assess a significance of the correlation between increasing/decreasing the dose of imatinib and achieving a therapeutic response, we used a laboratory high-performance liquid chromatography method to determine the concentration of imatinib in serum.Conclusion.Determination of a decreased concentration of active metabolites of imatinib in plasma by high-performance liquid chromatography with detection of tandem mass spectrometry method in a patient with disseminated GIST allowed us to correct the dose of the drug and achieve a positive effect with a duration of 51 months (since the dose was increased). The method of high-performance liquid chromatography with the detection of the method of tandem mass spectrometry is not an absolute alternative to gene mutation analysis, however, it can be effectively used for correction of the dose of imatinib in patients with GIST.

Usefulness of anti-phosphohistone H3 immunoreactivity to determine mitotic rate in gastrointestinal stromal tumors

2012 ◽  
Vol 5 (4) ◽  
pp. 91-97 ◽  
Author(s):  
Ahrong Kim ◽  
Dong Han Im ◽  
Kyungbin Kim ◽  
Jee Yeon Kim ◽  
Mee Young Sol ◽  
...  
Keyword(s):  
Gastrointestinal Stromal Tumors ◽  
Mitotic Rate ◽  
Stromal Tumors ◽  
Phosphohistone H3

The prognostic analysis of gastrointestinal stromal tumor

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 20534-20534 ◽  
Author(s):  
Y. Shi ◽  
C. Du ◽  
H. Fu ◽  
G. Zhao ◽  
y. Zhou
Keyword(s):  
Survival Rate ◽  
Gastrointestinal Stromal Tumor ◽  
Gastrointestinal Stromal Tumors ◽  
Cox Regression ◽  
Statistical Significance ◽  
Surgical Excision ◽  
Mitotic Rate ◽  
Stromal Tumor ◽  
Stromal Tumors ◽  
Prognostic Analysis

20534 Objective: To investigate the prognostic factor of gastrointestinal stromal tumor. Methods: The clinicopathological data of 103 patients with gastrointestinal stromal tumors were analyzed restrospectively. Life table, kaplan-meier survival rate and cox regression model were used to evaluate the prognostic factors. Results: The 1 year ,3 years and 5 years total survival rate of these 103 gastrointestinal stromal tumors was 86.3%, 51.7%, 42.8%. Tumor size, mitotic rate, primary organ of tumor and radical surgical excision or not were analyzed respectively, the difference is statistical significance (P<0.05). No significiant difference between the group of sex, age, immunohistochemistry expression and multi-organ resection or not. Conclusion: Flechers’ classification is rational, scientific, simple and feasible. Radical surgical excision is the best therapy to the primary gastrointestinal stomal tumor. No significant financial relationships to disclose.

scholarly journals Imatinib Regulates miR-483-3p and Mitochondrial Respiratory Complexes in Gastrointestinal Stromal Tumors

2021 ◽  
Vol 22 (19) ◽  
pp. 10600
Author(s):  
Wen-Kuan Huang ◽  
Hao Shi ◽  
Pinar Akçakaya ◽  
Katarina Zeljic ◽  
Anastasia Gangaev ◽  
...  
Keyword(s):  
Gastrointestinal Stromal Tumors ◽  
Underlying Mechanism ◽  
Therapeutic Strategies ◽  
Metabolic Adaptation ◽  
Imatinib Treatment ◽  
Loss Of Function ◽  
Stromal Tumors ◽  
Mitochondrial Respiratory Complex ◽  
Mitochondrial Respiratory

Metabolic adaptation to increased oxidative phosphorylation (OXPHOS) has been found in gastrointestinal stromal tumor (GIST) upon imatinib treatment. However, the underlying mechanism of imatinib-induced OXPHOS is unknown. Discovering molecules that mediate imatinib-induced OXPHOS may lead to the development of therapeutic strategies synergizing the efficacy of imatinib. In this study, we explored the role of microRNAs in regulating OXPHOS in GIST upon imatinib treatment. Using a microarray approach, we found that miR-483-3p was one of the most downregulated miRNAs in imatinib-treated tumors compared to untreated tumors. Using an extended series of GIST samples, we further validated the downregulation of miR-483-3p in imatinib-treated GIST samples by RT-qPCR. Using both gain- and loss-of-function experiments, we showed that miR-483-3p could regulate mitochondrial respiratory Complex II expression, suggesting its role in OXPHOS regulation. Functionally, miR-483-3p overexpression could rescue imatinib-induced cell death. These findings provide the molecular link for imatinib-induced OXPHOS expression and the biological role of miR-483-3p in regulating cell viability upon imatinib treatment.

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