Expression of DOG1 in peripheral blood cells of patients with gastrointestinal stromal tumor.

BACKGROUND AND STUDY AIMS: The diagnosis and surveillance of gastrointestinal stromal tumor (GIST) rely on pathology and immunochemistry (IHC), making it complicated and invasive. Noninvasive and convenient biomarkers of this disease need to be explored. The high specificity and sensitivity of IHC in detecting GIST 1 (DOG1) in biopsy indicate that it is also expressed in circulating tumor cells of the blood and may be an ideal biomarker for GIST. This aimed to detect the expression of DOG1 in peripheral blood cells (PBCs) and determine the relationship between DOG1 expression and clinical factors. PATIENTS AND METHODS: A total of 45 patients with GIST and 46 healthy controls (HCs) were recruited from the Second Affiliated Hospital of Nanchang University between December 2015 and June 2018. PBCs were isolated from peripheral venous blood by density gradient centrifugation. RNA was extracted from PBCs, and DOG1 mRNA was detected by quantitative reverse transcription polymerase chain reaction. DOG1 mRNA expression between GIST and HC was compared, and the relationship between clinical factors and DOG1 was also analyzed. RESULTS: DOG1 mRNA expression in PBCs was significantly higher in patients with GIST than that in HCs (3.326 [1.942-5.328] versus 0.744 [0.269-1.087], p < 0.01). The specificity and sensitivity were 88.9% and 89.1%, respectively (AUC = 0.912). Tumor diameter and risk of aggressive behavior were correlated with DOG1 expression, and other clinical factors (sex, age, location, number of phase-splitting cells, Ki-67 index, metastatic status) did not show any relationship with DOG1 expression. However, clinical factors, including tumor diameter and risk grade, were not independent factors in DOG1 expression when multivariate analysis was conducted. CONCLUSION: DOG1 expressions were significantly higher in patients with GIST than that in HCs. Tumor diameter and risk classification correlated with DOG1 expression but were not independent factors. DOG1 in PBCs is a promising noninvasive biomarker for GIST.

[Effect of Tiaoli Piwei needling technique on diabetic gastroparesis and transmembrane protein 16A].

OBJECTIVE: To observe the therapeutic effect of Tiaoli Piwei needling technique (acupuncture for regulating spleen and stomach) on diabetic gastroparesis (DGP), and to explore its possible mechanism. METHODS: A total of 128 patients with DGP were randomized into an observation group (64 cases, 4 cases dropped off) and a control group (64 cases, 4 cases dropped off). On the basis of intervention on controlling blood glucose by western medication, Tiaoli Piwei needling technique was adopted at Zhongwan (CV 12), Zusanli (ST 36), Yinlingquan (SP 9), Xuehai (SP 10), Sanyinjiao (SP 6), Diji (SP 8), etc. in the observation group, once a day. Mosapride citrate dispersible tablet 5 mg was given orally 3 times a day in the control group. The treatment was given 6 times a week in the both groups, and totally 4-week treatment was required. Before and after treatment, the DGP symptom score, serum content of transmembrane protein 16A (ANO1) were observed, and the clinical therapeutic effect and the safety were evaluated in the both groups. RESULTS: After treatment, the each subitem score (belching, abdominal distension, inappetence, nausea and vomiting, epigastric pain, abnormal defecation) and the total score of DGP symptom were decreased in both groups (P<0.05), the subitem scores of belching, abdominal distension, inappetence, nausea and vomiting and the total score in the observation group were lower than those in the control group (P<0.05). After treatment, the serum contents of transmembrane protein 16A were reduced in both groups (P<0.05), and that in the observation group was lower than the control group (P<0.05). The total effective rate was 86.7% (52/60) in the observation group, which was superior to 70.0% (42/60) in the control group (P<0.05). Subcutaneous hematoma occurred in 5 cases in the observation group, which was improved after cold compress without other particular intervention. CONCLUSION: The therapeutic effect of Tiaoli Piwei needling technique on improving symptoms in patients with diabetic gastroparesis is superior to mosapride citrate dispersible tablet, its mechanism may be related to alleviating the damage of interstitial cells of Cajal (ICC).

[Gastrointestinal stromal tumor and renal transplant]. / Tumor del estroma gastrointestinal y trasplante renal.

Gastrointestinal stromal tumor (GIST) accounts for nearly 1% of all gastrointestinal tumors. Its association with renal transplantation is not frequent. Approximately 95% of GIST show staining for CD177. DOG1 is a recently described monoclonal antibody that shows positivity even in the absence of CD177 staining. The diagnosis of GIST should be pursued because of the availability of very effective treatments with tyrosine-kinase inhibitors. Herein, we describe the case of a woman with renal transplant who presented a small bowel GIST and weak positivity for CD177, treated initially with surgery. Tumor recurrence was documented 3 years later and histopatology showed loss of CD177 staining and positivity for DOG1. She was treated with imatimib without further recurrence after five years of follow up.

Tumor del estroma gastrointestinal y trasplante renal / Gastrointestinal stromal tumor and renal transplant

El tumor estromal gastrointestinal (GIST) representa alrededor del 1% de todos los tumores digestivos y su aparición en pacientes trasplantados renales es infrecuente. Aproximadamente el 95% muestra tinción positiva para c-kit/CD117. DOG1 es un anticuerpo recientemente descrito que se sobre-expresa en los GIST, incluso en c-kit/ CD117 negativos. El diagnóstico preciso de GIST resulta imperativo, debido a la disponibilidad y la creciente eficacia de los inhibidores de la tirosina quinasa en estos tumores, incluso en el subgrupo c-kit/ CD117 negativo. Se presenta el caso de una mujer trasplantada renal inicialmente con GIST en intestino delgado y débil positividad para CD117 tratada con cirugía y recidiva tumoral a los tres años, pérdida de la expresión CD117 y tinción positiva para DOG1. Recibió tratamiento exitoso con imatimib sin presentar recaída tumoral durante un seguimiento de cinco años.

Gastrointestinal stromal tumor (GIST) accounts for nearly 1% of all gastrointestinal tumors. Its association with renal transplantation is not frequent. Approximately 95% of GIST show staining for CD177. DOG1 is a recently described monoclonal antibody that shows positivity even in the absence of CD177 staining. The diagnosis of GIST should be pursued because of the availability of very effective treatments with tyrosine-kinase inhibitors. Herein, we describe the case of a woman with renal transplant who presented a small bowel GIST and weak positivity for CD177, treated initially with surgery. Tumor recurrence was documented 3 years later and histopatology showed loss of CD177 staining and positivity for DOG1. She was treated with imatimib without further recurrence after five years of follow up.

Circulating tumor cells as a prognostic and predictive marker in gastrointestinal stromal tumors: a prospective study.

BACKGROUND: Circulating tumor cells (CTC) are prognostic and predictive for several cancer types. Only limited data exist regarding prognostic or predictive impact of CTC on gastrointestinal stromal tumor (GIST) patients. The aim of our study was to elucidate the role of CTC in GIST patients. RESULTS: A total of 121 GIST patients and 54 non-GIST samples were enrolled in the study. The cutoff value for ANO1 positive was 3*10-5 and 65 (54%) GIST patients were defined as ANO1 positive. ANO1s were more frequently detected in unresectable patients. Tumor size, mitotic count and risk level were associated with ANO1 detection in resectable GIST patients. The presence of ANO1 significantly correlated with poor disease-free survival (15.3 versus 19.6 months, p = 0.038). Most patients turned ANO1-negative after surgery and inversely, all 21 patients with recurrence turned ANO1-positive with high ANO1 expression levels. Moreover, in the neoadjuvant setting, decline of ANO1 expression level correlated with the response of imatinib. METHODS: Cells from peripheral blood mononuclear cells tested positive for anoctamin 1, calcium activated chloride channel, ANO1 (DOG1) were considered as tumor CTC of GISTs. The expression levels of ANO1 were determined using quantitative real-time polymerase chain reaction (qRT-PCR). The highest level of ANO1 expression in non-GIST samples was used as the "cutoff" value. CONCLUSION: ANO1 detection by qRT-PCR in peripheral blood is of clinical potential for monitoring recurrence and evaluating therapeutic efficacy of imatinib for GIST patients.