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

Abstract

BackgroundCirculating 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.ResultsA 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.MethodsCells 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.ConclusionANO1 detection by qRT-PCR in peripheral blood is of clinical potential for monitoring recurrence and evaluating therapeutic efficacy of imatinib for GIST patients.

Substituted 2-Acylaminocycloalkylthiophene-3-carboxylic Acid Arylamides as Inhibitors of the Calcium-Activated Chloride Channel Transmembrane Protein 16A (TMEM16A)

“…1–3 TMEM16A is overexpressed in some human cancers, 4, 5 and knockdown of TMEM16A inhibits cancer cell proliferation, cell cycle progression, and apoptosis. 6 TMEM16A was reported recently as a biomarker for gastrointestinal stromal and esophageal tumors, 7, 8 and TMEM16A expression is associated with good prognosis in PR-positive or HER2-negative breast cancer following tamoxifen treatment. 9 …”

Inhibition of Ca2+‐activated chloride channel ANO1 suppresses ovarian cancer through inactivating PI3K/Akt signaling

“…The ANO1 gene is localized on chromosome 11q13 locus that is frequently amplified in a number of human cancers, such as bladder cancer, breast cancer and head and neck squamous cell carcinoma (SCCHN) . ANO1 has been shown to be overexpressed in tumors including esophageal cancers, gastrointestinal stromal tumors, lung cancer, gastric cancer, breast cancer, prostate cancer, oral squamous cell carcinoma, pancreatic cancer, hepatocellular carcinoma and SCCHN cancer . ANO1 also contributes to breast cancer, HNSCC, ESCC and gastric cancer tumorigenesis by inducing MAPK and activating EGF receptor (EGFR) and calmodulin‐dependent protein kinase II (CAMKII) signaling, and TGF‐beta signaling .…”

“…The changes of gene expression profiles in PBMCs, in response to factors released by cancer cells, are reversible and specific to tissue types of cancers such as prostate cancer, breast cancer, lung cancer and colorectal cancer . A recent study has demonstrated that the gene expression level of the calcium‐activated chloride channel (CaCC) ANO1 in PBMCs is highly correlated with tumor size and differentiation of gastrointestinal stromal tumors (GIST), whereas most patients with GIST become ANO1‐negative after surgery or decline of ANO1 expression level in response to imatinib treatment . These observations suggest that detection of specific gene expressions in PBMCs can be of diagnostic and prognostic for cancers.…”

Biochemical Inhibition of DOG1/TMEM16A Achieves Antitumoral Effects in Human Gastrointestinal Stromal Tumor Cells In Vitro

“…activated through TNF-α was similar between the knockdown model and a biochemical inhibition (23). In GIST, high DOG1 expression is associated with poor prognosis and its high levels in circulating tumor cells can predict recurrence (26). The functional role of DOG1 is not fully understood, with only two studies having examined its role in GIST to date.…”