Exome Array Analysis Identifies Variants in SPOCD1 and BTN3A2 That Affect Risk for Gastric Cancer

Zhu, Meng; Yan, Caiwang; Ren, Chuanli; Huang, Xiao-Dan; Zhu, Xun; Gu, Heng; Wang, Meilin; Wang, Shouyu; Gao, Yong; Ji, Yong; Miao, Xiaoping; Yang, Ming; Chen, Jinfei; Du, Jiangbo; Huang, Tingpei; Jiang, Yue; Dai, Juncheng; Ma, Hongxia; Zhou, Jianwei; Wang, Zhaoming; Hu, Zhibin; Ji, Guozhong; Zhang, Zhengdong; Shen, Hongbing; Shi, Yongyong; Jin, Guangfu

doi:10.1053/j.gastro.2017.02.017

Cited by 58 publications

(56 citation statements)

References 48 publications

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“…BTN3A expression has rarely been investigated in the primary tumor context. 24,25,27,28,29,34 Based on the analysis of human primary tumor samples and novel patient-derived xenograft, we have now established that BTN3A overexpression and a dominant expression of the BTN3A2 isoform is strongly associated with a poor prognosis, in accordance with what was recently described in primary leukemic blasts 25 and in gastric cancer. 29 In this line, the overexpression of BTN3A2 gene was associated with an increased proliferation and invasion of gastric cancer cell lines.…”

Section: Discussionsupporting

confidence: 83%

“…26 While expressed by both immune cells and tumor cells, [24][25][26][27] BTN3A is more highly expressed in epithelial tumor tissues than in normal tissues, and is upregulated by tumor-associated soluble factors. 26,28,29 Our team has demonstrated that targeting BTN3A molecules with antagonist anti-BTN3A 103.2 or 108.5 monoclonal antibodies (mAb) can completely abrogate Vg9Vd2 T cell mediated lysis of tumors. 23,25 Conversely, the anti-BTN3A 20.1 mAb can strongly boost Vg9Vd2 T cells cytolytic function.…”

Section: Introductionmentioning

confidence: 99%

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BTN3A is a prognosis marker and a promising target for Vγ9Vδ2 T cells based-immunotherapy in pancreatic ductal adenocarcinoma (PDAC)

et al. 2017

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Vγ9Vδ2 T cells are anti-tumor immune effectors of growing interest in cancer including Pancreatic Ductal Adenocarcinoma (PDAC), an especially aggressive cancer characterized by a hypoxic and nutrient-starved immunosuppressive microenvironment. Since Butyrophilin 3 A (BTN3A) isoforms are critical activating molecules of Vγ9Vδ2 T cells, we set out to study BTN3A expression under both basal and stress conditions in PDAC primary tumors, and in novel patient-derived xenograft and PDAC-derived cell lines. BTN3A2 was shown to be the most abundant isoform in PDAC and was stress-regulated. Vγ9Vδ2 T cells cytolytic functions against PDAC required BTN3A and this activity was strongly enhanced by the agonist anti-BTN3A 20.1 mAb even under conditions of hypoxia. In PDAC primary tumors, we established that BTN3A expression and high plasma levels of soluble BTN3A were strongly associated with a decreased survival. These findings may have important implications in the design of new immunotherapeutic strategies that target BTN3A for treating PDAC.

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Section: Discussionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

BTN3A is a prognosis marker and a promising target for Vγ9Vδ2 T cells based-immunotherapy in pancreatic ductal adenocarcinoma (PDAC)

et al. 2017

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“…Recent study shows that SPOCD1 high expressed in bladder cancer and gastric cancer. 10,12 SPOCD1 promotes the proliferation and metastasis of glioma cells by PTX3. SPOCD1 promotes cell proliferation and inhibits cell apoptosis in osteosarcoma via VEGF-A.…”

Section: Discussionmentioning

confidence: 99%

“…10 SPOCD1 was overexpressed in gastric tumors and SPOCD1 knocking out reduced gastric cancer cell proliferation, invasion, and migration activities in vitro and in vivo. 11,12 Furthermore, SPOCD1 promoted cell proliferation and inhibited cell apoptosis through the regulation of vascular endothelial growth factor A (VEGF-A) in osteosarcoma. 13 The PI3K/Akt pathway is frequently changed in OC in an array comparative genomic hybridization studies.…”

Section: Introductionmentioning

confidence: 99%

<p>SPOCD1 accelerates ovarian cancer progression and inhibits cell apoptosis via the PI3K/AKT pathway</p>

Liu

Yang

Yan

et al. 2020

OTT

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Background: Ovarian cancer (OC) is the most common type of gynecological malignant tumors with poor prognosis. The spen paralogue and orthologue C-terminal domain containing 1 (SPOCD1) is a newly identified molecule that has been indicated to discriminate progressive in human solid tumors. However, the role of SPOCD1 in OC remains unknown. Methods: The expression of SPOCD1 in OC and non-cancerous tissue was detected by Realtime polymerase chain reaction and immunohistochemical staining. The expression of SPOCD1 in OC cells (SKOV3 and CAOV3) was also detected by immunohistochemical staining. The effect of SPOCD1 on cell proliferation was analyzed by Cell Counting Kit 8 and colony formation assay, and cell migration was analyzed by transwell assay. Apoptosis was analyzed by flow cytometry. The protein expression of SPOCD1, PTEN, PI3K, p-AKT, and mTOR in OC cells was measured by Western blot. Results: SPOCD1 expression was significantly upregulated in OC tissues compared with non-cancerous tissues (P<0.01), and was positively correlated to FIGO stage and tumor grade of OC. Also, SPOCD1 was significantly expressed in nucleus and cytoplasm of SKOV3 and CAOV3 cells. Kaplan-Meier analysis indicated that patients with high SPOCD1 expression had shorter overall survival (HR =1.512, 95%CI: 1.321-2.793, P=0.031) and progression-free survival (HR =1.875, 95%CI: 1.435-3.157, P=0.028). SPOCD1 was upregulated in OC SKOV3 and CAOV3 cells. Further investigation revealed that downregulation of SPOCD1 inhibited the SKOV3 and CAOV3 cells proliferation and migration. In addition, the deficit of SPOCD1 increased the apoptosis in SKOV3 and CAOV3 cells. PI3K/AKT pathway was inhibited by knockdown of SPOCD1 in SKOV3 and CAOV3 cells. Conclusions: Our data suggest that SPOCD1 may act as a carcinogenesis factor by activating the PI3K/AKT pathway to restrained cell apoptosis in OC.

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“…An illumine microarray study has shown that SPOCD1 independently discriminated progressive from non-progressive bladder cancer patients with a sensitivity of 79% and a specificity of 86% (AUC=0.83) (9). SPOCD1 was overexpressed in gastric tumors and knockout of SPOCD1 reduced gastric cancer cell proliferation, invasion and migration activities in vitro and in vivo (10). An exome array analysis has further identified that a low-frequency missense variant (rs1127549280) in the SPOCD1, at 1p35.2, was reproducibly associated with reduced risk of gastric cancer (odds ratio= 0.56; P=3.48x10 -8 ) (10).…”

Section: Introductionmentioning

confidence: 99%

SPOCD1 promotes cell proliferation and inhibits cell apoptosis in human osteosarcoma

Liang

Zhao

et al. 2017

Mol Med Report

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Osteosarcoma is the most common type of malignant bone tumors that typically affects adolescents and children. The spen paralogue and orthologue C‑terminal domain containing 1 (SPOCD1) is a newly identified molecule that has been indicated to discriminate progressive from non‑progressive bladder cancers. However, the role of SPOCD1 in human solid tumors remains largely unknown. In the present study, SPOCD1 was upregulated in clinical osteosarcoma tissues compared with adjacent non‑cancerous tissues. Furthermore, SPOCD1 was upregulated in osteosarcoma cell lines and expression was particularly increased in highly invasive cells MG63 and SAOS2. Further investigation revealed that downregulation of SPOCD1 inhibited the MG63 and SAOS2 osteosarcoma cell colony formation and proliferation capacity. In addition, cell apoptosis was promoted by knockdown of SPOCD1 in MG63 and SAOS2 cells. These effects were confirmed by measuring the Ki67 and PCNA expression. In addition, SPOCD1 positively regulated the expression of vascular endothelial growth factor A (VEGF‑A). Knockdown of VEGF‑A blunted SPOCD1 downregulation‑mediated inhibition of cell proliferation and induction of cell apoptosis. These results suggested that SPOCD1 may act as a pro‑oncogenic factor in osteosarcoma. Inhibition of VEGF may aid in treating osteosarcoma in clinic.

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Exome Array Analysis Identifies Variants in SPOCD1 and BTN3A2 That Affect Risk for Gastric Cancer

Abstract: We have associated variants at 1p35.2 and 6p22.1 with gastric cancer risk, indicating a role for SPOCD1 and BTN3A2 in gastric carcinogenesis.

Cited by 58 publications

References 48 publications

BTN3A is a prognosis marker and a promising target for Vγ9Vδ2 T cells based-immunotherapy in pancreatic ductal adenocarcinoma (PDAC)

BTN3A is a prognosis marker and a promising target for Vγ9Vδ2 T cells based-immunotherapy in pancreatic ductal adenocarcinoma (PDAC)

<p>SPOCD1 accelerates ovarian cancer progression and inhibits cell apoptosis via the PI3K/AKT pathway</p>

SPOCD1 promotes cell proliferation and inhibits cell apoptosis in human osteosarcoma

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