The prognostic role of MAC30 in advanced gastric cancer patients receiving platinum-based chemotherapy

Wu, Xiaohong; Zhou, Feiqing; Ji, XiuHai; Ye, Shan; Mao, Xuhua; Fu, Yan; Chen, Ruhua; Ding, Hui; Fu, Xingli

doi:10.2217/fon-2017-0426

Cited by 6 publications

(4 citation statements)

References 17 publications

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“…Numerous studies demonstrated that TMEM97 was ubiquitously expressed in a wide variety of normal human tissues and cancer. TMEM97 mRNA and/or proteins was significantly increased in breast, colon, gastric, esophageal, lung, ovarian cancer and prostate cancer [ 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ], but decreased in meningiomas, pancreatic and renal cancer [ 27 , 37 ]. TMEM97 upregulation in certain tumors and downregulation in others suggests that this protein plays a distinct role in human malignancies.…”

Section: Biological Characteristics and Functions Of σ 2mentioning

confidence: 99%

The Biological Function of Sigma-2 Receptor/TMEM97 and Its Utility in PET Imaging Studies in Cancer

Zeng

Riad

Mach

2020

Cancers

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The sigma-2 receptor was originally defined pharmacologically and recently identified as TMEM97. TMEM97 has been validated as a biomarker of proliferative status and the radioligand of TMEM97, [18F]ISO-1, has been developed and validated as a PET imaging biomarker of proliferative status of tumors and as a predictor of the cancer therapy response. [18F]ISO-1 PET imaging should be useful to guide treatment for cancer patients. TMEM97 is a membrane-bound protein and localizes in multiple subcellular organelles including endoplasmic reticulum and lysosomes. TMEM97 plays distinct roles in cancer. It is reported that TMEM97 is upregulated in some tumors but downregulated in other tumors and it is required for cell proliferation in certain tumor cells. TMEM97 plays important roles in cholesterol homeostasis. TMEM97 expression is regulated by cholesterol-regulating signals such as sterol depletion and SREBP expression levels. TMEM97 regulates cholesterol trafficking processes such as low density lipoprotein (LDL) uptake by forming complexes with PGRMC1 and low density lipoprotein receptor (LDLR), as well as cholesterol transport out of lysosome by interacting with and regulating NPC1 protein. Understanding molecular functions of TMEM97 in proliferation and cholesterol metabolism will be important to develop strategies to diagnose and treat cancer and cholesterol disorders using a rich collection of TMEM97 radiotracers and ligands.

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Section: Biological Characteristics and Functions Of σ 2mentioning

confidence: 99%

The Biological Function of Sigma-2 Receptor/TMEM97 and Its Utility in PET Imaging Studies in Cancer

Zeng

Riad

Mach

2020

Cancers

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“…Although immunotherapy is in full swing now, chemotherapy is still the cornerstone in the first-line therapy of advanced gastric carcinoma. Except for several single proteins ( 31 , 32 ), there has been no assessable clinical biomarker with prognostic value on chemotherapy in advanced gastric carcinoma. In our study, using TMB as a novel biomarker we divided patients into two groups and presented different clinical outcomes when treated with first-line chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of tumor mutation burden in patients with advanced gastric cancer receiving first-line chemotherapy

et al. 2023

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BackgroundTumor mutation burden (TMB) is a promising biomarker positively associated with the benefit of immunotherapy and that might predict the outcome of chemotherapy. We described the prognostic value of TMB in advanced gastric cancer and explored the underlying mechanism.MethodsWe enrolled 155 TMB-evaluated advanced gastric cancer patients and analyzed the relationship between clinicopathological characteristics and both overall survival (OS) and progression-free survival (PFS) among 40 patients treated with first-line chemotherapy. We further verified the distribution of TMB and analyzed the potential mechanism underlying the prognosis based on The Cancer Genome Atlas (TCGA) database.ResultsAmong the 155 patients, 29 (18.7%) were TMB-high (TMB ≥ 10), roughly the same as the proportion in the TCGA data. Of the 40 patients receiving first-line chemotherapy, the median OS (7.9 vs. 12.1 months; HR 3.18; p = 0.0056) and PFS (4.4 vs. 6.2 months; HR 2.94; p = 0.0099) of the tissue-tested TMB (tTMB)-high patients were inferior to those of the tTMB-low patients. Similarly, unfavorable median OS (9.9 vs. 12.1 months; HR 2.11; p = 0.028) and PFS (5.3 vs. 6.5 months; HR 2.49; p = 0.0054) were shown in the blood-tested TMB (bTMB)-high than in the bTMB-low patients. The Cox analysis demonstrated that both tTMB-high and bTMB-high were significant independent predictors of dreadful OS and PFS. The differentially expressed genes (DEGs) according to TMB status were most significantly enriched in the downregulated metabolic pathway among the TMB-high patients.ConclusionsTMB-high advanced gastric cancer patients accounted for around one-sixth and had a poorer prognosis than TMB-low patients when treated with first-line chemotherapy. The potential mechanism might be the downregulated metabolic activity in TMB-high patients.

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“…[ 11,12 ] MAC30 has been shown to be dysregulated in multiple cancers and is related to cancer progression, metastasis, treatment tolerance, and prognosis. [ 13–19 ] The downregulation of MAC30 effectively represses proliferation and invasion in cancer cells by affecting multiple signaling pathways. [ 20–22 ] This suggests that MAC30 is a potential and attractive anticancer target, which may be used for the development of tumor therapies.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of MAC30 exerts antitumor effects in nasopharyngeal carcinoma via affecting the Akt/GSK‐3β/β‐catenin pathway

Zhang

Tian

Gao

et al. 2022

J Biochem & Molecular Tox

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Meningioma‐associated protein 30 (MAC30) is a vital modulator of malignant transformation in numerous cancers. Yet, the involvement of MAC30 in nasopharyngeal carcinoma (NPC) is undetermined. This study was devoted to the study of the function of MAC30 in NPC, along with the molecular mechanism of its involvement in disease progression. This study showed an elevated level of MAC30 in NPC tissues and cell lines. MAC30 silencing impeded the proliferation, colony formation, and invasion of NPC cells, while MAC30 upregulation had the opposite effects. MAC30 regulated the Wnt/β‐catenin pathway via affecting the protein kinase B (Akt)/glycogen synthase kinase‐3β axis. Akt inhibition markedly abrogated the MAC30‐mediated activation of the Wnt/β‐catenin pathway. Restoration of β‐catenin reversed MAC30 silencing‐induced tumor‐inhibiting effects. Knockdown of MAC30 weakened the tumorigenic potential of NPC cells in vivo. This study elucidates the fact that inhibition of MAC30 produces antitumor effects in NPC via affecting the Akt/Wnt/β‐catenin pathway.

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The prognostic role of MAC30 in advanced gastric cancer patients receiving platinum-based chemotherapy

Abstract: MAC30 could play as a potential biomarker for prognosis of GC with platinum-based chemotherapy.

Cited by 6 publications

References 17 publications

The Biological Function of Sigma-2 Receptor/TMEM97 and Its Utility in PET Imaging Studies in Cancer

The Biological Function of Sigma-2 Receptor/TMEM97 and Its Utility in PET Imaging Studies in Cancer

Prognostic value of tumor mutation burden in patients with advanced gastric cancer receiving first-line chemotherapy

Inhibition of MAC30 exerts antitumor effects in nasopharyngeal carcinoma via affecting the Akt/GSK‐3β/β‐catenin pathway

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