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MTA2 is one of 14 Transcription factors predicting recurrence free survival in gastric cancer and promotes cancer progression by targeting MCM5.

ABSTRACT: Gastric cancer (GC) is a leading cause of cancer-related death worldwide. Transcription factors (TFs) are essential gene expression regulators, and play critical roles in cancer development. However, the biological actions and prognostic value of TFs in GC remain unclear. In this study, we identified a risk model based on a 14-TF signature to predict recurrence-free survival in patients with GC. We further analyzed the ability of 14-TF to predict recurrence-free survival time in GC and found that a higher expression level of metastasis-associated protein 2 (MTA2) was associated with shorter overall survival and disease-free survival time in GC. Through in vitro and in vivo experiments, we demonstrated that MTA2 significantly promotes GC growth and metastasis. Furthermore, we identified MTA2 binding to the promoter of minichromosome maintenance deficient 5 (MCM5), thereby promoting GC progression. Overall, these findings strongly support the prognostic potential of the 14-TFs signature and suggest that targeting MTA2 may be a promising strategy to treat GC.

SUBMITTER: Li A

PROVIDER: S-EPMC9891871 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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MTA2 is one of 14 Transcription factors predicting recurrence free survival in gastric cancer and promotes cancer progression by targeting MCM5.

Li Anshu A Guo Yan Y Yin Zhijie Z Liu Xinghua X Xie Gengchen G

Journal of Cancer 20230101 2

Gastric cancer (GC) is a leading cause of cancer-related death worldwide. Transcription factors (TFs) are essential gene expression regulators, and play critical roles in cancer development. However, the biological actions and prognostic value of TFs in GC remain unclear. In this study, we identified a risk model based on a 14-TF signature to predict recurrence-free survival in patients with GC. We further analyzed the ability of 14-TF to predict recurrence-free survival time in GC and found tha ...[more]

PMID: 36741260

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Project description:BackgroundWe have preliminarily reported MTA2 expression in gastric cancer and its biological functions by using knockdown cell models, while the molecular mechanisms of MTA2 in regulating malignant behaviors are still unclear.MethodsMTA2 overexpression models were established by transfection assay in gastric cancer cells BGC-823 and MKN28. Cell proliferation assay, colony formation in soft agar, wound-healing assay and transwell migration assay were performed with MTA2 overexpression and negative control (NC) cells. Subcutaneous xenografts and pulmonary metastasis models by BGC-823/MTA2 and BGC-823/NC cells were used to observe the capacity of growth and metastasis in vivo. Differential gene expression in MTA2 knockdown and overexpression cells was analyzed by microarrays. IL-11, which demonstrated as differential expression in microarray, was detected by real-time PCR, western blot, ELISA and immunohistochemistry staining. Recombinant human IL-11 (rhIL-11) was administrated in cell proliferation and colony formation as rescue assay.ResultsThe numbers of colonies in soft agar were significantly more in BGC-823/MTA2 and MKN28/MTA2 cells, comparing with those in their NC cells. Capabilities of cell proliferation, wound-healing and cell migration were not significantly changed in MTA2 overexpression cells. The sizes of subcutaneous xenografts and pulmonary metastases of BGC-832/MTA2 cells were significantly larger than those in BGC-823/NC group. Differential expression of IL-11 was identified by genome expression microarray both in MTA2 knockdown and overexpression cells. IL-11 expression was elevated in BGC-823/MTA2 cells, whereas reduced in SGC-7901/shMTA2 cells. Administration of rhIL-11 recovered colony formation capacity of SGC-7901/shMTA2 cells.ConclusionsMTA2 overexpression enhances colony formation and tumor growth of gastric cancer cells, but not plays important role in cancer cell migration and metastasis. IL-11 is one of the downstream effectors of MTA2 in regulating gastric cancer cells growth.

Project description:BackgroundVenous invasion (VI) in pathological examination of surgically resected gastric cancer (GC) may predict postoperative recurrence, but there are no objective criteria for VI grading.Methods157 GC patients (pathological stages I 82, II 34, and III 41) who underwent surgery with curative intent were analyzed. VI was graded in pathological examination by elastica van Gieson staining based on the number of VIs per glass slide as follows: v0, 0; v1, 1-3; v2, 4-6; and v3, ≥ 7. Filling-type invasion in veins with a minor axis of ≥ 1 mm increased the grade by 1. The association of VI grade with prognosis was statistically analyzed.ResultsRecurrence increased with VI grade (v0 1.5%, v1 29.6%, v2 41.7%, v3 78.6%). VI grade as well as pathological (p) tumor, node, metastasis (TNM) stage was a significant recurrence predictor by the multivariate Cox analysis. VI grade was implicated in hematogenous and peritoneal recurrences independent of pTNM stage but not in nodal recurrence. GC was then divided into two tiers, without indication of adjuvant chemotherapy (AC) (pStage I, pT1 and pT3N0) and with AC indication (pStages remaining II/III), based on the ACTS-GC trial, which is common in Japan and East Asia. VI grade was a significant recurrence predictor in both tiers. v2/v3 revealed a significantly worse recurrence-free survival (RFS) than v0/v1 in GC without AC indication. v0/v1 exhibited RFS rate exceeding 95% even after 5 years but that of v2/v3 fell around 70% within one year postoperatively, suggesting that AC may be considered for this tier with v2/v3. GC with AC indication exhibited dismal RFS according to the VI grade. RFS rate fell below 80% within one year postoperatively when VI was positive, while recurrence was not observed in v0, which was, however, rare in this tier (10.9%). Differentiation grade did not significantly affect postoperative prognosis in both tiers.ConclusionsVI grade was a significant predictor of postoperative GC recurrence irrespective of the AC indication based on the ACTS-GC study and this VI grading system could be applied in future studies of adjuvant therapy in GC presently deemed without AC indication in Japan.

Project description:BackgroundAfter radical surgery, early detection of recurrence and metastasis is a crucial factor in enhancing the prognosis and survival of patients with gastric cancer (GC). Therefore, assessing the risk of recurrence in gastric cancer patients and determining the timing for postoperative recurrence is crucial.MethodsThe clinicopathological data of 521 patients with recurrent gastric cancer, who underwent radical gastrectomy at Zhejiang Cancer Hospital between January 2010 and January 2017, were retrospectively analyzed. These patients were randomly divided into two groups: a training group (n = 365) and a validation group (n = 156). In the training set, patients were further categorized into early recurrence (n = 263) and late recurrence (n = 102) groups based on a 2-year boundary. Comparative analyses of clinicopathological features and prognoses were conducted between these two groups. Subsequently, a nomogram for predicting early recurrence was developed and validated.ResultsIn this study, the developed nomogram incorporated age, serous infiltration, lymph node metastasis, recurrence mode, and the tumour marker CA19-9. In the training cohort, the area under the curve (AUC value) was 0.739 (95% CI, 0.682-0.798), with a corresponding C-index of 0.739. This nomogram was subsequently validated in an independent validation cohort, yielding an AUC of 0.743 (95% CI, 0.652-0.833) and a C-index of 0.743. Furthermore, independent risk factors for prognosis were identified, including age, absence of postoperative chemotherapy, early recurrence, lymph node metastasis, abdominal metastasis, and vascular cancer embolus.ConclusionIndependent risk factors for gastric cancer recurrence following radical surgery were utilized to construct a nomogram for predicting early relapse. This nomogram effectively assesses the risk of recurrence, aids in treatment decision-making and follow-up planning in clinical settings, and demonstrated strong performance in the validation cohort.

Dataset Information

MTA2 is one of 14 Transcription factors predicting recurrence free survival in gastric cancer and promotes cancer progression by targeting MCM5.

Publications

MTA2 is one of 14 Transcription factors predicting recurrence free survival in gastric cancer and promotes cancer progression by targeting MCM5.

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