Prognostic Role of High Stathmin 1 Expression in Patients with Solid Tumors: Evidence from a Meta-Analysis

Mao, Qingyan; Chen, Zhe; Wang, Kun; Xu, Rong; Liang, Hao; He, Xiaozhou

doi:10.1159/000493958

Cited by 17 publications

(22 citation statements)

References 21 publications

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“…Therefore, the physiological indicators related to the development and prognosis of esophageal cancer are required. In recent years, STMN1 has been reported to play a key role in the prognosis of esophageal cancer, suggesting that it is a cancer-associated gene [ 5,9,22,23]. In the present meta-analysis, six studies compared the OS of esophageal cancer patients with high vs. low expression of STMN1, and the results suggested that high STMN1 was associated with poor OS.…”

Section: Discussionmentioning

confidence: 62%

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Low STMN1 is associated with better prognosis in Asian patients with esophageal cancers: a meta-analysis

Cao

Zhang

Shen

et al. 2019

Preprint

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Background The role of STMN1 in the development and progression of esophageal carcinoma is not yet determined. The present study aimed to systematically evaluate the correlation between STMN1 and prognosis of patients with esophageal carcinoma. Methods Electronic databases including PubMed, Embase, the Cochrane library, and Chinese Biomedical Literature Database (CBM) were searched to identify studies evaluating the impact of STMN1 on the survival of esophageal cancer patients, without the language limitation. Two investigators screened the literature according to the inclusion and exclusion criteria and evaluated the quality of the included studies. The combined analysis was performed using RevMan5.3 software. Results A total of 8 studies, involving 1240 esophageal carcinoma patients, were included in this retrospective design. Meta-analysis showed that esophageal carcinoma patients with low STMN1 had a superior overall survival (OS) and disease-free survival (DFS) than those with high expression of STMN1. Compared to the high expression of STMN1, the 5-year survival rate was significantly higher in patients with low level of STMN1. Patients with high STMN1 expression had a higher risk of experiencing clinical grade III-IV disease, lymph node metastasis, and tumor invasion than those with low STMN1. Conclusion STMN1 is an indicator for the prognosis of esophageal carcinoma patients.

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Section: Discussionmentioning

confidence: 62%

“…Moreover, two meta-analyses [ 5,22] aimed to evaluate the role of STMN1 in various cancers. In 2016, the meta-analysis by Rong et al [ 5] disclosed the STMN1 expression patterns in several cancers and clari ed the connection between STMN1 and malignant diseases.…”

Section: Discussionmentioning

confidence: 99%

Low STMN1 is associated with better prognosis in Asian patients with esophageal cancers: a meta-analysis

Cao

Zhang

Shen

et al. 2019

Preprint

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“…In contrast, we found no significant association between high stathmin protein expression and reduced breast cancer specific survival in our in-house series (cohort 1), perhaps due to limited sample size. A recent meta-analysis addressed the prognostic role of stathmin in patients with solid cancers, including breast cancer 48 . In tumour-type subgroup analysis, stathmin was associated with worse disease-free survival in breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Stathmin expression associates with vascular and immune responses in aggressive breast cancer subgroups

Askeland

Wik

Finne

et al. 2020

Sci Rep

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Studies indicate that stathmin expression associates with PI3K activation in breast cancer, suggesting stathmin as a marker for targetable patient subgroups. Here we assessed stathmin in relation to tumour proliferation, vascular and immune responses, BRCA1 germline status, basal-like differentiation, clinico-pathologic features, and survival. Immunohistochemical staining was performed on breast cancers from two series (cohort 1, n = 187; cohort 2, n = 198), and mass spectrometry data from 24 cases and 12 breast cancer cell lines was examined for proteomic profiles. Open databases were also explored (TCGA, METABRIC, Oslo2 Landscape cohort, Cancer Cell Line Encyclopedia). High stathmin expression associated with tumour proliferation, p53 status, basal-like differentiation, BRCA1 genotype, and high-grade histology. These patterns were confirmed using mRNA data. Stathmin mRNA further associated with tumour angiogenesis, immune responses and reduced survival. By logistic regression, stathmin protein independently predicted a BRCA1 genotype (OR 10.0, p = 0.015) among ER negative tumours. Cell line analysis (Connectivity Map) implied PI3K inhibition in tumours with high stathmin. Altogether, our findings indicate that stathmin might be involved in the regulation of tumour angiogenesis and immune responses in breast cancer, in addition to tumour proliferation. Cell data point to potential effects of PI3K inhibition in tumours with high stathmin expression.Breast cancer is a heterogeneous disease with different molecular subtypes 1,2 . Among these, the basal-like category represents 10-15% of all cases. Most of the basal-like tumours are triple negative (ER−/PR−/HER2−), with high histological grade and usually a more aggressive clinical behaviour. Importantly, basal-like and triple negative breast cancers are also heterogeneous 3-5 , and current studies explore novel treatment targets and improved markers for these breast cancer subtypes. Notably, there is a strong association between cases arising in heterozygotes for pathogenic BRCA1 variants and a basal-like phenotype 6 . Henceforth, this genotype will be referred to as BRCA1 positive.Stathmin is a microtubule destabilizing protein important for the construction and function of the mitotic spindle 7,8 . Active, non-phosphorylated stathmin depolymerizes microtubules during interphase and late mitosis 8,9 . Tight regulation of stathmin function through phosphorylation, and de-phosphorylation is necessary for optimal function of the mitotic spindle and orderly progression through the cell cycle 9-11 . In addition to its role in mitosis, stathmin is involved in the regulation of other cellular processes such as epithelial polarity, apoptosis, and cell motility 12-14 . Further, Segatto and colleagues recently demonstrated that stathmin is required for ∆16HER2-driven early breast cancer development in mice 14 .In breast cancer, high stathmin levels are associated with aggressive features 15-17 and reduced survival 17-20 , and overexpression is reported in a variety of other...

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“…has been suggested to be a marker of tumor resistance to taxanes (13)(14)(15)(16). LK-2 and RERF-LC-AI cells were treated with or without TXT and Ramucirumab in single and combination treatment settings, and then subjected to RNA-seq analysis.…”

Section: Stxbp4 As a Novel Therapeutic Targetmentioning

confidence: 99%

“…Needless to say, the TP53 gene is a key factor in tumorigenesis and tumor resistance to therapy in lung cancer (5)(6)(7)(8)(9), and ΔNp63 is a putative diagnostic marker for LSCC (12). STMN1 (oncoprotein 18 and LAP18) has been suggested to be a potent predictive marker for a variety of cancers including LSCC (13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

Syntaxin binding protein 4 as a novel therapeutic target and an effective biomarker for better treatment selection in lung squamous cell carcinoma: A theranostic study

Erkhem-Ochir

Kaira²,

Kawabata‐Iwakawa

et al. 2020

Preprint

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Abstract Background Lung squamous cell carcinoma (LSCC) remains a challenging disease to treat, and further improvements in prognosis are dependent upon the identification of LSCC-specific therapeutic biomarkers and/or targets. We previously found that Syntaxin Binding Protein 4 (STXBP4) plays a crucial role in lesion growth and, therefore, clinical outcomes in LSCC patients through regulation of tumor protein p63 (TP63) ubiquitination. Methods To clarify the potential of STXBP4 as a novel therapeutic target and/or a predictive biomarker of therapeutic response, we assessed its prognostic impact of the protein in 144 LSCC patients and examined whether its action pathway is distinct from those of currently used drugs in in vitro experiments including RNA-seq analysis through comparison with the other putative exploratory targets and/or markers. Results Kaplan–Meier analysis revealed that, along with ΔNp63 (an isoform of TP63) and vascular endothelial growth factor receptor 2 (VEGFR2), STXBP4 expression signified a worse prognosis in LSCC patients, both in terms of overall survival (OS, P = 0.002) and disease-free survival (DFS, P = 0.041). Multivariate analysis demonstrated STXBP4 to be an independent prognostic factor for poor DFS, while VEGFR2 (P < 0.001) and TP63 (ΔNp63, P < 0.05) were independent prognostic factors for poor OS. The action pathway of STXBP4 on suppression of TP63 (ΔNp63), which results in the and inhibits tumor growth, was unique: Ingenuity pathway analysis using the knowledge database and our RNA-seq analysis in human LSCC cell lines indicated that 35 pathways were activated or inactivated in association with STXBP4, but the action pathway of STXBP4 was distinct from those of other current drug targets: STXBP4, TP63 and KDR (VEGFR2 gene) formed a cluster independent from other target genes of tumor protein p53 (TP53), tubulin beta 3 (TUBB3), stathmin 1 (STMN1) and cluster of differentiation 274 (CD274: programmed cell death 1 ligand 1, PD-L1). STXBP4 itself appeared not to be a potent predictive marker of individual drug response, but we found that TP63, main action target of STXBP4, might be involved in drug resistance mechanisms of LSCC. Conclusion STXBP4 could afford a unique therapeutic target and a key to the development of precision medicine for LSCC patients.

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Prognostic Role of High Stathmin 1 Expression in Patients with Solid Tumors: Evidence from a Meta-Analysis

Cited by 17 publications

References 21 publications

Low STMN1 is associated with better prognosis in Asian patients with esophageal cancers: a meta-analysis

Low STMN1 is associated with better prognosis in Asian patients with esophageal cancers: a meta-analysis

Stathmin expression associates with vascular and immune responses in aggressive breast cancer subgroups

Syntaxin binding protein 4 as a novel therapeutic target and an effective biomarker for better treatment selection in lung squamous cell carcinoma: A theranostic study

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