SMAD4 mutation correlates with poor prognosis in non-small cell lung cancer View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2020-12-10

AUTHORS

Yue Wang, Qianqian Xue, Qiang Zheng, Yan Jin, Xuxia Shen, Mu Yang, Xiaoyan Zhou, Yuan Li

ABSTRACT

SMAD4 is an intracellular signaling mediator of the TGF-β pathway. Its mutation was commonly observed in gastrointestinal cancers, such as pancreatic cancer. The loss of SMAD4 on immunohistochemical staining is often used to suggest a pancreaticobiliary differentiation in evaluating a metastatic adenocarcinoma with unknown origin. However, the function and molecular mechanism of SMAD4 in non-small cell lung cancer (NSCLC) development are largely unknown. Thus, we studied the correlation between SMAD4 mutations and clinico-molecular features in the patients with NSCLC. We reported the frequencies and prognostic values of SMAD4 mutations in a Chinese NSCLC cohort using next-generation sequencing. The NSCLC cases from several public databases, including The Cancer Genome Atlas and others, were also used in this study to elucidate SMAD4-related molecular partners and mechanisms. Integrated bioinformatics analyses were conducted, such as analysis of Gene Ontology enrichment analysis, gene set enrichment analysis (GSEA), and survival analysis. Immunohistochemistry showed that the tissues harboring SMAD4 mutations tended to show SMAD4 deficiency or loss, while SMAD4 expression was significantly reduced at all stages of NSCLC cases. We found that reduced SMAD4 expression was more frequent in the patients with poor disease-free survival and resistance to platinum-based chemotherapy. SMAD4 mutation was an independent risk factor for the survival of NSCLC patients. The expression of SMAD4 was associated with that of SMAD2. The GSEA showed that SMAD4 might promote NSCLC progression by regulating proliferation, adhesion, and immune response. In conclusion, these data suggest that SMAD4 mutation or loss as well as reduced expression can be used to identify the NSCLC patients with poor survival and resistance to platinum-based chemotherapy. SMAD4 may be a predictive marker or therapeutic target in NSCLC. The source code and user’s guide are freely available at Github: https://github.com/wangyue77-ab/smad4. More... »

PAGES

463-476

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41374-020-00517-x

DOI

http://dx.doi.org/10.1038/s41374-020-00517-x

DIMENSIONS

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PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/33303972


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102 origin
103 pancreatic cancer
104 partners
105 pathway
106 patients
107 platinum-based chemotherapy
108 poor disease-free survival
109 poor prognosis
110 poor survival
111 predictive marker
112 prognosis
113 prognostic value
114 progression
115 proliferation
116 public databases
117 resistance
118 response
119 risk factors
120 sequencing
121 source code
122 stage
123 staining
124 study
125 survival
126 survival analysis
127 target
128 therapeutic target
129 tissue
130 unknown origin
131 user guide
132 values
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