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

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PUBMED

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


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97 metastatic adenocarcinoma
98 molecular mechanisms
99 molecular partners
100 mutations
101 next-generation sequencing
102 non-small cell lung cancer
103 non-small cell lung cancer (NSCLC) development
104 ontology enrichment analysis
105 origin
106 pancreatic cancer
107 pancreaticobiliary differentiation
108 partners
109 pathway
110 patients
111 platinum-based chemotherapy
112 poor disease-free survival
113 poor prognosis
114 poor survival
115 predictive marker
116 prognosis
117 prognostic value
118 progression
119 proliferation
120 public databases
121 resistance
122 response
123 risk factors
124 sequencing
125 source code
126 stage
127 staining
128 study
129 survival
130 survival analysis
131 target
132 therapeutic target
133 tissue
134 unknown origin
135 user guide
136 values
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