Construction and testing of a risk prediction classifier for cardia carcinoma

Author:

Liu Zhiqiang12345,Xia Ganshu4,Liang Xiaolong4,Li Shoumiao4,Gong Yanxin4,Li Baozhong4ORCID,Deng Jingyu123

Affiliation:

1. Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer , Tianjin 300060 , P.R. China

2. Key Laboratory of Cancer Prevention and Therapy , Tianjin 300060 , P.R. China

3. Tianjin’s Clinical Research Center for Cancer , Tianjin 300060 , P.R. China

4. Department of Gastric Surgery, Anyang Tumor Hospital , Anyang City 455000 , P.R. China

5. Tianjin Medical University , Tianjin 300070 , P.R. China

Abstract

Abstract Objectives This research aimed to construct a prediction model for stages II and III cardia carcinoma (CC), and provide an effective preoperative evaluation tool for clinicians. Methods CC mRNA expression matrix was obtained from Gene Expression Omnibus and The Cancer Genome Atlas databases. Non-negative matrix factorization was used to cluster data to obtain subgroup information, and weighted gene co-expression network analysis was used to uncover key modules linked to different subgroups. Gene-set enrichment analysis analyzed biological pathways of different subgroups. The related pathways of multiple modules were scrutinized with Kyoto Encyclopedia of Genes and Genomes. Key modules were manually annotated to screen CC-related genes. Subsequently, quantitative real-time polymerase chain reaction assessed CC-related gene expression in fresh tissues and paraffin samples, and Pearson correlation analysis was performed. A classification model was constructed and the predictive ability was evaluated by the receiver operating characteristic curve. Results CC patients had four subgroups that were associated with brown, turquoise, red, and black modules, respectively. The CC-related modules were mainly associated with abnormal cell metabolism and inflammatory immune pathways. Then, 76 CC-elated genes were identified. Pearson correlation analysis presented that THBS4, COL14A1, DPYSL3, FGF7, and SVIL levels were relatively stable in fresh and paraffin tissues. The area under the curve of 5-gene combined prediction for staging was 0.8571, indicating good prediction ability. Conclusions The staging classifier for CC based on THBS4, COL14A1, DPYSL3, FGF7, and SVIL has a good predictive effect, which may provide effective guidance for whether CC patients need emergency surgery.

Funder

Tianjin Key Medical Discipline (Specialty) Construction Project

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,General Medicine

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