Constructing a new prognostic signature of gastric cancer based on multiple data sets

ABSTRACT

In order to explore new prediction methods and key genes for gastric cancer. Firstly, we downloaded the 6 original sequencing data of gastric cancer on the Illumina HumanHT-12 platform from Array Expression and Gene Expression Omnibus, and used bioinformatics methods to identify 109 up-regulated genes and 271 down-regulated genes. Further, we performed univariate Cox regression analysis of prognostic-related genes, then used Lasso regression to remove collinearity, and finally used multivariate Cox regression to analyze independent prognostic genes (MT1M, AKR1C2, HEYL, KLK11, EEF1A2, MMP7, THBS1, KRT17, RPESP, CMTM4, UGT2B17, CGNL1, TNFRSF17, REG1A). Based on these, we constructed a prognostic risk proportion signature, and found that patients with high-risk gastric cancer have a high degree of malignancy. Subsequently, we used the GSE15459 data set to verify the signature. By calculating the area under the recipient operator characteristic curve of 5-year survival rate, the test set and verification set are 0.739 and 0.681, respectively, suggesting that the prognostic signature has a moderate prognostic ability. The nomogram is used to visualize the prognostic sig-nature, and the calibration curve verification showed that the prediction accuracy is higher. Finally, we verified the expression and prognosis of the hub gene, and suggested that HEYL, MMP7, THBS1, and KRT17 may be potential prognostic biomarkers.

KEYWORDS:

• Gastric cancer
• prognostic signature
• bioinformatics
• nomogram

Highlights

• 380 differential genes were screened from 118 normal and 827 gastric cancer samples.

• Fourteen independent prognostic genes in gastric cancer were identified, and a prognostic signature was constructed with good predictive performance.

• Constructed a nomogram for forecasting 1-5 years, and verified its accuracy in predicting survival.

• HEYL, MMP7, THBS1, KRT17 may be potential biomarkers of gastric cancer.

Disclosure of potential conflicts of interest

The authors declare that they have no competing interests.

Authors’ contributions

Liqiang Zhou and Fei Zeng conceived, designed, analyzed the data, and Hao Lu write the manuscript. Qi Zhou, Shihao Li helped to search for some relevant papers for this research. You Wu and Yiwu Yuan generated the figures and tables. Lin Xin guided the research process and review the manuscript. All authors read and approved the final manuscript.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

National Natural Science Foundation of China, [Grant/Award Numbers: 81872480, 81760549, 81560492]; Key R&D Projects in Jiangxi Province, [Grant/Award Numbers: 20203BBG73056]; Science and Technology Research Project of Education Department of Jiangxi Province, [Grant/Award Number: GJJ180024].

Notes on contributors

Liqiang Zhou

Liqiang ZhouM.D., Ph.D., Department of General Surgery, The Second Affiliated Hospital of Nanchang University, the research direction is targeted therapy of gastrointestinal tumors.

Hao Lu

Hao LuM.D., Ph.D., Department of General Surgery, The Second Affiliated Hospital of Nanchang University, the research direction is the clinical treatment of gastrointestinal tumors.

Fei Zeng

Fei ZengM.D., Department of General Surgery, The Second Affiliated Hospital of Nanchang University, the research direction is the clinical treatment of gastrointestinal tumors.

Qi Zhou

Qi Zhou M.D., Department of General Surgery, The Second Affiliated Hospital of Nanchang University, the research direction is the clinical treatment of gastrointestinal tumors.

Shihao Li

Shihao LiM.D., Department of General Surgery, The Second Affiliated Hospital of Nanchang University, the research direction is the clinical treatment of gastrointestinal tumors.

You Wu

You Wu M.D., Department of General Surgery, The Second Affiliated Hospital of Nanchang University, the research direction is the clinical treatment of gastrointestinal tumors.

Yiwu Yuan

Yiwu Yuan M.D., Ph.D., Department of General Surgery, The Second Affiliated Hospital of Nanchang University, the research direction is the clinical treatment of gastrointestinal tumors.

Lin Xin

Lin Xin M.D., Ph.D., Department of General Surgery, The Second Affiliated Hospital of Nanchang University, the research direction is gastrointestinal tumor metabolism and targeted therapy.