Comprehensive analysis to identify DNA damage response-related lncRNA pairs as a prognostic and therapeutic biomarker in gastric cancer

Yuan Yang; Lingshan Zhou; Xi Gou; Guozhi Wu; Ya Zheng; Min Liu; Zhaofeng Chen; Yuping Wang; Rui Ji; Qinghong Guo; Yongning Zhou; Yuan Yang; Lingshan Zhou; Xi Gou; Guozhi Wu; Ya Zheng; Min Liu; Zhaofeng Chen; Yuping Wang; Rui Ji; Qinghong Guo; Yongning Zhou

doi:10.3934/mbe.2022026

Mathematical Biosciences and Engineering

2022, Volume 19, Issue 1: 595-611. doi: 10.3934/mbe.2022026

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Research article

Comprehensive analysis to identify DNA damage response-related lncRNA pairs as a prognostic and therapeutic biomarker in gastric cancer

1.
The First Clinical Medical College, Lanzhou University, Lanzhou 730000, China
2.
Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou 730000, China
3.
Gansu Key Laboratory of Gastroenterology, Lanzhou University, Lanzhou 730000, China
4.
Department of Geriatrics Ward 2, The First Hospital of Lanzhou University, Lanzhou 730000, China

Academic Editor: Ulf Schmitz

Received: 18 September 2021 Accepted: 08 November 2021 Published: 18 November 2021

Objective
Gastric cancer (GC) is the fifth most common malignancy and the fourth leading cause of cancer-related mortality worldwide. The identification of valuable predictive signatures to improve the prognosis of patients with GC is becoming a realistic prospect. DNA damage response-related long noncoding ribonucleic acids (drlncRNAs) play an important role in the development of cancers. However, their prognostic and therapeutic values remain sparse in gastric cancer (GC).

Methods
We obtained the transcriptome data and clinical information from The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) cohort. Co-expression network analyses were performed to discover functional modules using the igaph package. Subsequently, lncRNA pairs were identified by bioinformation analysis, and prognostic pairs were determined by univariate analysis, respectively. In addition, we utilized least absolute shrinkage and selection operator (LASSO) cox regression analysis to construct the risk model based on lncRNA pairs. Then, we distinguished between the high- or low- risk groups from patients with GC based on the optimal model. Finally, we reevaluated the association between risk score and overall survival, tumor immune microenvironment, specific tumor-infiltrating immune cells related biomarkers, and the sensitivity of chemotherapeutic agents.

Results
32 drlncRNA pairs were obtained, and a 17-drlncRNA pairs signature was constructed to predict the overall survival of patients with GC. The ROC was 0.797, 0.812 and 0.821 at 1, 2, 3 years, respectively. After reclassifying these patients into different risk-groups, we could differentiate between them based on negative overall survival outcome, specialized tumor immune infiltration status, higher expressed immune cell related biomarkers, and a lower chemotherapeutics sensitivity. Compared with previous models, our model showed better performance with a higher ROC value.

Conclusion
The prognostic and therapeutic signature established by novel lncRNA pairs could provide promising prediction value, and guide individual treatment strategies in the future.
- DNA damage response,
- tumor immunity,
- lncRNA pairs,
- prognosis,
- therapy
Citation: Yuan Yang, Lingshan Zhou, Xi Gou, Guozhi Wu, Ya Zheng, Min Liu, Zhaofeng Chen, Yuping Wang, Rui Ji, Qinghong Guo, Yongning Zhou. Comprehensive analysis to identify DNA damage response-related lncRNA pairs as a prognostic and therapeutic biomarker in gastric cancer[J]. Mathematical Biosciences and Engineering, 2022, 19(1): 595-611. doi: 10.3934/mbe.2022026

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Abstract

Objective

Gastric cancer (GC) is the fifth most common malignancy and the fourth leading cause of cancer-related mortality worldwide. The identification of valuable predictive signatures to improve the prognosis of patients with GC is becoming a realistic prospect. DNA damage response-related long noncoding ribonucleic acids (drlncRNAs) play an important role in the development of cancers. However, their prognostic and therapeutic values remain sparse in gastric cancer (GC).

Methods

We obtained the transcriptome data and clinical information from The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) cohort. Co-expression network analyses were performed to discover functional modules using the igaph package. Subsequently, lncRNA pairs were identified by bioinformation analysis, and prognostic pairs were determined by univariate analysis, respectively. In addition, we utilized least absolute shrinkage and selection operator (LASSO) cox regression analysis to construct the risk model based on lncRNA pairs. Then, we distinguished between the high- or low- risk groups from patients with GC based on the optimal model. Finally, we reevaluated the association between risk score and overall survival, tumor immune microenvironment, specific tumor-infiltrating immune cells related biomarkers, and the sensitivity of chemotherapeutic agents.

Results

32 drlncRNA pairs were obtained, and a 17-drlncRNA pairs signature was constructed to predict the overall survival of patients with GC. The ROC was 0.797, 0.812 and 0.821 at 1, 2, 3 years, respectively. After reclassifying these patients into different risk-groups, we could differentiate between them based on negative overall survival outcome, specialized tumor immune infiltration status, higher expressed immune cell related biomarkers, and a lower chemotherapeutics sensitivity. Compared with previous models, our model showed better performance with a higher ROC value.

Conclusion

The prognostic and therapeutic signature established by novel lncRNA pairs could provide promising prediction value, and guide individual treatment strategies in the future.

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