Abstract
Long non-coding RNAs (lncRNAs) are a class of non-protein-coding RNAs essential to the occurrence and development of gastric cancer (GC). We aimed to identify critical lncRNA pairs to construct a prognostic model and assess its performances in prognosis and efficacy prediction in GC patients receiving immunotherapy and chemotherapy. We searched transcriptome and clinical data of GC patients from The Cancer Genome Atlas (TCGA) database. Autophagy-related lncRNAs were identified using co-expression network analysis, and lncRNA pairs with prognostic value were selected using pairwise transcriptome analysis. The gene pairs were subjected to LASSO algorithm for identification of optimal gene pairs for risk model construction. Patients were classified into the low-risk and high-risk groups with the RiskScore as a cutoff. Finally, 9 optimal gene pairs were identified in the LASSO algorithm model for construction of a lncRNA prognostic risk model. For predictive performances, it successfully predicted a shorter survival of high-risk patients than that obtained in low-risk individuals (P < 0.001). It showed moderate AUC (area under the curve) values for 1-, 2-, and 3-year overall survival prediction of 0.713 and could serve as an independent predictor for GC prognosis. Compared to the low-risk group, high-risk patients had higher expressions of marker genes for immune checkpoint inhibitors (ICIs) and showed higher sensitivity to the chemotherapy agents, rapamycin, bexarotene, and bicalutamide. Our findings demonstrate a robust prognostic model based on nine autophagy-related lncRNA pairs for GC. It acts as an independent predictor for survival and efficacy prediction of immunotherapy and chemotherapy in GC patients.
Highlights
gastric cancer (GC) is a common gastrointestinal malignancy originating from gastric mucosa epithelial cells, and it ranks fifth for cancer incidence and third for cancer deaths worldwide [1, 2]
Construction of a GC risk model based on autophagyrelated Long non-coding RNAs (lncRNAs) pairs We performed the pairwise transcriptome analysis of the 102 differential genes and found 2,895 autophagy-related lncRNA pairs showed significant differential expression in GC versus normal tissues
These genes were input to the LASSO algorithm, and nine optimal gene pairs associated with GC prognosis were confirmed using univariate Cox regression (Figure 2A, 2B) and visualized in forest plots of hazard ratios (Figure 2C, 2D)
Summary
GC is a common gastrointestinal malignancy originating from gastric mucosa epithelial cells, and it ranks fifth for cancer incidence and third for cancer deaths worldwide [1, 2]. The 2015 cancer statistics showed that GC has the third-highest cancer morbidity and the second-highest cancer mortality in China [3], ranking higher than most developed countries in Europe and North America [4]. In the Chinese population, patients with stage III GC make up 50%-60% of the total GC cases, a www.aging-us.com higher prevalence than that achieved in South Korea or Japan. The 5-year survival rate of Chinese patients is only 35.9%, significantly lower compared to 60%-70% in South Korea and Japan. Current management for advanced GC in China mainly incorporates palliative surgery, radiotherapy, chemotherapy, biological therapy (or immunotherapy), and traditional Chinese medicine. Immunotherapy has been proven to benefit advanced GC patients with no response to chemotherapy [5]. As growing clinical trials center on personalized treatment for GC patients, individualized prescription of chemotherapy or immunotherapy has been another challenge in China
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