GC is a multifactorial disease with heterogeneity, and can be classified clinically as early or advanced GC(Waldum and Fossmark, 2018). Several risk factors are involved in the occurrence and development of GC, such as environmental factors, ethnicity, dietary habits, and host genetic factors(Poorolajal et al., 2020; Rawla and Barsouk, 2019). Recently, a lot of studies have reported that lncRNAs play a vital role in the occurrence and development of GC due to the progression of bioinformatics analysis and third-generation sequencing technology(Jin, 2021; Wang et al., 2021; Yousefi et al., 2021). Moreover, increased studies have found that lncRNAs are also involved in the regulation of immune system in GC(Nie et al., 2020; Sun et al., 2021). However, the underlying mechanisms of immune related lncRNAs associated with the occurrence and development of GC remain undetermined. Therefore, a comprehensive function analysis of immune-related lncRNAs will help us better investigate their role, and develop prognostic signatures and immune therapeutic targets for GC patients.
In present study, 146 immune-related lncRNAs were obtained by Person correlation analysis between the differentially expressed lncRNAs and the immune genes from MSigDB in GC. Then, 5 immune-related lncRNAs (AP001528.2, LINC02542, LINC02526, PVT1 and LINC01094) were identified as prognosis-related lncRNAs by using univariate and multivariate Cox regression analysis. Subsequently, a risk score model was constructed based on these 5 immune-related lncRNAs, which was significantly associated with OS by survival analysis and had a satisfactory predictive value of 5-year survival for GC patients by ROC analysis. Moreover, the expression of AP001528.2, PVT1, LINC01094, and LINC02542 was significantly correlated with the depth of invasion and the distant metastasis in GC. In addition, the 5 immune-related lncRNAs risk score model can clearly distinguish the high- or low- risk group compared with the total gene expression or all immune-related lncRNAs through PCA analysis. Therefore, the present study proved that the 5 immune-related lncRNAs risk score model were novel biomarkers, and had a satisfactory predictive prognosis of GC patients. Furthermore, the 5 immune-related lncRNAs might be new immune therapeutic targets for GC patients in future.
Recently, several studies have discovered that immune-related lncRNAs are identified and have satisfactory capacity predict the prognosis of human malignancies. For instance, a seven immune-related lncRNAs prediction model was constructed in lung adenocarcinoma (LUAD), which had a satisfactorily predictive efficiency and guided the personalized treatment for LUAD patients(Li et al., 2020). Zhao K et al. have discovered that the signature of six immune-related lncRNAs are identified in bladder cancer, and closely associate with the prognosis for the patients with bladder cancer(Zhao et al., 2021). Therefore, these six immune-related lncRNAs might be immunotherapy targets for bladder cancer(Zhao et al., 2021). A nine immune-related lncRNAs prediction model was constructed in colon cancer, and closely related with overall survival for the patients with colon cancer, which could be defined as potential biomarkers affecting the prognosis of colon cancer(Lin et al., 2020). In present study, we firstly identified five immune-related lncRNAs (AP001528.2, LINC02542, LINC02526, PVT1 and LINC01094) in GC, and constructed a risk score model based on these immune-related lncRNAs. Furthermore, we found that GC patients with a higher risk score had a poorer overall survival than that with a lower risk score. Therefore, these five immune-related lncRNAs might be novel biomarkers to predict the prognosis, and immunotherapy targets for GC patients.
LncRNA PVT1 was found to be dysregulated in several human malignancies. For instance, PVT1 expression was significantly up-regulated in pancreatic ductal adenocarcinoma (PDAC) tissues compared with adjacent normal tissues. Meanwhile, patients with higher PVT1 expression level associated with shorter overall survival compared to those with lower PVT1 expression level(Huang et al., 2015). Similarly, the expression of PVT1 was higher in colon cancer tissues than that of adjacent tissues, and the higher PVT1 expression contributed to shorter disease-free survival and overall survival for the patients with colon cancer(Fan et al., 2018). In addition, PVT1 expression was dramatically increased in gastric cancer tissues compared with that in the normal control, and increased PVT1 expression resulted in poor overall survival and disease-free survival for the patients with gastric cancer(Yuan et al., 2016). However, we discovered that the overexpression of PVT1 was associated with a good prognosis for GC patients in present study. Therefore, it should be further verified potentially significant clinical implications of the PVT1 for GC patients in future.
Chen HY et al. have reported that the expression level of LINC01094 was prominently increased in ovarian cancer tissues compared with adjacent normal tissues, and LINC01094 overexpression promoted the viability, migration and invasion of ovarian cancer cells(Chen et al., 2021a). Consistently, LINC01094 was highly expressed in the clear cell renal cell carcinoma compared with adjacent normal tissues, and the LINC01094 overexpression was associated with a poor prognosis for the patients with clear cell renal cell carcinoma(Xu et al., 2020). In present study, we firstly found that the overexpression of LINC01094 was associated with a poor prognosis for GC patients.
Obviously, there were some shortcomings in present study. First, all the data were obtained based on online databases. Therefore, further studies should be performed to verify our findings. Second, we firstly discovered that the overexpression of AP001528.2, LINC02542 and LINC02526 was associated with a poor prognosis for GC patients. However, there was no report of these three immune-related lncRNAs involved in other human malignancies, nowadays. Therefore, the biological function and mechanisms of these immune-related lncRNA required further exploration in human malignancies. Third, it is important to explore the underlying mechanism of these five immune-related lncRNA involved in the occurrence and development of GC in vivo and in vitro in future.
In conclusion, we constructed a novel five immune-related lncRNAs risk score model which had a satisfactory predictive prognostic value for GC patients. Therefore, the five immune-related lncRNAs risk score model might be potential prognostic biomarkers and immunotherapy targets for GC patients in future.