Lung cancer (LC) represents a frequently occurring cancer globally . Targeted drugs have achieved significant efficacy in treating "oncogenic driver mutations" with in-depth research on tumor pathogenesis and therapeutic strategies in lung cancer. These drugs mainly improve the survival rate of lung cancer patients by targeting the EGFR-TKI mutation. Gefitinib and Erlotinib are the first clinically approved agents to treat LC, which achieve favorable outcomes in PFS relative to chemotherapy[18, 19].
Additionally, applying PD-1/PD-L1 inhibitors ushers in the novel path to treat cancer cases. Such ICIs display persistent clinical activity among advanced cancer cases, and their emergence greatly improves cancer patient prognosis. Therefore, they are introduced in treating some solid tumors, like hepatocellular carcinoma (HCC), triple-negative breast cancer (TNBC), non-small-cell lung cancer (NSCLC), colorectal carcinoma (CRC), and melanoma [20, 21]. Compared with chemotherapy, pembrolizumab (the PD-1 antibody) and atezolizumab (the PD-L1 antibody) are found previously to enhance patient survival . This new therapeutic approach raises the question of identifying treatment-responsive cases. Immunohistochemistry (IHC) has been previously suggested as the predicting factor for treatment responses in patients through the detection of PD-L1 level on cancer cell surface [23, 24]. Unfortunately, since the response rate to therapy is around 20%, not all the patients with abnormal PD-1 and PD-L1 expression respond to treatment and depict improved tumor prognosis. Although most patients with an initial response subsequently progress [25, 26], little is known about PD-1’s resistance mechanism within LC. More and more studies have been conducted to analyze genomics with regard to PD-1 response, like elevated tumor mutational burden (TMB), changes in DNA damage response and repair (DDR) genes , and the aberrant expression of long non-coding RNAs. Moreover, LIMIT, a previously unknown cancer immunogenic lncRNA, could rescue MHC-I expression through the LIMIT-GBP-HSF1 signaling axis and suggest a promising immunotherapy approach against cancer . Another study identified lncRNA AC007255.1 to be the prognostic IRlncRNA in esophageal cancer (EC).
However, the relationship between immune-related lncRNAs and lung cancer remains unclear. Clinicians and researchers have attempted to explore markers that could identify patients benefiting from immunotherapy. In addition, no creditable biomarkers have been developed clinically. Consequently, this work first analyzed IRGs within LC based on the TCGA-GDC database, retrieved 17 IRlncRNAs, and later established 6 IRlncRNAs expression levels. Subsequently, this work found that 6 IRlncRNAs interacted with other factors as possible independent prognostic factors determined using univariate as well as multivariate regression. Moreover, they were also positively related to tumor clinicopathological features, like age, TNM and sex. The outcomes suggested that these six immune-related lncRNAs could become novel markers of lung cancer prognosis, provide new ideas, and open new research directions for developing therapeutic strategies for tumor patients. According to functional analysis, risk score was associated with DNA repair and cell cycle.
Our study had certain limitations: (1) The TCGA dataset was randomly and equally divided as training and validation sets, and this might lead to possible study bias. (2) There were significant differences in LC, healthy and paraneoplastic samples collected in TCGA database, making it impossible to differentially analyze 6 IRlncRNAs in LC compared with healthy tissues. (3) This work did not validate functional roles of those 6 IRlncRNAs, therefore, more studies should be conducted for further validation. Therefore, the biological functions of these six lncRNAs in lung cancer and their possible molecular mechanisms leading to tumor progression will be investigated through subsequent research.