Identification and Application of a Novel Immune-Related lncRNA Signature on the Prognosis and Immunotherapy for Lung Adenocarcinoma

Abstract

Background: Long non-coding RNA (lncRNA) participates in the immune regulation of lung cancer. However, limited studies showed the potential roles of immune-related lncRNAs (IRLs) in predicting survival and immunotherapy response of lung adenocarcinoma (LUAD). Methods: Based on The Cancer Genome Atlas (TCGA) and ImmLnc databases, IRLs were identified through weighted gene coexpression network analysis (WGCNA), Cox regression, and Lasso regression analyses. The predictive ability was validated by Kaplan–Meier (KM) and receiver operating characteristic (ROC) curves in the internal dataset, external dataset, and clinical study. The immunophenoscore (IPS)-PD1/PD-L1 blocker and IPS-CTLA4 blocker data of LUAD were obtained in TCIA to predict the response to immune checkpoint inhibitors (ICIs). The expression levels of immune checkpoint molecules and markers for hyperprogressive disease were analyzed. Results: A six-IRL signature was identified, and patients were stratified into high- and low-risk groups. The low-risk had improved survival outcome (p = 0.006 in the training dataset, p = 0.010 in the testing dataset, p < 0.001 in the entire dataset), a stronger response to ICI (p < 0.001 in response to anti-PD-1/PD-L1, p < 0.001 in response to anti-CTLA4), and higher expression levels of immune checkpoint molecules (p < 0.001 in PD-1, p < 0.001 in PD-L1, p < 0.001 in CTLA4) but expressed more biomarkers of hyperprogression in immunotherapy (p = 0.002 in MDM2, p < 0.001 in MDM4). Conclusion: The six-IRL signature exhibits a promising prediction value of clinical prognosis and ICI efficacy in LUAD. Patients with low risk might gain benefits from ICI, although some have a risk of hyperprogressive disease.

New insights into immune cells in cancer immunotherapy: from epigenetic modification, metabolic modulation to cell communication

“… 270 Also, some pyroptosis‐related genes and immune‐related lncRNAs have been recognized as potential prognostic markers of cancer immunotherapy. 271 , 272 In addition, radiogenomic biomarkers to predict therapeutic response to PD1/PDL1 immunotherapy in NSCLC have also been discovered. 273 …”

“…270 Also, some pyroptosis-related genes and immune-related lncR-NAs have been recognized as potential prognostic markers of cancer immunotherapy. 271,272 In addition, radiogenomic biomarkers to predict therapeutic response to PD1/PDL1 immunotherapy in NSCLC have also been discovered. 273 In summary, cancer immunotherapy is a rapidly evolving field, and a growing number of potentially usable biomarkers for predicting and evaluating cancer immunotherapy have emerged.…”

“…In addition, the researchers also elucidated that tumor‐infiltrating B‐lymphocyte lncRNA signature can be used as an index of immune cell infiltration in TIME and lncRNA is expected to be used as a potential biomarker for the prediction of immunotherapy response in bladder cancer 270 . Also, some pyroptosis‐related genes and immune‐related lncRNAs have been recognized as potential prognostic markers of cancer immunotherapy 271,272 . In addition, radiogenomic biomarkers to predict therapeutic response to PD1/PDL1 immunotherapy in NSCLC have also been discovered 273 …”

Hyperprogressive disease in non-small cell lung cancer after PD-1/PD-L1 inhibitors immunotherapy: underlying killer

“…Furthermore, long non-coding RNA (lncRNA) plays a critical role in the immune regulation of LUAD and the immune-related lncRNAs (IRLs) manifest a promising prediction value of ICIs efficacy in LUAD. Patients with low risk might gain benefits from ICIs whereas some have a risk of HPD ( 45 ). Additionally, Liquid biopsy could be assisted to identify patients at high risk of HPD, and ctDNA may be a novel prognostic biomarker of PD-1 blockade ( 46 , 47 ).…”

A novel telomere-related gene prognostic signature for survival and drug treatment efficiency prediction in lung adenocarcinoma

“…In recent years, due to the progress of sequencing technology, some models based on genetic signatures have been explored to evaluate the prognosis of LUAD patients. These models have shown a promising predictive accuracy, and a few of them might also AGING indicate the potential carcinogenesis mechanism of LUAD [5][6][7].…”