Profiles of immune infiltration in lung adenocarcinoma and their clinical significant: A gene‐expression–based retrospective study

Abstract

Lung cancer is one of the fatal tumors. The tumor microenvironment plays a key role in regulating tumor progression. To figure out the role of tumor microenvironment in lung adenocarcinoma (LUAD), ESTIMATE algorithm was used to evaluate the immune scores in LUAD. Patients with low immune scores had a worse overall survival (OS) compared with high immune scores. Using RNA‐Seq data of 489 patients in The Cancer Genome Atlas (TCGA), differentially expressed genes (DEGs) were identified between high‐ and low‐immune score groups. Based on the DEGs, nine‐gene signature was constructed by the least absolute shrinkage and selection operator Cox regression model in TCGA set. The signature demonstrated significant prognostic value in both TCGA and Gene Expression Omnibus database. Multivariate Cox regression analyses indicated that nine‐genes signature was an independent prognostic factor. Subgroup analysis also revealed a robust prognostic ability of nine‐gene signature. A nomogram with a C‐index of 0.722 had a favorable power for predicting 3‐, 5‐, and 10‐year survival for clinical use by integrating nine‐gene signature and other clinical features. Co‐expression and functional enrichment analysis showed that nine‐gene signature was significantly associated with immune response and provided potential profound molecules for revealing the mechanism of tumor initiation and progression. In conclusion, we revealed the significance of immune infiltration and built a novel nine‐gene signature as a reliable prognostic factor for patients with LUAD.

Peer Review #1 of "Tumor microenvironment related novel signature predict lung adenocarcinoma survival (v0.1)"

“…And LUAD, as the most common type of lung cancer, is able to account for more than half of the morbidity and mortality of the lung cancer patient. 28,29 Currently, growing evidence has suggested that TME plays a pivotal role in tumor initiation and progression, 27,30 especially the recent immunocheckpoint inhibitors have noticeable effects on lung adenocarcinoma. However, patient prognosis and disease progression involved with TME related genes in LUAD have not been elucidated clearly.…”

“…Meanwhile, to explore the significance of these genes simultaneous changes for LUAD, we constructed and validated a risk assessment model that predicted survival of LUAD based on 106 genes.The prognostic model achieved robust predictive ability by combing with the clinical parameter we filtrated by multivariate Cox regression analysis.Recently, we notice that there are other prognostic model build by immune gene in LUAD 27 , however, compared with their prognostic model, the prognostic model we build have some advantages. First of all, we constructed the model by factor analysis.…”

Integrative modeling of multi-omics data for predicting tumor mutation burden in lung cancer patients

“…High TMB indicates the presence of more neoantigens in the tumor microenvironment, which promote the in ammatory response and result in the alteration of transcriptomic and epigenetic signature [47]. It has been proved that gene expression signatures in the tumor microenvironment were associated with the prognosis in NSCLC [48][49][50][51]. In agreement with previous studies, the differentially expressed genes between TMB-H and TMB-L patients identi ed in this study were found to enrich in the immune-related damaged DNA binding, nuclear division, nuclear chromosome segregation, organelle ssion, single-stranded DNA binding, ribonucleoprotein complex binding and pyrimidine metabolism (Additional le 2: Figure S2) [52][53][54][55][56].…”

New Insights on Old Biomarkers Involved in Tumor Microenvironment Changes and Their Diagnostic Relevance in Non-Small Cell Lung Carcinoma

“…Changes in the TME, remodeling of the extracellular matrix (ECM), pro-and anti-inflammatory processes, and cell metabolism are affected by neoplastic progression, but they also affect further progression and metastasis of the tumor. These changes can be examined by evaluating particular inflammatory and metabolic markers, which, in turn, may be considered diagnostic biomarkers [13][14][15][16][17][18].…”

“…Created with BioRender.com and Affinity Designer. TME is a complex mixture of tumor cells, extracellular matrix, and an inflammatory microenvironment including immune cells and cytokines that plays an essential part in tumorigenesis and progression [14,17,27]. The unrestricted proliferation of cancer cells influences TME, manifesting itself, among other things, in increased glucose uptake.…”