Significantly different immunological score in lung adenocarcinoma and squamous cell carcinoma and a proposal for a new immune staging system

Abstract

TNM stage is not enough to accurately predict the prognosis of patients with non-small cell lung cancer (NSCLC). This study aimed to establish the Immunoscore (IS) in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), separately, and propose a new staging system in NSCLC. We used the multiplex fluorescent immunohistochemistry (mIHC) technology to detect 17 immune biomarkers of 304 patients with NSCLC. The LASSO-COX regression model was used to establish the IS NSCLC in the training cohorts. The IS NSCLC was then validated in the validation cohort. The constructed IS LUAD contained three immune features: CD4 + CD73 + core of tumor (CT) , PD-L1 + CT , and IDO + invasive margin (IM). IS LUSC also contained two immune features: CD8 + CD39 − CD73 − CT , CD8 + Tim-3 + IM. In the training cohort, significant prognostic differences were found upon comparing low-IS NSCLC patients with high-IS NSCLC patients. For LUAD, the 5-y disease-free survival (DFS) rates were 54.7% vs. 8.1% and the 5-y overall survival (OS) rates were 82.4% vs. 36% (all P< .0001). For LUSC, the 5-y DFS rates were 74.0% vs. 14.7% and the 5-y OS rates were 78.2% vs. 17.6% (all P< .0001). Multivariate analyses indicated that IS NSCLC was an independent indicator for prognosis. Finally, we combined IS NSCLC with clinicopathological factors to establish a TN-I staging system and two nomogram models for clinical use. The TN-I stage had better prediction accuracy than TNM stage. The newly established IS LUAD and IS LUSC were completely different, and both were excellent indicators for the prognostic prediction. The TN-I stage could effectively improve prognostic accuracy and facilitate clinical application.

Integrative Multi-Omics Analysis of Identified NUF2 as a Candidate Oncogene Correlates With Poor Prognosis and Immune Infiltration in Non-Small Cell Lung Cancer

“…Previous studies have found that the immunoscores of lung squamous cell carcinoma and lung adenocarcinoma are significantly different, and the different tumor-infiltrating immune cell indicate different prognosis in LUSC and LUAD ( 20 , 21 ). So we analyze immune correlation of NUF2 in LUSC and LUAD respectively.…”

Hepcidin Upregulation in Lung Cancer: A Potential Therapeutic Target Associated With Immune Infiltration

“…Three distinct subtypes of LUAD were introduced in 2014, including proximal inflammatory (PI), proximal proliferative (PP), and terminal respiratory unit (TRU) ( 43 ). LUAD usually arises from the distal airway, while LUSC is associated with more proximal airways ( 44 ). LUSC is generally more strongly associated with smoking and inflammatory diseases than LUAD ( 44 ).…”

“…LUAD usually arises from the distal airway, while LUSC is associated with more proximal airways ( 44 ). LUSC is generally more strongly associated with smoking and inflammatory diseases than LUAD ( 44 ). In general, LUAD grows more slowly and has smaller lumps than its contemporaneous counterpart LUSC but tends to metastasize at an early stage ( 45 ).…”

CD73 Severed as a Potential Prognostic Marker and Promote Lung Cancer Cells Migration via Enhancing EMT Progression

“…Notably, Inoue, Y et al’s study reported that high CD73 expression was an independent unfavorable prognostic marker in LUAD ( Inoue et al, 2017 ). However, Zeng, Z et al’s study reported that CD73 were associated with favorable prognosis in LUAD ( Zeng et al, 2020 ). Thus, the prognostic value of CD73 in LUAD still needed further studies.…”