Relevance and prognostic ability of Twist, Slug and tumor spread through air spaces in lung adenocarcinoma

Abstract

Background Tumor spread through air spaces (STAS) is a novel pathologic characteristic in lung adenocarcinomas that indicates invasive tumor behavior. We aimed to explore the relationship between Twist, Slug and STAS in lung adenocarcinoma and to investigate the potential relationship between epithelial‐mesenchymal transition (EMT) and STAS. Materials and methods Our study retrospectively analyzed 115 patients with resected lung adenocarcinomas to evaluate the relationship between Twist, Slug and STAS. STAS was diagnosed using hematoxylin‐eosin (H&E) staining. Immunohistochemistry was used to evaluate the expression levels of Slug and Twist. Results In this study, 56 (48.7%) patients had STAS, 40 (34.8%) patients had Slug overexpression, and 28 (24.3%) patients had Twist overexpression. Patients with either STAS or Slug and Twist overexpression experienced poor recurrence‐free survival (RFS) and overall survival (OS). There were significant associations between Twist overexpression, Slug overexpression and the presence of STAS. The logistic model further revealed that pathological stage, Twist overexpression and Slug overexpression were independent risk factors for STAS. A multivariate analysis that contained Twist, Slug, pathologic stage and STAS, showed that pathologic stage and STAS were independent prognostic factors for poor RFS and OS. Another multivariate model that contained Twist, Slug and pathologic stage, showed that pathologic stage, Twist overexpression and Slug overexpression were independent risk factors for poor RFS and OS. In the cohort with STAS, the multivariate analysis showed that pathologic stage and Twist overexpression were independent risk factors for poor survival. The subgroup analysis showed that patients with both Slug overexpression and Twist overexpression with STAS received a poor prognosis. Conclusions STAS, Slug and Twist were correlated with poor RFS and OS in resected lung adenocarcinomas. Additionally, STAS was correlated with the overexpression of Twist and Slug, which could potentially provide information on the mechanism of STAS.

Prognostic and Clinicopathological Value of Slug Expression in Breast Cancer: A Meta-analysis

“…Slug is associated with prognosis in a variety of cancer cells. Liu et al [30] and Song et al [31]found that slug is expressed more in lung cancer cells than in normal lung tissue, and high expression of slug in lung tumor cells is associated with poor survival and more aggressive clinicopathological parameters. Chang et al [32] and Gu et al [33] found that slug is highly correlated with the invasiveness and drug resistance of ovarian cancer cells.…”

Rosthorin A inhibits non-small cell lung cancer cell growth and metastasis through repressing epithelial-mesenchymal transition via downregulating Slug

“…Previous studies have shown that the overexpression of Twist reduces overall survival and recurrence-free survival in lung cancer patients [ 19 , 20 ]. Slug is a transcriptional factor of EMT with zinc finger structures, which plays a crucial role in the process of EMT, migration, invasion, metastasis, and sustain of stem cell-like characteristics of cancer cells, and it is related to the development of lung cancer [ 5 ]. As one of the key factors in the EMT process, Slug has been detected in many malignant tumors, and the high expression of Slug has been proved to be related to the clinical results of malignant tumors (such as lung cancer [ 21 ] and colorectal cancer [ 22 ]).…”

“…Therefore, many researchers turned to study lung cancer metastasis. Metastasis is thought to be associated with the expression of embryonic transcription factors Slug and Twist, which promote the invasion and metastasis of tumors-epithelial-mesenchymal transition (EMT) [ 5 ]. EMT is a process in which epithelial cells with polarity are transformed into stromal cells with migration ability, and the invasion and migration ability is acquired at the same time.…”

Comprehensive analysis for clarifying transcriptomics landscapes of spread through air spaces in lung adenocarcinoma

“…STAS is defined as tumor cells within air spaces in the lung parenchyma beyond the edge of the primary tumor (Eguchi et al, 2019;Qi et al, 2021). Notably, several studies have demonstrated that STAS is an independent factor indicating lung cancer recurrence and poor outcomes in patients (Yang et al, 2018;Liu et al, 2020;Onozato et al, 2021).…”

“…STAS is defined as tumor cells within air spaces in the lung parenchyma beyond the edge of the primary tumor ( Eguchi et al, 2019 ; Qi et al, 2021 ). Notably, several studies have demonstrated that STAS is an independent factor indicating lung cancer recurrence and poor outcomes in patients ( Yang et al, 2018 ; Liu et al, 2020 ; Onozato et al, 2021 ). Additionally, STAS is an insidious pattern of invasion that is invisible to pathologists on gross examination and surgeons on external analysis of tumor specimens at the time of surgery.…”