Premium
Dramatically changed immune‐related molecules as early diagnostic biomarkers of non‐small cell lung cancer
Author(s) -
Ye Xiangdong,
Zhang Ni,
Jin Yanxia,
Xu Bo,
Guo Chanyuan,
Wang Xueqing,
Su Yanting,
Yang Qing,
Song Jiaqi,
Yu Wenhui,
Cheng Pengfei,
Cheng Liming,
Gong Yongsheng,
Fu Xiangning,
Sun Hui
Publication year - 2020
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.15051
Subject(s) - immune system , lung cancer , medicine , cancer , immunology , oncology
Non‐small cell lung cancer ( NSCLC ) is the main type of lung cancer, with a low 5‐year survival rate because of the absence of effective clinical biomarkers for early diagnosis. Based on the immunosurveillance theory, we proposed that changes in the immune system are more pronounced than tumour‐associated antigens during the early stage of cancer. Therefore, a new strategy was designed to screen early diagnostic biomarkers from peripheral leukocytes in early‐stage NSCLC s with transcriptome sequencing. A total of 358 immune‐related differentially expressed genes were identified between early‐ NSCLC patients and healthy individuals. Orosomucoid‐1 ( ORM 1, a acute phase protein), the total ORM and chitotriosidase‐1 (involved in degradation of chitobiose) were selected for further verification in 210 serum samples by western blotting, ELISA and nephelometry immunoassay (based on immuno‐scatter turbidmetry). Receiver operating characteristic curve analysis show that ORM 1 and total ORM have excellent diagnostic efficacies, with area under the curve of 0.862 and 0.920, respectively, which significantly distinguished very early‐ NSCLC ( IA ) from healthy samples. Flow cytometry results showed that CD 15 + neutrophils made up 73% of ORM 1 + peripheral leukocytes. In mouse lung cancer model, serum ORM 1, but not liver ORM 1, changed significantly in the early stage of NSCLC . ORM 1 expression in peripheral leukocytes was regulated by TGF ‐β and mediated by the TGF ‐β/Smad signalling pathway. Our results indicated that combined ORM and TGF ‐β could be a promising clinical biomarker in the diagnosis of early NSCLC .