Association between tissue origin classification and the clinical features and molecular phenotypes of nonsmall cell...

Lung cancer is the most common malignancy in humans and the leading cause of cancer-related deaths worldwide. Nonsmall cell lung cancer (NSCLC), the primary histologic type, is categorized into lung adenocarcinoma (LUAD) and lung squamous cell carcinoma based on immunohistochemical thyroid transcription factor-1 and P40 status. LUAD is morphologically classified into five histological subtypes, based on physician experience, which can lead to confusion among pathologists and clinicians. Histological subtypes serve as crucial markers for lung cancer development and hold significant clinical value for cancer diagnosis, prognosis, and treatment response prediction.

Identifying the various subtypes of NSCLC has become pivotal for enhancing diagnostic standards and patient prognosis.

In this study, we proposed a novel classification of NSCLC tissues into five subtypes (bronchial epithelial carcinoma, bronchiolar alveolar carcinoma, alveolar cell carcinoma, secretory adenocarcinoma, and mucinous adenocarcinoma) based on tissue origin. Furthermore, mRNA chip screening and next-generation sequencing revealed that these five subtypes exhibit distinct gene expression patterns and mutation signatures.

This study proposes a novel NSCLC classification model designed to incorporate gene signatures into tissue origin-based histopathological subtypes, complementing the World Health Organization classification, and enhancing both diagnostic accuracy and clinical practicability.