Spatial downregulation of CD74 signatures may drive invasive component development in part-solid lung adenocarcinoma
Jia-Tao Zhang,
Juan Zhang,
Song-Rong Wang,
Li-Xu Yan,
Jing Qin,
Kai Yin,
Xiang-Peng Chu,
Meng-Min Wang,
Hui-Zhao Hong,
Zhi-Yi Lv,
Song Dong,
Ben-Yuan Jiang,
Xu-Chao Zhang,
Xiang Liu,
Qing Zhou,
Yi-Long Wu,
Wen-Zhao Zhong
Affiliations
Jia-Tao Zhang
Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China
Juan Zhang
Echo Biotech Co, Ltd, Beijing, China
Song-Rong Wang
Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China
Li-Xu Yan
Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China
Jing Qin
School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, Guangdong, China
Kai Yin
Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China
Xiang-Peng Chu
Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China
Meng-Min Wang
Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China
Hui-Zhao Hong
Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China
Zhi-Yi Lv
Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China
Song Dong
Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China
Ben-Yuan Jiang
Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China
Xu-Chao Zhang
Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China
Xiang Liu
Echo Biotech Co, Ltd, Beijing, China
Qing Zhou
Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China
Yi-Long Wu
Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China
Wen-Zhao Zhong
Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China; Corresponding author
Summary: Pulmonary nodules with part-solid imaging features manifest during the progression from preinvasive to invasive lung adenocarcinoma. To define the spatial composition and evolutionary trajectories of early-stage lung adenocarcinoma, we combined spatial transcriptomics (ST) and pathological annotations from 20 part-solid nodules (PSNs), four of which were matched with single-cell RNA sequencing. Two malignant cell populations (MC1 and MC2) were identified, and a linear evolutionary relationship was observed. Compared to MC2, the pre-existing malignant MC1 exhibited a lower metastatic signature, corresponding to the preinvasive component (lepidic) on pathology and the ground glass component on PSN imaging. Higher immune infiltration was observed among MC1 regions in ST profiles, and further analysis revealed that macrophages may be involved in this process through the CD74 axis. This work provides deeper insights into the evolutionary process and spatial immune cell composition behind PSNs and highlights the mechanisms of immune escape behind this adenocarcinoma trajectory.
