Biopic Tang's team and collaborators found that mixed-lineage tumor cells are widespread in patients with non-small cell lung cancer and revealed their biological characteristics

Lung cancer is one of the most morbid and mortal malignancies in the world, with about 1.

On August 13, 2022, professor Tang Fuhui's team from the Biomedical Frontier Innovation Center (BIOPIC) of Peking University and the team of Professor Wang Jie of the Cancer Hospital of the Chinese Academy of Medical Sciences and the team of academician Hejie published a research paper entitled "Molecular profiling of human non-small cell lung cancer by single-cell RNA-seq" at Genome Medicine

The study had 4 main findings:

1.

The researchers used high-precision single-cell transcriptome sequencing technology to analyze

Figure 1.

Previous single-cell transcriptome sequencing data based on the 10x Genomics platform have often been difficult to identify mixed-lineage tumor cells

Figure 2.

2.

The production of mixed-lineage tumor cells may be related to the abnormal differentiation of tumor cells, revealing the origin relationship between mixed-lineage tumor cells and single-lineage tumor cells in the same patient, which is the basis for

Figure 3.

Due to the limited number of sequenced cells and detected mitochondrial mutation sites in the study, it is not yet possible to determine the specific direction of progress of mixed-lineage tumor cells and single-lineage tumor cells, but the researchers speculate that in a non-small cell lung cancer patient, the most likely thing is that the normal epithelial cells of a specific lineage first transform into single-lineage tumor cells during early cancer, and then some of the tumor cells are further transformed into mixed-lineage tumor cells, obtaining stronger cell plasticity

3.

Mixed-lineage tumor cells have both molecular signatures of two or even three different lung cancer tumor subtypes, suggesting that they have strong cell plasticity and higher gene expression program disorders, which is likely to be one of the reasons for the failure of clinical treatment and tumor recurrence of non-small cell lung cancer

Figure 4.

4.

The study identified 73 marker genes with high specific expression in mixed-lineage tumor cells relative to single-lineage tumor cells, including cell mesenchymal-related genes FN1, TGFBI, COL1A1, and AKR1B1, SPRR1B, and keratin genes KRT6A, KRT19, KRT17, etc

Figure 5.
Functional study of the mixed-lineage tumor cell marker gene AKR1B1

In summary, the study used high-precision single-cell transcriptome sequencing technology to deeply analyze the molecular characteristics of tumor cells in 16 human primary non-small cell lung cancer patients, and found a new class of mixed-lineage tumor cells, which are widely present
in non-small cell lung cancer patients.
It was further confirmed that in the same non-small cell lung cancer patient, mixed lineage tumor cells and single-lineage tumor cells came from common tumor precursor cells
.
This suggests that mixed-lineage tumor cells are very malleable and may be easy to switch phenotypes between single-lineage and mixed-lineage states, which provides a possible explanation
for the easy recurrence and easy drug resistance of non-small cell lung cancer.
This study provides new clues for the more accurate classification of tumor subtypes of non-small cell lung cancer, and has important guiding significance for the diagnosis and treatment of patients with non-small cell lung cancer with high mixed lineage characteristics in the
future.

Qingqing Li, Dr.
Rui Wang, postdoctoral fellows at the School of Life Sciences of Peking University, and Dr.
Zhenlin Yang of cancer hospital of Chinese Academy of Medical Sciences are the tie-in first authors
of the paper.
Professor Tang Fuhui, Professor Wang Jie and Academician He Jie are the co-corresponding authors of the paper, and this research is supported
by the Beijing High-tech Innovation Center, the National Natural Science Foundation of China, the Beijing Natural Science Foundation of China, and the Innovation Team Development Program of the Ministry of Education.

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