PMID- 34976204
OWN - NLM
STAT- MEDLINE
DCOM- 20220310
LR  - 20220310
IS  - 1838-7640 (Electronic)
IS  - 1838-7640 (Linking)
VI  - 12
IP  - 2
DP  - 2022
TI  - Single-cell RNA sequencing reveals a pro-invasive cancer-associated fibroblast 
      subgroup associated with poor clinical outcomes in patients with gastric cancer.
PG  - 620-638
LID - 10.7150/thno.60540 [doi]
AB  - Background: The protumor activities of cancer-associated fibroblasts (CAFs) 
      suggest that they are potential therapeutic targets for the treatment of cancer. 
      The mechanism of CAF heterogeneity in gastric cancer (GC) remains unclear and has 
      slowed translational advances in targeting CAFs. Therefore, a comprehensive 
      understanding of the classification, function, activation stage, and spatial 
      distribution of the CAF subsets in GC is urgently needed. Methods: In this study, 
      the characteristics of the CAF subsets and the dynamic communication among the 
      tumor microenvironment (TME) components regulated by the CAF subsets were 
      analyzed by performing single-cell RNA sequencing of eight pairs of GC and 
      adjacent mucosal (AM) samples. The spatial distribution of the CAF subsets in 
      different Lauren subtypes of GC, as well as the neighborhood relations between 
      these CAF subsets and the protumor immune cell subsets were evaluated by 
      performing multistaining registration. Results: Tumor epithelial cells exhibited 
      significant intratumor and intertumor variabilities, while CAFs mainly exhibited 
      intratumor variability. Moreover, we identified four CAF subsets with different 
      properties in GC. These four CAF subsets shared similar properties with their 
      resident fibroblast counterparts in the adjacent mucosa but also exhibited 
      enhanced protumor activities. Additionally, two CAF subsets, inflammatory CAFs 
      (iCAFs) and extracellular matrix CAFs (eCAFs), communicated with adjacent immune 
      cell subsets in the GC TME. iCAFs interacted with T cells by secreting 
      interleukin (IL)-6 and C-X-C motif chemokine ligand 12 (CXCL12), while eCAFs 
      correlated with M2 macrophages via the expression of periostin (POSTN). eCAFs, 
      which function as a pro-invasive CAF subset, decreased the overall survival time 
      of patients with GC. Conclusions: iCAFs and eCAFs not only exhibited enhanced 
      pro-invasive activities but also mobilized the surrounding immune cells to 
      construct a tumor-favorable microenvironment. Therefore, inhibiting their 
      activation restrains the GC 'seed' and simultaneously improves the 'GC' soil, 
      suggesting that it represents a promising therapeutic strategy for the treatment 
      of GC.
CI  - (c) The author(s).
FAU - Li, Xuechun
AU  - Li X
AD  - Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School 
      of Basic Medicine Peking Union Medical College, Peking Union Medical College 
      Hospital, Center of Excellence in Tissue Engineering Chinese Academy of Medical 
      Sciences, Beijing Key Laboratory (No. BZO381), Beijing, People's Republic of 
      China.
FAU - Sun, Zhao
AU  - Sun Z
AD  - Department of Medical Oncology, Peking Union Medical College Hospital, Chinese 
      Academy of Medical Sciences, Beijing, China.
FAU - Peng, Gongxin
AU  - Peng G
AD  - Center for Bioinformatics, Institute of Basic Medical Sciences, Chinese Academy 
      of Medical Sciences, School of Basic Medicine, Peking Union Medical College, 
      Beijing, 100005, China.
FAU - Xiao, Yi
AU  - Xiao Y
AD  - Department of General Surgery, Peking Union Medical College Hospital, Chinese 
      Academy of Medical Sciences, Beijing, China.
FAU - Guo, Junchao
AU  - Guo J
AD  - Department of General Surgery, Peking Union Medical College Hospital, Chinese 
      Academy of Medical Sciences, Beijing, China.
FAU - Wu, Bin
AU  - Wu B
AD  - Department of General Surgery, Peking Union Medical College Hospital, Chinese 
      Academy of Medical Sciences, Beijing, China.
FAU - Li, Xiaoyi
AU  - Li X
AD  - Department of General Surgery, Peking Union Medical College Hospital, Chinese 
      Academy of Medical Sciences, Beijing, China.
FAU - Zhou, Weixun
AU  - Zhou W
AD  - Department of Pathology, Peking Union Medical College Hospital, Chinese Academy 
      of Medical Sciences, Beijing, China.
FAU - Li, Jiarui
AU  - Li J
AD  - Department of Medical Oncology, Peking Union Medical College Hospital, Chinese 
      Academy of Medical Sciences, Beijing, China.
FAU - Li, Zhe
AU  - Li Z
AD  - Department of Gynecologic Oncology, National Cancer Center/ National Clinical 
      Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences 
      and Peking Union Medical College, Beijing, China.
FAU - Bai, Chunmei
AU  - Bai C
AD  - Department of Medical Oncology, Peking Union Medical College Hospital, Chinese 
      Academy of Medical Sciences, Beijing, China.
FAU - Zhao, Lin
AU  - Zhao L
AD  - Department of Medical Oncology, Peking Union Medical College Hospital, Chinese 
      Academy of Medical Sciences, Beijing, China.
FAU - Han, Qin
AU  - Han Q
AD  - Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School 
      of Basic Medicine Peking Union Medical College, Peking Union Medical College 
      Hospital, Center of Excellence in Tissue Engineering Chinese Academy of Medical 
      Sciences, Beijing Key Laboratory (No. BZO381), Beijing, People's Republic of 
      China.
FAU - Zhao, Robert Chunhua
AU  - Zhao RC
AD  - Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School 
      of Basic Medicine Peking Union Medical College, Peking Union Medical College 
      Hospital, Center of Excellence in Tissue Engineering Chinese Academy of Medical 
      Sciences, Beijing Key Laboratory (No. BZO381), Beijing, People's Republic of 
      China.
AD  - School of Life Sciences, Shanghai University, 99 Shangda Road, Shanghai 200444, 
      China.
FAU - Wang, Xiaoyue
AU  - Wang X
AD  - Center for Bioinformatics, Institute of Basic Medical Sciences, Chinese Academy 
      of Medical Sciences, School of Basic Medicine, Peking Union Medical College, 
      Beijing, 100005, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220101
PL  - Australia
TA  - Theranostics
JT  - Theranostics
JID - 101552395
RN  - 0 (CXCL12 protein, human)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (RNA, Neoplasm)
SB  - IM
MH  - *Cancer-Associated Fibroblasts/classification/metabolism
MH  - Cell Communication
MH  - Chemokine CXCL12/metabolism
MH  - Gastric Mucosa/pathology
MH  - Humans
MH  - RNA, Neoplasm
MH  - RNA-Seq
MH  - Single-Cell Analysis
MH  - Stomach Neoplasms/genetics/*pathology/therapy
MH  - Survival Rate
MH  - Treatment Outcome
MH  - Tumor Cells, Cultured
MH  - Tumor Microenvironment
PMC - PMC8692898
OTO - NOTNLM
OT  - CAF heterogeneity
OT  - Gastric cancer
OT  - Multistaining registration
OT  - Tumor microenvironment
OT  - eCAF
OT  - iCAF
OT  - scRNA-Seq
COIS- Competing Interests: The authors have declared that no competing interest exists.
EDAT- 2022/01/04 06:00
MHDA- 2022/03/11 06:00
PMCR- 2022/01/01
CRDT- 2022/01/03 05:40
PHST- 2021/03/17 00:00 [received]
PHST- 2021/11/05 00:00 [accepted]
PHST- 2022/01/03 05:40 [entrez]
PHST- 2022/01/04 06:00 [pubmed]
PHST- 2022/03/11 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - thnov12p0620 [pii]
AID - 10.7150/thno.60540 [doi]
PST - epublish
SO  - Theranostics. 2022 Jan 1;12(2):620-638. doi: 10.7150/thno.60540. eCollection 
      2022.