PMID- 36267705
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221022
IS  - 2305-5839 (Print)
IS  - 2305-5847 (Electronic)
IS  - 2305-5839 (Linking)
VI  - 10
IP  - 18
DP  - 2022 Sep
TI  - Identification of key genes and pathway related to chemoresistance of small cell 
      lung cancer through an integrative bioinformatics analysis.
PG  - 968
LID - 10.21037/atm-22-3642 [doi]
LID - 968
AB  - BACKGROUND: Small cell lung cancer (SCLC), the most malignant of all the lung 
      cancer subtypes, is characterized by drug resistance. This study sought to 
      explore the key genes and pathways associated with the chemoresistance of SCLC. 
      METHODS: The drug sensitivity of chemosensitive and chemoresistance SCLC cell 
      lines was measured by Cell Counting Kit-8 assays. The total RNA from 
      chemosensitive cell line H69 and chemoresistance cell line H69AR cells was 
      extracted and subjected to messenger RNA (mRNA) and long non-coding RNA (lncRNA) 
      microarray analyses. The differentially expressed genes (DEGs) and the 
      differentially expressed lncRNAs (DELs) were screened out with a threshold of a 
      |log fold change | >/=1 and an adjusted P value <0.05. A protein-protein 
      interaction network was constructed, and hub genes were screened out. A 
      lncRNA-mRNA co-expression network was also constructed. Gene Ontology and Kyoto 
      Encyclopedia of Genes, Genomes enrichment analyses and Cis-regulatory element 
      analyses were conducted on the DEGs and the top 10 upregulated DEL-co-expressed 
      DEGs. The expression of the key genes was further analyzed in the GSE149507 data 
      set and validated in H69/H69AR and H446/H446DDP cells by quantitative polymerase 
      chain reaction assays. RESULTS: The microarray results showed that a total of 609 
      mRNAs and 394 lncRNAs were differentially expressed in the chemoresistant SCLC 
      cells. The mammalian target of rapamycin (mTOR) signaling pathway was enriched 
      among the DEGs, the top 10 upregulated DEL-co-expressed DEGs, and the 
      NCRNA00173-co-expressed DEGs, which included IGF1, INS, WNT6, WNT11, WNT2B, and 
      SESN2. IGF1, WNT2B, and SESN2 were downregulated, and WNT11 was upregulated in 
      the SCLC tumor tissues in the GSE149507 data set. Further, IGF1, WNT6, WNT11, and 
      WNT2B were lowlier expressed and SESN2 and NCRNA00173 were more highly expressed 
      in the chemoresistant cells than sensitive cells. CONCLUSIONS: The top 10 
      upregulated DELs containing NCRNA00173 may be involved in the regulation of drug 
      resistance in SCLC. These DELs may regulate the genes related to the mTOR 
      signaling pathway. These genes may also be biomarkers and potential targets for 
      the treatment of SCLC.
CI  - 2022 Annals of Translational Medicine. All rights reserved.
FAU - Zeng, Fan-Rui
AU  - Zeng FR
AD  - Department of Radiation Oncology, The First Affiliated Hospital of Guangzhou 
      Medical University, Guangzhou, China.
FAU - Zhou, Xu-Yang
AU  - Zhou XY
AD  - Department of Pathology, Zhujiang Hospital, Southern Medical University, 
      Guangzhou, China.
FAU - Zeng, Ling-Ge
AU  - Zeng LG
AD  - Department of Pathology, Zhujiang Hospital, Southern Medical University, 
      Guangzhou, China.
FAU - Sun, Jian-Cong
AU  - Sun JC
AD  - Department of Radiation Oncology, The First Affiliated Hospital of Guangzhou 
      Medical University, Guangzhou, China.
FAU - He, Fen
AU  - He F
AD  - Department of Radiation Oncology, The First Affiliated Hospital of Guangzhou 
      Medical University, Guangzhou, China.
FAU - Mo, Wei
AU  - Mo W
AD  - Department of Radiation Oncology, The First Affiliated Hospital of Guangzhou 
      Medical University, Guangzhou, China.
FAU - Wen, Yang
AU  - Wen Y
AD  - Department of Pathology, Zhujiang Hospital, Southern Medical University, 
      Guangzhou, China.
FAU - Wang, Shu-Yu
AU  - Wang SY
AD  - Department of Pathology, Zhujiang Hospital, Southern Medical University, 
      Guangzhou, China.
FAU - Liu, Qin
AU  - Liu Q
AD  - Department of Radiology, The First Affiliated Hospital of Guangzhou Medical 
      University, Guangzhou, China.
FAU - Guo, Lin-Lang
AU  - Guo LL
AD  - Department of Pathology, Zhujiang Hospital, Southern Medical University, 
      Guangzhou, China.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Ann Transl Med
JT  - Annals of translational medicine
JID - 101617978
PMC - PMC9577795
OTO - NOTNLM
OT  - Small cell lung cancer (SCLC)
OT  - chemoresistance
OT  - long non-coding RNA (lncRNA)
OT  - mTOR pathway
OT  - microarray analysis
COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure 
      form (available at 
      https://atm.amegroups.com/article/view/10.21037/atm-22-3642/coif). All authors 
      report that this work was supported by the National Natural Science Foundation of 
      China (No. 81902311), the Natural Science Foundation of Guangdong Province (No. 
      2020A1515011454), the Project of the Featured Clinical Technique of Guangzhou 
      (No. 2019TS28), and the Characteristic Innovation Project of Guangdong 
      Universities (Natural Science) (No. 2021KTSCX093). The authors have no other 
      conflicts of interest to declare.
EDAT- 2022/10/22 06:00
MHDA- 2022/10/22 06:01
PMCR- 2022/09/01
CRDT- 2022/10/21 03:00
PHST- 2022/07/04 00:00 [received]
PHST- 2022/08/18 00:00 [accepted]
PHST- 2022/10/21 03:00 [entrez]
PHST- 2022/10/22 06:00 [pubmed]
PHST- 2022/10/22 06:01 [medline]
PHST- 2022/09/01 00:00 [pmc-release]
AID - atm-10-18-968 [pii]
AID - 10.21037/atm-22-3642 [doi]
PST - ppublish
SO  - Ann Transl Med. 2022 Sep;10(18):968. doi: 10.21037/atm-22-3642.