PMID- 35894836
OWN - NLM
STAT- MEDLINE
DCOM- 20230224
LR  - 20230226
IS  - 2045-7634 (Electronic)
IS  - 2045-7634 (Linking)
VI  - 12
IP  - 3
DP  - 2023 Feb
TI  - The structural maintenance of chromosomes 5 is a possible biomarker for 
      individualized treatment of colorectal cancer.
PG  - 3276-3287
LID - 10.1002/cam4.5074 [doi]
AB  - BACKGROUND: Although the understanding of resistance to oxaliplatin (OXA) 
      chemotherapy in colorectal cancer (CRC) has been sought for many years, drug 
      tolerance remains a major challenge for cancer therapy. Revealing the molecular 
      mechanism of OXA resistance could help to explain the poor prognosis of patients. 
      METHODS: Gene expression omnibus (GEO) database was searched, GSE83129, which 
      contains RNA profiling in metastatic CRC patients treated first-line with OXA, 
      was chosen for the following analysis. Differential expressed genes (DEGs) 
      between the adenocarcinoma and adjacent_normal team, respectively, in the OXA 
      responders and no-responders were analyzed. The Gene Ontology (GO) and hub genes 
      in the protein-protein interaction (PPI) network were used for the molecular 
      mechanism of OXA resistance. Tumor-related databases were used for the clinical 
      relevance of the structural maintenance of chromosomes 5 (SMC5) in CRC. The in 
      vitro assays were used to detect the molecular function of SMC5 in CRC cells. 
      Quantitative real-time PCR (qRT-PCR) and western blot were used to detect the 
      expression of the structural maintenance of chromosomes 5/6 (SMC5/6) complex 
      components upon OXA and raltitrexed (RTX) treatment. CCK-8 was used to detect the 
      cell viability of cells with different treatment. RESULTS: SMC5 was downregulated 
      in CRC tissues of OXA no-response patients. Lower expression of SMC5 was 
      correlated with a poor prognosis in CRC patients, improved this gene expression, 
      inhibited the CRC cell growth and invasion in vitro. Furthermore, SMC5 was 
      downregulated upon OXA treatment in CRC cells, while RTX would reverse its 
      expression, and the combination of these two drugs restored the SMC5 level to the 
      normal situation. Finally, RTX treatment enhanced the OXA cytotoxicity. 
      CONCLUSION: SMC5 is a tumor suppressor, that low expression of this gene is 
      benefit for the development of CRC. Combination treatment with RTX and OXA may be 
      more suitable for those OXA no-responders with lower SMC5.
CI  - (c) 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
FAU - Gong, Xiaoxia
AU  - Gong X
AD  - School of Life Science and Technology, MOE Key Laboratory of Developmental Genes 
      and Human Diseases, Southeast University, Nanjing, China.
FAU - Tian, Xiaowei
AU  - Tian X
AD  - General Surgery Department, Qingdao Municipal Hospital affiliated to Qingdao 
      University, Qingdao, China.
FAU - Xie, Hao
AU  - Xie H
AUID- ORCID: 0000-0002-0683-6883
AD  - School of Life Science and Technology, MOE Key Laboratory of Developmental Genes 
      and Human Diseases, Southeast University, Nanjing, China.
FAU - Li, Zhaoshui
AU  - Li Z
AD  - Qingdao Medical College, Qingdao University, Qingdao, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220727
PL  - United States
TA  - Cancer Med
JT  - Cancer medicine
JID - 101595310
RN  - 0 (Biomarkers)
RN  - 04ZR38536J (Oxaliplatin)
RN  - 0 (SMC5 protein, human)
RN  - 0 (Chromosomal Proteins, Non-Histone)
RN  - 0 (Cell Cycle Proteins)
RN  - FCB9EGG971 (raltitrexed)
SB  - IM
MH  - Humans
MH  - Biomarkers
MH  - *Colorectal Neoplasms/diagnosis/genetics
MH  - Gene Expression Regulation, Neoplastic
MH  - Genes, Tumor Suppressor
MH  - Oxaliplatin/pharmacology
MH  - *Chromosomal Proteins, Non-Histone/genetics
MH  - *Cell Cycle Proteins/genetics
PMC - PMC9939147
OTO - NOTNLM
OT  - SMC5
OT  - biomarker
OT  - oxaliplatin
OT  - raltitrexed
OT  - tumor suppressor
COIS- The authors report no conflicts of interest for this work.
EDAT- 2022/07/28 06:00
MHDA- 2023/02/25 06:00
PMCR- 2022/07/27
CRDT- 2022/07/27 10:32
PHST- 2022/06/16 00:00 [revised]
PHST- 2022/02/18 00:00 [received]
PHST- 2022/07/03 00:00 [accepted]
PHST- 2022/07/28 06:00 [pubmed]
PHST- 2023/02/25 06:00 [medline]
PHST- 2022/07/27 10:32 [entrez]
PHST- 2022/07/27 00:00 [pmc-release]
AID - CAM45074 [pii]
AID - 10.1002/cam4.5074 [doi]
PST - ppublish
SO  - Cancer Med. 2023 Feb;12(3):3276-3287. doi: 10.1002/cam4.5074. Epub 2022 Jul 27.