TY - JOUR
T1 - The Debated Issue on Tissue Copper Levels in Colorectal Cancer Patients: A Meta-analysis and Replication Study
AU - Squitti, Rosanna
AU - Pal, Amit
AU - Dhar, Aninda
AU - Shamim, Muhammad Aaqib
AU - Goswami, Kalyan
AU - De Luca, Anastasia
AU - Rizzo, Gianluca
AU - Rongioletti, Mauro
AU - Tondolo, Vincenzo
PY - 2024
Y1 - 2024
N2 - Colorectal cancer (CRC) is a growing public health problem. Several clinical studies have shown a potentially oncogenic role of copper in CRC progression, but the reports are inconsistent. To examine published evidence on the association between tissue copper status and CRC, we carried out a systematic review and meta-analysis, searching Cochrane Library, EBSCOhost, Embase, ProQuest, PubMed/Medline, Scopus, and Web of Science for studies reporting colon tumor and matched non-cancerous tissue copper concentrations in CRC patients for articles published till June 2023. Based on a random effects model, standardized mean differences (SMD) were assessed. We also completed a replication study on 17 CRC patients that analyzed copper levels in both cancer tissue specimens and healthy mucosa dissected from the same patient. Thirteen studies investigating copper levels (including the replication study) in colorectal specimens from a pooled total of 312 CRC and 298 healthy mucosa were selected. Our meta-analysis estimated a high between-study heterogeneity (I2 = 96%) and lower levels of copper in CRC tissue cancer specimens than in matched healthy mucosa: the decrease was equal to − 0.74 (95% CI, − 2.18; 0.71) but was not significant. The replication study showed a significant decrease in tissue cancer specimens. Sensitivity analyses of the meta-analysis revealed that pre-analytical methodology for tissue preparation significantly reduced the between-study heterogeneity strongly influencing copper levels (p < 0.01), indicating a copper decrease in the cytoplasmic copper pool of the tumor tissue suggesting a rapid turnover of the metal in cancer cells.
AB - Colorectal cancer (CRC) is a growing public health problem. Several clinical studies have shown a potentially oncogenic role of copper in CRC progression, but the reports are inconsistent. To examine published evidence on the association between tissue copper status and CRC, we carried out a systematic review and meta-analysis, searching Cochrane Library, EBSCOhost, Embase, ProQuest, PubMed/Medline, Scopus, and Web of Science for studies reporting colon tumor and matched non-cancerous tissue copper concentrations in CRC patients for articles published till June 2023. Based on a random effects model, standardized mean differences (SMD) were assessed. We also completed a replication study on 17 CRC patients that analyzed copper levels in both cancer tissue specimens and healthy mucosa dissected from the same patient. Thirteen studies investigating copper levels (including the replication study) in colorectal specimens from a pooled total of 312 CRC and 298 healthy mucosa were selected. Our meta-analysis estimated a high between-study heterogeneity (I2 = 96%) and lower levels of copper in CRC tissue cancer specimens than in matched healthy mucosa: the decrease was equal to − 0.74 (95% CI, − 2.18; 0.71) but was not significant. The replication study showed a significant decrease in tissue cancer specimens. Sensitivity analyses of the meta-analysis revealed that pre-analytical methodology for tissue preparation significantly reduced the between-study heterogeneity strongly influencing copper levels (p < 0.01), indicating a copper decrease in the cytoplasmic copper pool of the tumor tissue suggesting a rapid turnover of the metal in cancer cells.
KW - Colorectal cancer
KW - Copper
KW - Systematic Reviews and Meta-Analysis
KW - Specimens
KW - Replication
KW - Colorectal cancer
KW - Copper
KW - Systematic Reviews and Meta-Analysis
KW - Specimens
KW - Replication
UR - http://hdl.handle.net/10807/305196
U2 - 10.1007/s12011-024-04421-z
DO - 10.1007/s12011-024-04421-z
M3 - Article
SN - 0163-4984
SP - N/A-N/A
JO - Biological Trace Element Research
JF - Biological Trace Element Research
ER -