Altered expression profiles of clock genes hPer1 and hPer2 in peripheral blood mononuclear cells of cancer patients undergoing surgery.
Patients undergoing surgery often develop symptoms of circadian rhythm disorders such as insomnia or delirium. However, the effect of surgery on the biological clock remains unknown. The present study examines the expression of clock genes in peripheral blood mononuclear cells (PBMCs) and measures plasma hormone concentrations in patients with esophageal cancer and early gastric cancer who underwent surgery. Six blood samples per day were collected from 9 patients with esophageal cancer before and after esophagectomy and from 9 patients with early gastric cancer before and after laparoscopy-assisted distal gastrectomy (LADG). The expression profiles of hPer1 and hPer2 mRNAs in PBMCs were determined by real-time RT-PCR. Plasma melatonin and cortisol concentrations were measured by radioimmunoassay. Plasma melatonin levels decreased in both groups throughout the day and plasma cortisol levels changed after surgery. The acrophase of clock gene expression was altered after surgery as follows: hPer1, from 6:19+/-1:50 to 13:59+/-0:59 (p=0.0003) and from 7:47+/-1:27 to 12:33+/-1:30 (p=0.0043) and hPer2, from 5:01+/-2:59 to 19:30+/-2:15 (p<0.0001) and from 6:49+/-1:59 to 13:39+/-3:06 (p=0.0171) in patients with esophageal and early gastric cancer, respectively. The post-operative phase change of hPer2 was more prominent after esophagectomy than after LADG. Our results suggest that surgical stress affects the peripheral clock as well as endogenous hormones in humans.
Azama
Takashi
T
Department of Surgery and Clinical Oncology, Graduate School of Medicine, Osaka University, Yamadaoka 2-2, Suita City, Osaka 565-0871, Osaka, Japan.
Yano
Masahiko
M
Oishi
Katsutaka
K
Kadota
Koji
K
Hyun
Kija
K
Tokura
Hiromi
H
Nishimura
Shinya
S
Matsunaga
Takashi
T
Iwanaga
Hiroshi
H
Miki
Hirofumi
H
Okada
Kazuyuki
K
Hiraoka
Nobuaki
N
Miyata
Hiroshi
H
Takiguchi
Shuji
S
Fujiwara
Yoshiyuki
Y
Yasuda
Takushi
T
Ishida
Norio
N
Monden
Morito
M
D018797:Cell Cycle Proteins / Q000235:genetics*; D002940:Circadian Rhythm / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000097:blood / Q000235:genetics / Q000601:surgery; D004946:Esophagostomy; D005743:Gastrectomy; D015870:Gene Expression; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008550:Melatonin / Q000097:blood; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D056950:Period Circadian Proteins; D013274:Stomach Neoplasms / Q000097:blood / Q000235:genetics / Q000601:surgery; D014157:Transcription Factors / Q000235:genetics*
D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; C539022:PER1 protein, human; C421902:PER2 protein, human; D056950:Period Circadian Proteins; D014157:Transcription Factors; D008550:Melatonin; D006854:Hydrocortisone