Peripheral blood gene expression of B7 and CD28 family members associated with tumor progression and microscopic lymphovascular invasion in colon cancer patients.
OBJECTIVE
To associate the global gene expression of B7/CD28 family transcripts with pathologic features of colon cancer, we determined the B7/CD28 family transcripts in peripheral blood mononuclear cells (PBMCs) from normal subjects and patients with adenomatous polyps and colon cancer, and correlated the results with pathologic features of colon cancer.


METHODS
PBMCs from age-matched normal subjects and patients with adenomatous polyps and colon cancer were analyzed for peripheral blood transcripts (PBTs) of B7/CD28 family using real-time PCR. Differences in expression levels of B7/CD28 PBTs across all cancer stages and between colon cancer patients with or without microscopic lymphovascular invasion (LVI) were analyzed.


RESULTS
The results showed a significant upregulation of PBTs of co-inhibitory molecules such as B7-H3 and PD-1 and a significant PBT downregulation of co-stimulatory molecules including CD28 and ICOS in colon cancer patients. Furthermore, the increase of B7-H3 PBT was strongly associated with tumor invasion (P = 0.025) and advanced TNM stages (P = 0.019), whereas the decline of co-stimulatory ligand B7-H2 PBT was related to regional lymph node metastasis (P = 0.028) and aggressive tumor invasion (P = 0.031). In addition, the ratios of PBT expression of CD28 family to B7 family such as CTLA-4 to B7-H2 and PD-1 to B7-H2 were significantly higher in colon cancer patients with microscopic LVI than in those without LVI (P = 0.001 and P = 0.016, respectively).


CONCLUSIONS
Our results suggest that B7/CD28 family PBTs may serve as valuable markers reflecting the pathological features of colon cancer.
Department of Microbiology and Immunology, Bio-Marker Research Center for Personalized Therapy, Inje University College of Medicine, Busan, 614-735, Korea.
Hyunji
H
Lee
Ji Hyun
JH
Kim
Sung Yeun
SY
Yang
Jihye
J
Kong
Minkyung
M
Oh
Dae Hoon
DH
Jeong
Jae-Il
JI
Chung
Ki Beom
KB
Bae
Jin Yong
JY
Shin
Kwan Hee
KH
Hong
Inhak
I
Choi
D000368:Aged; D018122:B7-1 Antigen / Q000097:blood / Q000235:genetics*; D018106:CD28 Antigens / Q000097:blood / Q000235:genetics*; D003110:Colonic Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D008297:Male; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000235:genetics
D018122:B7-1 Antigen; D018106:CD28 Antigens