title: High level of Nm23-H1 gene expression is associated with local colorectal cancer progression not with metastases.
abstract: This study aimed to determine the expression of Nm23-H1 in colorectal cancer and liver metastases and to correlate Nm23-H1 expression with clinicopathological variables. Specimens from 59 primary colorectal cancers and five liver metastases were studied using Northern blot hybridisation. The mean +/- s.e. of tumour/normal (T/N) ratio of Nm23-H1 RNA expression was 4.3 +/- 0.4 (P < 0.001) and 5.1 +/- 0.90 (P < 0.01) for colorectal cancer and liver metastases respectively. No significant relationship was observed between the level of Nm23-H1 RNA and the patient's age, sex, tumour location, differentiation, presence of lymph node involvement or distant metastases. Nm23-H1 RNA level was 2.6 +/- 0.5 for tumour size less than 3.0 cm and 4.6 +/- 0.5 for those > or = 3.0 cm (P = 0.05). There appeared to be a trend between increasing relative Nm23-H1 RNA and bowel wall invasion, irrespective of metastatic status (T1 = 1.9 +/- 0.3, T2 = 4.1 +/- 0.6, T3 = 4.1 +/- 0.5 and T4 = 6.4 +/- 1.6). This difference was statistically significant when T1 was compared against > or = T2 lesions (P = 0.01). Western blot analysis reveals two Nm23H-1 bands (17.0 kDa and 18.5 kDa). In 16 colorectal patients, the T/N fold-increase in protein expression was 2.66 +/- 0.46 (P < 0.001) and 2.40 +/- 0.32 (P < 0.001) for the 17.0 and 18.5 kDa band respectively. Both Nm23-H1 RNA and protein levels in primary colorectal cancers do not appear to correlate with synchronous regional or distant metastases. Since Nm23-H1 RNA expression is associated with increasing tumour size and tumour local invasion, Nm23-H1 RNA expression may be associated with local disease progression.
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
authors.forename: Z S
authors.initials: ZS
authors.lastname: Zeng
authors.forename: S
authors.initials: S
authors.lastname: Hsu
authors.forename: Z F
authors.initials: ZF
authors.lastname: Zhang
authors.forename: A M
authors.initials: AM
authors.lastname: Cohen
authors.forename: W E
authors.initials: WE
authors.lastname: Enker
authors.forename: A A
authors.initials: AA
authors.lastname: Turnbull
authors.forename: J G
authors.initials: JG
authors.lastname: Guillem
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015152:Blotting, Northern; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D020559:Monomeric GTP-Binding Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D009361:Neoplasm Invasiveness; D009701:Nucleoside-Diphosphate Kinase; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
chemical_list: D054778:NM23 Nucleoside Diphosphate Kinases; D012334:RNA, Neoplasm; D014157:Transcription Factors; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins