title: Microarray analysis reveals that high mobility group A1 is involved in colorectal cancer metastasis.
abstract: Tumor size indicates the extent of cell proliferation in most cases of colorectal cancer (CRC), although there are some advanced small tumors with metastases. Lymph node metastasis is a significant factor that greatly impacts disease prognosis in CRC cases. The underlying factors that cause lymph node metastasis in CRC cells are not fully understood. We investigated the mechanism that might induce CRC metastasis by focusing on smaller sized (<2 cm) invasive tumors. We carried out gene expression array analysis for CRC cases; group 1 consisted of 6 cases with tumors <2 cm with metastases, and group 2 consisted of 65 cases with tumors >2 cm without metastases. Results were validated using gene expression array data from an additional 77 cases and another bulk case set of 172 cases. Gene ontology and pathway analysis using microarray data revealed that anti-apoptotic activity had a crucial role in CRC metastasis. High mobility group A1 (HMGA1) was identified as a biomarker for poor prognosis and metastasis formation. HMGA1 expression levels were higher in lymph node-positive cases than in lymph node-negative cases, even in subgroup analysis of submucosal invasive cases. The present study strongly supports the clinical significance of HMGA1 expression as a predictive indicator of lymph node metastasis in CRC cases, even in submucosal invasive cases which could be cured by local resection.
authors.affiliation: Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Genta
authors.initials: G
authors.lastname: Sawada
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Sato
authors.forename: Junji
authors.initials: J
authors.lastname: Kurashige
authors.forename: Kosuke
authors.initials: K
authors.lastname: Mima
authors.forename: Tae
authors.initials: T
authors.lastname: Matsumura
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Uchi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ueo
authors.forename: Masahisa
authors.initials: M
authors.lastname: Ishibashi
authors.forename: Yuki
authors.initials: Y
authors.lastname: Takano
authors.forename: Sayuri
authors.initials: S
authors.lastname: Akiyoshi
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Eguchi
authors.forename: Tomoya
authors.initials: T
authors.lastname: Sudo
authors.forename: Keishi
authors.initials: K
authors.lastname: Sugimachi
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Tanaka
authors.forename: Shin-Ei
authors.initials: SE
authors.lastname: Kudo
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Doki
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
authors.forename: Koshi
authors.initials: K
authors.lastname: Mimori
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D063990:Gene Ontology; D025741:HMGA1a Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D061346:Laser Capture Microdissection; D008113:Liver Neoplasms / Q000235:genetics / Q000401:mortality / Q000556:secondary*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D010534:Peritoneal Neoplasms / Q000235:genetics / Q000401:mortality / Q000556:secondary*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D025741:HMGA1a Protein