cDNA microarray analysis of serially sampled cervical cancer specimens from patients treated with thermochemoradiotherapy.
OBJECTIVE
To elucidate changes in gene expression after treatment with regional thermochemoradiotherapy in locally advanced squamous cell cervical cancer.


METHODS
Tru-Cut biopsy specimens were serially collected from 16 patients. Microarray gene expression levels before and 24 h after the first and second trimodality treatment sessions were compared. Pathway and network analyses were conducted by use of Ingenuity Pathways Analysis (IPA; Ingenuity Systems, Redwood City, CA). Single gene expressions were analyzed by quantitative real-time reverse transcription-polymerase chain reaction.


RESULTS
We detected 53 annotated genes that were differentially expressed after trimodality treatment. Central in the three top networks detected by IPA were interferon alfa, interferon beta, and interferon gamma receptor; nuclear factor kappaB; and tumor necrosis factor, respectively. These genes encode proteins that are important in regulation cell signaling, proliferation, gene expression, and immune stimulation. Biological processes over-represented among the 53 genes were fibrosis, tumorigenesis, and immune response.


CONCLUSIONS
Microarrays showed minor changes in gene expression after thermochemoradiotherapy in locally advanced cervical cancer. We detected 53 differentially expressed genes, mainly involved in fibrosis, tumorigenesis, and immune response. A limitation with the use of serial biopsy specimens was low quality of ribonucleic acid from tumors that respond to highly effective therapy. Another "key limitation" is timing of the post-treatment biopsy, because 24 h may be too late to adequately assess the impact of hyperthermia on gene expression.
Borkamo
Erling Dahl
ED
Section of Oncology, Institute of Medicine, University of Bergen, Bergen, Norway. borkamo@gmail.com
Schem
Baard-Christian
BC
Fluge
Øystein
Ø
Bruland
Ove
O
Dahl
Olav
O
Mella
Olav
O
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000628:therapy / Q000821:virology; D002584:Cervix Uteri / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy / Q000379:methods; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods; D016898:Interferon-alpha / Q000235:genetics; D016899:Interferon-beta / Q000235:genetics; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics*; D009664:Norway; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011879:Radiotherapy Dosage; D017471:Receptors, Interferon / Q000235:genetics; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy / Q000821:virology; D000096743:Interferon gamma Receptor
D000970:Antineoplastic Agents; D002945:Cisplatin; D016898:Interferon-alpha; D016899:Interferon-beta; D016328:NF-kappa B; D009363:Neoplasm Proteins; D017471:Receptors, Interferon; D014409:Tumor Necrosis Factor-alpha; D000096743:Interferon gamma Receptor