Co-expression patterns of tumor-associated antigen genes by non-small cell lung carcinomas: implications for immunotherapy.
BACKGROUND
Polyvalent vaccination represents a recent attempt to improve the effectiveness of lung cancer immunotherapy. This study aimed to investigate whether a gene expression pattern of tumor-associated antigens (TAA) would exist indicating that their use will be most appropriate for the polyvalent vaccination of Caucasian non-small cell lung carcinoma (NSCLC) patients. We examined the concomitant expression of genes belonging to different TAA families for which expression frequencies either have never been detected in NSCLC or vary widely in the literature.


RESULTS
15/23 (65%) and 8/23 (35%) tumor samples were found expressing 6-11 and 2-5 out of the 12 examined TAAs, respectively, at levels >1% of the testis reference sample. The most prevalent TAA patterns observed were those of survivin standard (survivin-std)/survivin-2B expressed by 22/23 (95.5%) tumor samples and of survivin-std/survivin-2B/hTERT expressed by 19/23 (82.5%) tumor samples. The expression levels of the survivin-std gene strongly positively correlated to those of the survivin-2B (p=0.001) and the hTERT genes (p=0.031). The number of concomitantly expressed genes was found to be positively correlated to the age of the patients (p=0.001) and the tumor size (p=0.048).


METHODS
Tumor material from 23 patients with NSCLC (12 adenocarcinomas, 8 squamous cell carcinomas, 3 bronchiolo-carcinomas) was examined. mRNA transcripts were detected for 5 genes of the survivin family, 5 MAGE-A genes as well as the genes of human telomerase reverse transcriptase (hTERT) and p53, by the use of quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR) or semi-quantitative RT-PCR.


CONCLUSIONS
This study provides evidence that, in Caucasian patients with NSCLC, highly prevalent expression patterns of TAA genes, predominantly of overexpressed TAAs, do exist. This result implies that the combined use of these TAA could help in designing more effective NSCLC immunotherapeutic protocols.
Karanikas
Vaios
V
Cancer Immunology Unit, Department of Immunology and Histocompatibility, School of Medicine, University of Thessaly, University Hospital of Larissa, Greece. vkaran@med.uth.gr
Tsochas
Stefanos
S
Boukas
Konstantinos
K
Kerenidi
Theodora
T
Nakou
Marianna
M
Dahabreh
Jubrail
J
Poularakis
Theodoros
T
Gourgoulianis
Konstantinos I
KI
Germenis
Anastasios E
AE
D000199:Actins / Q000235:genetics; D000951:Antigens, Neoplasm / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D017931:DNA Primers; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D051034:Inhibitor of Apoptosis Proteins; D008175:Lung Neoplasms / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D009367:Neoplasm Staging; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin; D019098:Telomerase / Q000235:genetics
D000199:Actins; D000951:Antigens, Neoplasm; C107489:BIRC5 protein, human; D017931:DNA Primers; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; D019098:Telomerase