title: Interleukin-10 haplotype may predict survival and relapse in resected non-small cell lung cancer.
abstract: IL-10 is associated with tumor malignancy via immune escape. We hypothesized that IL-10 haplotypes categorized by IL-10 promoter polymorphisms at -1082A>G, -819C>T, and -592C>A might influence IL-10 expression and give rise to non-small cell lung cancer (NSCLC) patients with poor outcomes and relapse. We collected adjacent normal tissues from 385 NSCLC patients to determine IL-10 haplotypes by direct sequencing and polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Of the 385 tumors, 241 were available to evaluate IL-10 mRNA expression levels by real-time RT-PCR. The influence of IL-10 haplotypes on overall survival (OS) and relapse free survival (RFS) were determined by Kaplan-Meier and multivariate Cox regression analysis. The results showed that IL-10 mRNA levels were significantly higher in tumors with the non-ATA haplotype than with the ATA haplotype (P = 0.004). Patients with the non-ATA haplotype had shorter OS and RFS periods than did patients with the ATA haplotype. This may be associated with the observation that the number of tumor-infiltrating lymphocytes was decreased in the tumors with higher levels of IL-10. Consistently, T cells from the peripheral blood of the patients with non-ATA haplotype were more susceptible to apoptosis and less cytotoxic to tumor cells, compared to those from the patients with ATA haplotype. The results suggest that IL-10 can promote tumor malignancy via promoting T cell apoptosis and tumor cell survival, and IL-10 haplotype evaluated by PCR-RFLP or direct sequencing may be used to predict survival and relapse in resected NSCLC, helping clinicians to make appropriate decisions on treatment of the patients.
authors: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan, ROC.
authors: Yaw-Cheng
authors: YC
authors: Wang
authors: Wen-Wei
authors: WW
authors: Sung
authors: Tzu-Chin
authors: TC
authors: Wu
authors: Lee
authors: L
authors: Wang
authors: Wen-Pin
authors: WP
authors: Chien
authors: Ya-Wen
authors: YW
authors: Cheng
authors: Chih-Yi
authors: CY
authors: Chen
authors: Shwn-Huey
authors: SH
authors: Shieh
authors: Huei
authors: H
authors: Lee
mesh_terms: D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000276:immunology / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D005260:Female; D006239:Haplotypes; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics* / Q000276:immunology; D008175:Lung Neoplasms / Q000235:genetics* / Q000276:immunology / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D008297:Male; D051379:Mice; D008875:Middle Aged; D009374:Neoplasms, Experimental / Q000235:genetics / Q000276:immunology / Q000473:pathology; D012150:Polymorphism, Restriction Fragment Length; D011401:Promoter Regions, Genetic; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D019139:Tumor Escape / Q000235:genetics
chemical_list: C508609:IL10 protein, human; C556062:IL10 protein, mouse; D016753:Interleukin-10