title: Absence of gamma-interferon-inducible lysosomal thiol reductase (GILT) is associated with poor disease-free survival in breast cancer patients.
abstract: Tumor immunosurveillance is known to be of critical importance in controlling tumorigenesis and progression in various cancers. The role of gamma-interferon-inducible lysosomal thiol reductase (GILT) in tumor immunosurveillance has recently been studied in several malignant diseases, but its role in breast cancer remains to be elucidated. In the present study, we found GILT as a significant different expressed gene by cDNA microarray analysis. To further determine the role of GILT in breast cancer, we examined GILT expression in breast cancers as well as noncancerous breast tissues by immunohistochemistry and real-time PCR, and assessed its association with clinicopathologic characteristics and patient outcome. The absence of GILT expression increased significantly from 2.02% (2/99) in noncancerous breast tissues to 15.6% (34/218) in breast cancer tissues (P<0.001). In accordance with its proliferation inhibiting function, GILT expression was inversely correlated with Ki67 index (P<0.05). In addition, absence of GILT was positively correlated with adverse characteristics of breast cancers, such as histological type, tumor size, lymph nodes status, and pTNM stage (P<0.05). Consistently, breast cancers with reduced GILT expression had poorer disease-free survival (P<0.005). Moreover, significantly decreased expression of GILT was found in both primary and metastatic breast cancer cells, in contrast to normal epithelial cells. These findings indicate that GILT may act as a tumor suppressor in breast cancer, in line with its previously suggested role in anti-tumor immunity. Thus, GILT has the potential to be a novel independent prognostic factor in breast cancer and further studies are needed to illustrate the underlying mechanism of this relationship.
authors.affiliation: Department of Breast Surgery, The Second Hospital of Shandong University, Jinan, Shandong province, People's Republic of China.
authors.forename: Yu-Juan
authors.initials: YJ
authors.lastname: Xiang
authors.affiliation: Department of Breast Surgery, The Second Hospital of Shandong University, Jinan, Shandong province, People's Republic of China.
authors.forename: Ming-Ming
authors.initials: MM
authors.lastname: Guo
authors.affiliation: Department of Pathology, The Second Hospital of Shandong University, Jinan, Shandong province, People's Republic of China.
authors.forename: Cheng-Jun
authors.initials: CJ
authors.lastname: Zhou
authors.affiliation: Department of Breast Surgery, The Second Hospital of Shandong University, Jinan, Shandong province, People's Republic of China.
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Pathology, Shandong University Medical School, Jinan, Shandong province, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Han
authors.affiliation: Department of Breast Diseases, Linyi Tumor Hospital, Linyi, Shandong province, People's Republic of China.
authors.forename: Ling-Yu
authors.initials: LY
authors.lastname: Kong
authors.affiliation: Department of General Surgery, Linyi People's Hospital, Linyi, Shandong province, People's Republic of China.
authors.forename: Zhong-Cheng
authors.initials: ZC
authors.lastname: Gao
authors.affiliation: Department of Breast Surgery, The Second Hospital of Shandong University, Jinan, Shandong province, People's Republic of China.
authors.forename: Zhong-Bing
authors.initials: ZB
authors.lastname: Ma
authors.affiliation: Division of Epidemiology and Biostatistics, School of Public Health, Shandong University, Jinan, Shandong province, People's Republic of China.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pathology, Affiliated Hospital of Shandong Academy of Medical Sciences, Jinan, Shandong province, People's Republic of China.
authors.forename: Man
authors.initials: M
authors.lastname: Feng
authors.affiliation: Oral Maxillofacial-Head and Neck Key Laboratory of Medical Biology, and Central Laboratory for Experimental Medicine, Liaocheng People's Hospital, Liaocheng, Shandong province, People's Republic of China.
authors.forename: Hai-Ying
authors.initials: HY
authors.lastname: Chen
authors.affiliation: Department of Pathology, Liaocheng People's Hospital, Liaocheng, Shandong province, People's Republic of China.
authors.forename: Guo-Tao
authors.initials: GT
authors.lastname: Jia
authors.affiliation: Department of Breast Surgery, The Second Hospital of Shandong University, Jinan, Shandong province, People's Republic of China.
authors.forename: De-Zong
authors.initials: DZ
authors.lastname: Gao
authors.affiliation: Department of Breast Surgery, The Second Hospital of Shandong University, Jinan, Shandong province, People's Republic of China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Breast Surgery, The Second Hospital of Shandong University, Jinan, Shandong province, People's Republic of China.
authors.forename: Liang
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Breast Surgery, The Second Hospital of Shandong University, Jinan, Shandong province, People's Republic of China.
authors.forename: Yu-Yang
authors.initials: YY
authors.lastname: Li
authors.affiliation: Department of Breast Surgery, The Second Hospital of Shandong University, Jinan, Shandong province, People's Republic of China.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Yu
mesh_terms: D000328:Adult; D000368:Aged; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D016019:Survival Analysis; D059467:Transcriptome
chemical_list: D019394:Ki-67 Antigen; D012333:RNA, Messenger; C056859:IFI30 protein, human; D050862:Oxidoreductases Acting on Sulfur Group Donors