Cancer Microarray, Genes and Proteins Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India.
Int J Gynecol Cancer. 2013 May;23(4):650-8. doi: 10.1097/IGC.0b013e31828a0698.
Cervical cancer is one of the major gynecologic cancers. In developing countries, because of a lack of medical support and infrastructure, cervical cancer is the leading cause of cancer-related deaths. Therefore, there is a need to identify novel biomarkers for cervical cancers. In this context, cancer-testis (CT) antigens represent a unique class of tumor antigens that have been shown to be associated with various solid tumors. These antigens have restricted expression in testis and no expression in somatic tissues. Because of their restricted expression, CT antigens are novel candidate molecules for early detection and diagnosis and immunotherapy. In the present study, novel CT antigen A-kinase anchor protein 4 (AKAP4) expression and humoral response were investigated in patients with cervical cancer.
In this study, 74 cervical cancer tissue specimens, which included different tumor stages (stage I [n = 35], stage II [n = 39]) and histologic grades (grade 1 [n = 17], grade 2 [n = 46], and grade 3[n = 11]) and 62 adjacent noncancerous tissue specimens were investigated for AKAP4 gene expression by using reverse transcriptase polymerase chain reaction and in situ RNA hybridization. Furthermore, AKAP4 protein expression was determined by immunohistochemistry. In addition, humoral response against purified recombinant AKAP4 protein was determined in available sera of 70 patients with cervical cancer by enzyme-linked immuno assay (ELISA).
Our study revealed that AKAP4 gene and protein expression was detected in 86% of total patients with cervical cancer. Based on the AKAP4 immunoreactivity score, most of stage I (n = 22/29) and stage II (n = 30/35) specimens revealed high AKAP4 expression (≥50% AKAP4-positive cells). A-kinase anchor protein 4 expression was significantly associated with early grades tumor specimens (P = 0.023). In addition, humoral response was detected in 53% of patients irrespective of stages, lymph node positivity, and grades.
Collectively, our data indicate the putative role of AKAP4 in early tumorigenesis and may be implicated as a biomarker and immunotherapeutic target for cervical cancer.
宫颈癌是妇科癌症中的一种。在发展中国家，由于医疗支持和基础设施的缺乏，宫颈癌是癌症相关死亡的主要原因。因此，需要确定新的宫颈癌生物标志物。在这种情况下，癌睾丸抗原（CT）抗原代表了一类独特的肿瘤抗原，这些抗原与各种实体瘤有关。这些抗原在睾丸中特异性表达，在体细胞中不表达。由于其表达受限，CT 抗原是早期检测、诊断和免疫治疗的新候选分子。在本研究中，我们研究了宫颈癌患者中新型 CT 抗原 A-激酶锚蛋白 4（AKAP4）的表达和体液反应。
在这项研究中，通过逆转录聚合酶链反应和原位 RNA 杂交，对 74 例宫颈癌组织标本（包括不同的肿瘤分期（Ⅰ期[35 例]、Ⅱ期[39 例]）和组织学分级（Ⅰ级[17 例]、Ⅱ级[46 例]和Ⅲ级[11 例]）和 62 例相邻非癌组织标本进行 AKAP4 基因表达研究。此外，通过免疫组织化学法测定 AKAP4 蛋白表达。此外，通过酶联免疫吸附试验（ELISA）测定 70 例宫颈癌患者的血清中针对纯化重组 AKAP4 蛋白的体液反应。
我们的研究表明，AKAP4 基因和蛋白表达在 86%的宫颈癌患者中均被检测到。根据 AKAP4 免疫反应评分，大多数Ⅰ期（n=22/29）和Ⅱ期（n=30/35）标本显示 AKAP4 高表达（≥50%AKAP4 阳性细胞）。AKAP4 表达与早期分级肿瘤标本显著相关（P=0.023）。此外，53%的患者无论分期、淋巴结阳性或分级均检测到体液反应。
总之，我们的数据表明 AKAP4 在早期肿瘤发生中的潜在作用，并可能作为宫颈癌的生物标志物和免疫治疗靶点。
