ZDHHC14基因在人舌鳞癌中的异常表达

Takeshi Onda, Nobuharu Yamamoto, Tsukasa Kuroiwa, Akira Katakura, Nobuo Takano, Takahiko Shibahara
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引用次数: 3

摘要

目的探讨舌鳞癌(TSCC)淋巴结阳性(pN+)和淋巴结阴性(pN−)患者的差异表达基因。患者和方法我们检测了20例原发性TSCCs、配对的正常口腔组织、6种TSCCs衍生细胞系和正常口腔角质形成细胞(NOKs)的遗传畸变和基因表达谱。使用Affymetrix 10K SNP图谱阵列对3例pN+病例和2例pN−病例的TSCCs进行全基因组分析,并将结果与正常组织进行比较。我们还检测了确定的候选基因产物的mRNA表达水平。结果发现染色体6q区DNA拷贝数异常与TSCC转移有关。ZDHHC14位于6q25.3,与pN -病例相比,pN+病例的TSCCs增加了一个区域。定量实时逆转录聚合酶链反应显示,与原代培养的NOKs相比,ZDHHC14在所有tscc衍生细胞系中mRNA水平过表达。与tscc来源的细胞系相似,ZDHHC14在原发肿瘤的mRNA水平中明显高频率上调(n = 8/ 20,40 %)。这种上调也与淋巴结状态密切相关(P = 0.0008)。结论ZDHHC14的表达可能与淋巴结转移有关,为TSCC转移的早期发现、预防和治疗提供了新的治疗方案。
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Aberrant expression of the ZDHHC14 gene in squamous cell carcinoma of the human tongue

Objective

The aim of this study was to identify differentially expressed gene(s) among lymph node-positive (pN+) cases and lymph node-negative (pN−) cases of tongue squamous cell carcinoma (TSCC).

Patients and methods

We examined genetic aberrations and gene expression profiles in 20 cases of primary TSCCs, paired normal oral tissues, six TSCC-derived cell lines, and normal oral keratinocytes (NOKs). Whole genome profiling using the Affymetrix 10K SNP Mapping Array was performed on three pN+ cases and two pN− cases of TSCCs and the results were compared to normal tissues. We also examined the mRNA expression level of the candidate gene product identified.

Results

We found that the DNA copy number abnormality of the chromosome 6q region is associated with TSCC metastasis. ZDHHC14 is on 6q25.3, a region gained in pN+ cases of TSCCs compared with pN− cases. Quantitative real-time reverse-transcription polymerase chain reaction showed that ZDHHC14 was overexpressed in all TSCC-derived cell lines compared with primary cultured NOKs at the mRNA level. Similar to the TSCC-derived cell lines, high frequencies of ZDHHC14 up-regulation were evident in mRNA levels of primary tumors (n = 8/20, 40%). This up-regulation also is closely associated with lymph node status (P = 0.0008).

Conclusions

These results suggested that ZDHHC14 expression may be correlated with lymph node metastasis and offers clues to the planning of new treatments such as early detection, prevention, and therapy for TSCC metastasis.

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