SLITRK6 基因的差异表达可作为尿路上皮癌特别是上尿路移行细胞癌的潜在治疗靶点。

Differential expression of SLITRK6 gene as a potential therapeutic target for urothelial carcinoma in particular upper tract cancer.

机构信息

Department of Urology, Sheri-Kashmir Institute of Medical Sciences, (SKIMS), Srinagar 190011, J&K, India.

Department of Advanced Centre for Human Genetics, SKIMS, Srinagar 190011, J&K, India.

出版信息

Gene. 2023 Aug 20;878:147583. doi: 10.1016/j.gene.2023.147583. Epub 2023 Jun 22.

DOI:10.1016/j.gene.2023.147583

PMID:37353040

Abstract

BACKGROUND

Urinary bladder urothelial carcinoma (UBUC) and upper tract urothelial carcinoma (UTUC) harbor analogous morphology with comparable cytogenetic changes as well as prognostic factors but their similar biological activities still remain controversial. SLITRK6 gene has been demonstrated to have distinct role in urothelial cancers with a distinction between UTUC and UBUC.

METHOD

The study included a total of 80 patients of urothelial carcinoma including 60 UBUC and 20 UTUC cases. The tumor tissues from both the groups were evaluated for gene expression at mRNA level by qRT-PCR, and protein expression by immunohistochemistry (IHC) and western blot.

RESULTS

Significantly more than 4-fold high mRNA expression of SLITRK6 was observed in UTUC against 1.2-fold in UBUC (p < 0.0001). The overall SLITRK6 expression by IHC was observed in 80% of the UBUC cases in comparison to 100% strong expression in UTUC patients and among two groups expression exhibited a significant difference for moderate to strong expression (p = 0.0005). The protein expression by western blot analysis in UTUC samples was considerably higher as compared to UBUC samples (1.64 vs. 0.76 respectively: p = 0.01). A strong concordance exhibited for the higher mRNA and protein expression in both UTUC and UBUC cases (∼75%) wherein 80%, 75% and 70% higher expression of SLITRK6 was detected by qRT-PCR, Western blot and IHC respectively.

CONCLUSION

To conclude, although SLITRK6 exhibits a strong expression in both UTUC and UBUC but was considerably observed higher in majority of UTUC cases. Therefore, SLITRK6 appears as a promising novel possible gene target for urothelial carcinoma in particular UTUC.

摘要

背景

膀胱尿路上皮癌（UBUC）和上尿路尿路上皮癌（UTUC）具有相似的形态学特征，具有类似的细胞遗传学改变和预后因素，但它们的相似生物学活性仍存在争议。SLITRK6 基因在尿路上皮癌中具有明显的作用，能够区分 UTUC 和 UBUC。

方法

本研究共纳入 80 例尿路上皮癌患者，其中 UBUC 患者 60 例，UTUC 患者 20 例。采用 qRT-PCR 检测两组患者肿瘤组织的基因表达水平，采用免疫组织化学（IHC）和 Western blot 检测蛋白表达水平。

结果

UTUC 中 SLITRK6 的 mRNA 表达水平明显高于 UBUC，是 UBUC 的 4 倍以上（p<0.0001）。IHC 检测显示，80%的 UBUC 病例存在 SLITRK6 表达，而 100%的 UTUC 患者存在强烈表达，两组间表达差异具有统计学意义（p=0.0005）。UTUC 样本的 Western blot 分析显示，蛋白表达明显高于 UBUC 样本（分别为 1.64 和 0.76：p=0.01）。UTUC 和 UBUC 病例的 mRNA 和蛋白表达均具有较强的一致性（∼75%），其中 qRT-PCR、Western blot 和 IHC 分别检测到 SLITRK6 的表达水平分别高出 80%、75%和 70%。