谷胱甘肽 S 转移酶 P1（Ile105Val）变体对 GSTp、磷酸化 c-Jun 激酶和 P53 表型表达风险的影响及其对接受化疗的非小细胞肺癌患者总生存结局的影响。
Impact of glutathione S transferases P1 (Ile105Val) variants on the risk of GSTp, phosphorylated c-Jun kinase, and P53 phenotypic expression and their implications on overall survival outcomes in non-small cell lung cancer patients treated with chemotherapy.
机构信息
Department of Pathology, Dr. Ram ManoharLohia Institute of Medical Sciences, Lucknow 226010, India; Department of Biochemistry, Babu Banarasi Das University, Lucknow 226018, India.
Department of Pathology, Dr. Ram ManoharLohia Institute of Medical Sciences, Lucknow 226010, India.
出版信息
Mutat Res. 2022 Jan-Jun;824:111775. doi: 10.1016/j.mrfmmm.2022.111775. Epub 2022 Jan 31.
AIM
This study focused on GST-M1, T1 null, and P1 Ile105Val variant genotypes associated with the risk of altered expression of GSTp, pJNK, and P53 in NSCLC patients. These markers and overall survival (OS) were correlated with a key set of clinicopathological characteristics.
METHODS
Genotyping of GST- M1, T1 (+/-), and P1 (Ile105Val) was performed using PCR-RFLP.The expression of GSTp, pJNK, and P53 phenotypes was assessed by immunohistochemistry. The Spearman test was used to examine the correlation between GSTp, pJNK, and P53. Kaplan-Meier test was used for OS analysis.
RESULTS
GSTP1 Val/Val and Ile/Val genotypes notably increased GSTp expression by 1.8 and 1.7 fold, respectively (p = 0.04,p = 0.06). GSTP1 Val/Val and Ile/Val genotypes considerably reduced P53 expression by 0.61 and 0.57 fold, respectively (p = 0.03& p = 0.05), respectively. GSTp, pJNK, and P53 were significantly co-expressed (p < 0.001). GSTp and pJNK expression showed a moderate negative correlation (ρ = -0.32, p = 0.046). In contrast, GSTp and P53 expression exhibited a strong negative correlation (ρ = -0.53, p < 0.0001). There was no correlation between P53 and pJNK expression(ρ = 0.07, p = 0.54). The patient's median OS was 8.9 months, and it was significantly related to pack-years, stage, metastasis, and GSTM1(-/-) genotypes (p > 0.05). SQCLC showed poor OS than ADC (5.7 months vs.9.1 months, p = 0.2). Stage IV and metastasis significantly reduced the OS (p = 0.001). The tumour size and lymph nodes reflected poor OS (p = 0.07&p = 0.06). Gemcitabine+Cisplatin and Gefitinib showed a slightly higher rate of survival (9.3 months and 8.1 months) than Pemtrexe+Cisplatin treatment (7.0 months,p = 0.8). Multivariate analysis revealed that pack-years and GSTp were independent predictors for OS (p = 0.03).
CONCLUSION
GSTp, pJNK, and P53 showed interconnected cascading. Age, pack-year, stage, and GSTp were found to be significant predictive factors for OS.Pack-years, GSTp independent OS predictor.
目的
本研究重点关注 GST-M1、T1 缺失和 P1 Ile105Val 变体基因型与非小细胞肺癌（NSCLC）患者 GSTp、pJNK 和 P53 表达改变的风险相关。这些标志物和总生存期（OS）与一组关键的临床病理特征相关。
方法
采用 PCR-RFLP 法检测 GST-M1、T1（+/−）和 P1（Ile105Val）的基因型。采用免疫组织化学法检测 GSTp、pJNK 和 P53 表型的表达。采用 Spearman 检验分析 GSTp、pJNK 和 P53 之间的相关性。采用 Kaplan-Meier 检验进行 OS 分析。
结果
GSTP1 Val/Val 和 Ile/Val 基因型分别显著增加 GSTp 表达 1.8 倍和 1.7 倍（p=0.04，p=0.06）。GSTP1 Val/Val 和 Ile/Val 基因型分别显著降低 P53 表达 0.61 倍和 0.57 倍（p=0.03 和 p=0.05）。GSTp、pJNK 和 P53 显著共表达（p<0.001）。GSTp 和 pJNK 表达呈中度负相关（ρ=-0.32，p=0.046）。相反，GSTp 和 P53 表达呈强负相关（ρ=-0.53，p<0.0001）。P53 和 pJNK 表达之间无相关性（ρ=0.07，p=0.54）。患者的中位 OS 为 8.9 个月，与吸烟包年数、分期、转移和 GSTM1（−/−）基因型显著相关（p>0.05）。SQCLC 的 OS 明显差于 ADC（5.7 个月 vs.9.1 个月，p=0.2）。IV 期和转移显著降低 OS（p=0.001）。肿瘤大小和淋巴结反映了较差的 OS（p=0.07 和 p=0.06）。吉西他滨+顺铂和吉非替尼治疗的生存率（9.3 个月和 8.1 个月）略高于培美曲塞+顺铂治疗（7.0 个月，p=0.8）。多因素分析显示，吸烟包年数和 GSTp 是 OS 的独立预测因素（p=0.03）。
结论
GSTp、pJNK 和 P53 呈相互关联的级联反应。年龄、吸烟包年数、分期和 GSTp 是 OS 的显著预测因素。吸烟包年数、GSTp 是 OS 的独立预测因素。
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