热休克相关蛋白HSPH1在宫颈癌组织中的表达及其与预后的相关性分析-东南大学学报医学版

热休克相关蛋白HSPH1在宫颈癌组织中的表达及其与预后的相关性分析

单位：西安市人民医院/西安市第四医院, 陕西西安 710000

分类号：R737.33

出版年·卷·期（页码）：2024·43·第四期（540-547）

摘要：

目的: 分析热休克蛋白家族 H(Hsp110)成员 1[heat shock protein family H(Hsp110) member 1,HSPH1]在宫颈癌组织中的表达及其与预后的相关性。方法: 收集2018年2月至2021年1月首次确诊的60例宫颈癌患者的癌组织和相邻非癌组织。通过qRT-PCR检测HSPH1表达,分析其与肿瘤标志物、宫颈癌病理特征之间的关系,并通过Cox回归模型确定3年生存的独立预后因子。利用时间依赖性受试者工作特征(ROC)曲线评估HSPH1预测1年、2年和3年生存的临床价值,并通过外部数据库和细胞实验验证结果。结果: HSPH1在临床样本和GSE29570数据库宫颈癌组织中均呈高表达(P＜0.05),且与CA125、CA19-9、CEA和SCCA呈正相关(均r＞0,P＜0.05)。高表达组(≥1.57)肿瘤大小≥4 cm、FIGO Ⅲ~Ⅳ期、淋巴结转移及淋巴血管空间侵犯比例均高于低表达组(P＜0.05)。TCGA数据库和临床样本分析显示,高表达组患者生存率显著低于低表达组(P＜0.01)。多因素Cox回归分析显示,HSPH1<1.57(HR=0.299,P=0.039)和无淋巴结转移(HR=0.245,P=0.003)是独立预后因子。HSPH1预测1年、2年和3年生存的曲线下面积分别为0.82、0.85和0.88。结论: HSPH1在宫颈癌组织中的高表达与患者较差的预后之间存在显著相关,HSPH1可作为宫颈癌预后评估和治疗靶点的潜在生物标志物。

Objective: To analyze the expression of heat shock protein family H(Hsp110) member 1(HSPH1) in cervical cancer tissues and its correlation analysis with prognosis. Methods: Cancerous tissues and adjacent non-cancerous tissues of 60 cervical cancer patients diagnosed for the first time from February 2018 to January 2021 were collected. HSPH1 expression was detected by qRT-PCR, its association with tumor markers was assessed, the association between HSPH1 and pathological features of cervical cancer was analyzed, and independent prognostic factors for three-year survival were determined by Cox regression model. The clinical value of HSPH1 in predicting 1-, 2-and 3-year survival was assessed using time-dependent ROC curves, and the results were validated by external databases and cellular experiments. Results: HSPH1 was highly expressed in cervical cancer tissues in clinical samples and the GSE29570 database(P<0.05) and positively correlated with CA125, CA19-9, CEA and SCCA(all r＞0,P<0.05). The proportions of tumor ≥4 cm, FIGO stage Ⅲ-Ⅳ, lymph node metastasis and lymphovascular space invasion were higher in the high-expression group(≥1.57) than in the low-expression group(P<0.05). Analysis of the TCGA database and clinical samples showed that the survival rate of patients in the high-expression group was significantly lower than that in the low-expression group(P<0.01). Multifactorial Cox regression analysis showed that HSPH1<1.57(HR=0.299,P=0.039) and without lymph node metastasis(HR=0.245,P=0.003,) were independent prognostic factors. The area under the curve for HSPH1 predicting 1-, 2-, and 3-year survival was 0.82, 0.85, and 0.88, respectively. Conclusion: High expression of HSPH1 in cervical cancer tissues is significantly associated with the patients' poorer prognosis, suggesting that HSPH1 may serve as a potential biomarker for prognostic assessment and therapeutic targeting in cervical cancer.

参考文献：

[1] PERKINS R B,WENTZENSEN N,GUIDO R S,et al.Cervical cancer screening:a review[J].JAMA,2023,330(6):547-558.
[2] RERUCHA C M,CARO R J,WHEELER V L.Cervical cancer screening[J].Am Fam Physician,2018,97(7):441-448.
[3] FONTHAM E T H,WOLF A M D,CHURCH T R,et al.Cervical cancer screening for individuals at average risk:2020 guideline update from the American Cancer Society[J].CA Cancer J Clin,2020,70(5):321-346.
[4] 杨美平,邓颂,陈明倩,等.NOB1在宫颈癌患者中的表达及其与预后的相关性分析[J].中国优生与遗传杂志,2024,32(1):97-101.
[5] 任发亮,任巧丽,田志强,等.HSP110与肿瘤免疫[J].免疫学杂志,2018,34(7):641-644.
[6] LIANG Y,LUO J,YANG N,et al.Activation of the IL-1β/KLF2/HSPH1 pathway promotes STAT3 phosphorylation in alveolar macrophages during LPS-induced acute lung injury[J].Biosci Rep,2020,40(3):BSR20193572.
[7] LIU H,ZHANG S,LIU Y,et al.Knockdown of HSP110 attenuates hypoxia-induced pulmonary hypertension in mice through suppression of YAP/TAZ-TEAD4 pathway[J].Respir Res,2022,23(1):1-16.
[8] FAN G,TU Y,WU N,et al.The expression profiles and prognostic values of HSPs family members in head and neck cancer[J].Cancer Cell Intl,2020,20:1-12.
[9] WANG L,WANG C,HE Y,et al.Identification of a prognostic model based on immune and hypoxia-related gene expressions in cervical cancer[J].J Obstet Gynaecol,2023,43(2):2277242.
[10] 周琦,盛修贵.子宫颈癌诊断与治疗指南(2021年版)[J].中国癌症杂志,2021,31(6):474-489.
[11] 赵丽萍.宫颈癌早期筛查的应用与进展综述[J].名医,2018(12):13-14.
[12] 张睿怡,汤艳梅.关于宫颈癌筛查新技术与防控措施的研究综述[J].世界最新医学信息文摘,2019,19(3):27-29.
[13] 刘童童,李顺平.国内外宫颈癌筛查障碍研究综述[J].中国社会医学杂志,2018,35(1):90-93.
[14] SAINI J,SHARMA P K.Clinical,prognostic and therapeutic significance of heat shock proteins in cancer[J].Curr Drug Targets,2018,19(13):1478-1490.
[15] WANG M,LI Z.Prediction of prognosis and immune landscape in cervical cancer based on heat shock protein-related genes[J].Int J Hyperthermia,2023,40(1):2259140.
[16] GOZZI G J,GONZALEZ D,BOUDESCO C,et al.Selecting the first chemical molecule inhibitor of HSP110 for colorectal cancer therapy[J].Cell Death Differ,2020,27(1):117-129.
[17] CAUSSE S Z,MARCION G,CHANTELOUP G,et al.HSP110 translocates to the nucleus upon genotoxic chemotherapy and promotes DNA repair in colorectal cancer cells[J].Oncogene,2019,38(15):2767-2777.
[18] 陈伟,李同斌,刘海涛.ATF3转录调控HSP110对低氧诱导的肺动脉平滑肌细胞自噬和增殖的影响[J].心脏杂志,2022,34(3):249-255,261.
[19] BOUDESCO C,VERHOEYEN E,MARTIN L,et al.HSP110 sustains chronic NF-κB signaling in activated B-cell diffuse large B-cell lymphoma through MyD88 stabilization[J].Blood,2018,132(5):510-520.
[20] 张月,唐隽.以HSP110为佐剂的宫颈癌纳米颗粒疫苗可有效延长荷瘤小鼠存活率[J].免疫学杂志,2018,34(4):277-285.
[21] BERTHENET K,LAGRANGE A,MARCION G,et al.HSP110 promotes colorectal cancer growth through STAT3 activation[J].Oncogene,2017,36(16):2328-2336.
[22] WU L,SHEN B,LI J,et al.STAT3 exerts pro-tumor and anti-autophagy roles in cervical cancer[J].Diagn Pathol,2022,17(1):1-10.
[23] WALCH-RüCKHEIM B,PAHNE-ZEPPENFELD J,FISCHBACH J,et al.STAT3/IRF1 pathway activation sensitizes cervical cancer cells to chemotherapeutic drugs[J].Cancer Res,2016,76(13):3872-3883.
[24] SHAN D,SHANG Y,HU T.MicroRNA-411 inhibits cervical cancer progression by directly targeting STAT3[J].Oncol Res,2019,27(3):349.

服务与反馈：

【文章下载】【发表评论】【查看评论】【加入收藏】

提示：您还未登录，请登录！点此登录