热疗联合同步放化疗对中晚期宫颈癌的临床疗效及血清热休克蛋白90α表达的影响

肖鑫; 盛晓安; 施险峰; 董娟娟; 许娟; 汪超

doi:10.16766/j.cnki.issn.1674-4152.002535

热疗联合同步放化疗对中晚期宫颈癌的临床疗效及血清热休克蛋白90α表达的影响

doi: 10.16766/j.cnki.issn.1674-4152.002535

安徽医科大学附属巢湖医院肿瘤内科，安徽合肥 238000

基金项目:

安徽省卫生健康委科研项目 AHWJ2021b018

详细信息

通讯作者:
汪超, E-mail: wangchao10107@163.com

中图分类号: R737.33 R730.5
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出版历程
- 收稿日期: 2021-11-12
- 网络出版日期: 2022-09-23

Clinical efficacy of hyperthermia combined with concurrent chemoradiotherapy on advanced cervical cancer and influence of serum heat-shock protein 90α expression

Department of Oncology, Chaohu Hospital of Anhui Medical University, Hefei, Anhui 238000, China

摘要

摘要: 目的探讨热疗联合同步放化疗对中晚期宫颈癌患者的临床疗效，宫颈癌患者治疗前后血清中热休克蛋白90α(HSP90α)表达的变化及预测治疗效果的临床价值。方法选取2017年1月—2019年6月安徽医科大学附属巢湖医院收治的80例中晚期宫颈癌患者作为研究对象，将其中单纯同步放化疗治疗的40例患者纳入对照组，在对照组的基础上联合热疗的40例患者纳入研究组，比较2组近期疗效及毒性反应，并检测宫颈癌患者治疗前后血清HSP90α指标的变化。结果研究组总有效率为87.5%，明显优于对照组的65.0%，2组比较差异有统计学意义(P＜0.05)；研究组2年生存率明显高于对照组, 差异有统计学意义(P＜0.05)；2组不良反应发生情况比较差异无统计学意义(均P＞0.05)；宫颈癌患者治疗前后HSP90α变化比较，差异有统计学意义(P＜0.05)。结论热疗联合同步放化疗明显改善了患者近期疗效，没有明显增加治疗副反应，并且提高患者2年的总生存率，治疗有效的中晚期宫颈癌患者血清HSP90α表达水平出现明显下降，疗效较好，值得推广。
- 热疗 /
- 放疗 /
- 化疗 /
- 宫颈癌 /
- 热休克蛋白90α /
- 疗效
Abstract: Objective To investigate the clinical efficacy of hyperthermia combined with concurrent chemoradiotherapy in patients with advanced cervical and endocervical cancer (CESC), the changes in serum heat-shock protein 90α (HSP90α) expression before and after treatment and the value of predicting the therapeutic effect. Methods A total of 80 patients with advanced CESC who were admitted to Chaohu Hospital Affiliated to Anhui Medical University from January 2017 to June 2019 were selected as the research subjects. Amongst then, 40 patients who were treated with simple concurrent chemoradiotherapy were included in the control group. On the basis of the control group, 40 patients with combined hyperthermia were included in the study group. The short-term efficacy and toxicity between the two groups were compared and the changes in serum HSP90α indices in patients before and after treatment were detected. Results The total effective rate of the study group was 87.5%, which was significantly better than that of the control group (65.0%), and the difference was statistically significant (P < 0.05). The 2-year survival rate of the study group was significantly higher than that of the control group (P < 0.05). By contrast, no significant difference was found in the incidence of adverse reactions between the two groups (all P>0.05). In patients, the difference in the comparison of HSP90α changes before and after treatment was statistically significant (P < 0.05). Conclusion Hyperthermia combined with concurrent chemoradiotherapy could significantly improve the short-term curative effect in patients without significantly increasing the side effects of treatment and improve their 2-year overall survival rate. The expression of serum HSP90α decreased significantly in patients with middle-advanced CESC who have been effectively treated and the curative effect is good, hence worthy of promotion.
- Hyperthermia /
- Radiotherapy /
- Chemotherapy /
- Cervical and endocervical cancer /
- Heat shock protein 90α /
- Efficacy

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图 1 2组中晚期宫颈癌患者2年OS比较

Figure 1. Comparison of 2-year overall survival in patients with advanced cervical and endocervical cancer in two groups

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表 1 2组中晚期宫颈癌患者近期疗效比较

Table 1. Comparison of short-term curative effects in patients with advanced cervical and endocervical cancer in two groups

组别	例数	CR[例(%)]	PR[例(%)]	SD[例(%)]	PD[例(%)]	ORR(%)
对照组	40	25(62.5)	10(25.0)	5(12.5)	0	87.5(35/40)
观察组	40	15(37.5)	11(27.5)	10(25.0)	4(10.0)	65.0(26/40)
注：2组ORR比较，χ²=5.591，P=0.018。

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表 2 2组中晚期宫颈癌患者不良反应发生情况比较[例(%)]

Table 2. Comparison of adverse reactions in patients with advanced cervical and endocervical cancer in two groups

组别	例数	分级	消化道反应			泌尿道反应	骨髓抑制			体重下降	皮肤损伤	直肠出血	血尿
组别	例数	分级	恶心	呕吐	腹泻	泌尿道反应	白细胞	血小板	血红蛋白	体重下降	皮肤损伤	直肠出血	血尿
对照组	40	1级	10(25.0)	5(12.5)	7(17.5)	10(25.0)	4(10.0)	7(17.5)	8(20.0)	11(27.5)	0	1(2.5)	9(22.5)
		2级	6(15.0)	7(17.5)	2(5.0)	1(2.5)	17(42.5)	8(20.0)	10(25.0)	2(5.0)	0	0	2(5.0)
		3级	0	0	0	0	10(25.0)	1(2.5)	0	0	0	0	0
		4级	0	0	0	0	2(5.0)	0	0	0	0	0	0
研究组	40	1级	11(27.5)	7(17.5)	6(15.0)	13(32.5)	5(12.5)	8(20.0)	11(27.5)	9(22.5)	0	2(5.0)	7(5.0)
		2级	4(10.0)	3(7.5)	2(5.0)	2(5.0)	16(40.0)	9(22.5)	14(35.0)	3(7.5)	0	1(2.5)	5(10.0)
		3级	0	0	0	0	12(30.0)	1(2.5)	1(2.5)	0	0	0	0
		4级	0	0	0	0	1(2.5)	0	0	0	0	0	0
统计量			0.367^a	0.700^a	0.257^a	0.912^a	0.877^b	0.416^b	0.977^b	0.058^a		0.263^a	0.061^a
P值			0.714	0.484	0.797	0.340	0.381	0.678	0.328	0.809		0.608	0.805
注：^a为χ²值, ^b为Z值。

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表 3 2组中晚期宫颈癌患者治疗前后血清HSP90α表达情况比较(x±s，ng/mL)

Table 3. Comparison of serum HSP90α expression in patients with advanced cervical and endocervical cancer before and after treatment in two groups (x±s, ng/mL)

组别	例数	治疗前	治疗后	t值	P值
对照组	40	106.25±24.68	74.97±22.09	10.452	＜0.001
研究组	40	104.29±27.70	63.50±15.20	6.014	＜0.001
t值		0.334	2.705
P值		0.739	0.009

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表 4 近期不同疗效的患者治疗前后血清HSP90α表达情况比较(x±s，ng/mL)

Table 4. Serum HSP90α expression before and after treatment in patients with different curative effects recently (x±s, ng/mL)

组别	例数	治疗前	治疗后	t值	P值
CR+PR	61	111.18±22.30	62.51±13.41	13.201	＜0.001
SD	15	91.34±21.93^a	86.50±31.78^a	1.903	0.078
PD	4	100.90±28.70^a	94.75±13.01^a	0.298	0.785
F值		9.036	14.839
P值		＜0.001	＜0.001
注：与CR+PR组比较, ^aP＜0.05。

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参考文献(22)

[1]	BRAY F, FERLAY J, SOERJOMATARAM I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6): 394-424. doi: 10.3322/caac.21492
[2]	RODEN R, STERN P L. Opportunities and challenges for human papillomavirus vaccination in cancer[J]. Nat Rev Cancer, 2018, 18(4): 240-254. doi: 10.1038/nrc.2018.13
[3]	WANG R J, PAN W, JIN L, et al. Human papillomavirus vaccine against cervical cancer: Opportunity and challenge[J]. Cancer Lett, 2020, 471: 88-102. doi: 10.1016/j.canlet.2019.11.039
[4]	SHRESTHA A D, NEUPANE D, VEDSTED P, et al. Cervical cancer prevalence, incidence and mortality in low and middle income countries: A systematic review[J]. Asian Pac J Cancer Prev, 2018, 19(2): 319-324.
[5]	肖群, 方燕飞, 孔于兰. 同步放化疗与单纯放疗对中晚期宫颈癌患者的有效性及安全性比较[J]. 中华全科医学, 2018, 16(11): 1813-1815. doi: 10.16766/j.cnki.issn.1674-4152.000493 XIAO Q, FANG Y F, KONG Y L. Comparison of the efficacy and safety of concurrent chemoradiotherapy and radiotherapy alone in patients with advanced cervical and endocervical cancer[J]. Chinese Journal of General Practice, 2018, 16(11): 1813-1815. doi: 10.16766/j.cnki.issn.1674-4152.000493
[6]	邹金金, 刘定义, 刘鸿, 等. 新辅助放化疗联合热疗对进展期直肠癌的应用效果研究[J]. 中外医学研究, 2019, 17(1): 24-25. https://www.cnki.com.cn/Article/CJFDTOTAL-YJZY201901011.htm ZOU J J, LIU D J, LIU H, et al. Study on the effect of neoadjuvant chemoradiotherapy combined with hyperthermia on advanced rectal cancer[J]. Research on Chinese and Foreign Medicine, 2019, 17(1): 24-25. https://www.cnki.com.cn/Article/CJFDTOTAL-YJZY201901011.htm
[7]	郝永杰, 邓军吉, 崔传水, 等. 热疗联合同步放化疗治疗局部晚期非小细胞肺癌疗效观察[J]. 医学食疗与健康, 2020, 18(12): 41-43. https://www.cnki.com.cn/Article/CJFDTOTAL-YXSL202012028.htm HAO Y J, DENG J J, CUI C S, et al. Curative effect observation of hyperthermia combined with concurrent chemoradiotherapy in the treatment of locally advanced non-small cell lung cancer[J]. Medical Diet and Health, 2020, 18(12): 41-43. https://www.cnki.com.cn/Article/CJFDTOTAL-YXSL202012028.htm
[8]	LANG B J, GUERRERO-GIMÉNEZ M E, PRINCE T L, et al. Heat shock proteins are essential components in transformation and tumor progression: Cancer cell intrinsic pathways and beyond[J]. Int J Mol Sci, 2019, 20(18): 4057.
[9]	EISENHAUER E A, THERASSE P, BOGAERTS J, et al. New response evaluation criteria in solid tumours: Revised recist guideline (version 1.1)[J]. Eur J Cancer, 2009, 45(2): 228-247. doi: 10.1016/j.ejca.2008.10.026
[10]	OEI A L, KOK H P, OEI S B, et al. Molecular and biological rationale of hyperthermia as radio- and chemosensitizer[J]. Adv Drug Deliv Rev, 2020, 163: 84-97. DOI: 10.1016/j.addr.2020.01.003.
[11]	HARIMA Y, OHGURI T, IMADA H, et al. A multicentre randomised clinical trial of chemoradiotherapy plus hyperthermia versus chemoradiotherapy alone in patients with locally advanced cervical cancer[J]. Int J Hyperthermia, 2016, 32(7): 801-808. doi: 10.1080/02656736.2016.1213430
[12]	陈剑萍, 叶柳青, 于爱军, 等. 多种肿瘤标志物在宫颈癌诊断中的临床应用分析[J]. 中国卫生检验杂志, 2017, 27(17): 2533-2535. https://www.cnki.com.cn/Article/CJFDTOTAL-ZWJZ201717030.htm CHEN J P, YE L Q, YU A J, et al. Analysis of clinical application of various tumor markers in the diagnosis of cervical and endocervical cancer[J]. Chinese Journal of Health Laboratory Technology, 2017, 27(17): 2533-2535. https://www.cnki.com.cn/Article/CJFDTOTAL-ZWJZ201717030.htm
[13]	BOUDESCO C, CAUSE S, JEGO G, et al. Hsp70: A cancer target inside and outside the cell[J]. Methods Mol Biol, 2018, 1709: 371-396.
[14]	SOUDRY E, STERN S S, HARDY B, et al. Heat shock proteins Hsp90, Hsp70 and GRP78 expression in medullary thyroid carcinoma[J]. Ann Diagn Pathol, 2017, 26(6): 52-56.
[15]	WU J M, LIU T N, RIOS Z, et al. Heat shock proteins and cancer[J]. Trends pharmacol Sci, 2017, 38(3): 226-256. doi: 10.1016/j.tips.2016.11.009
[16]	LEE Y C, CHANG W W, CHEN Y Y, et al. Hsp90α Mediates BMI1 expression in breast cancer stem/progenitor cells through facilitating nuclear translocation of c-Myc and EZH2[J]. Int J Mol Sci, 2017, 18(9): 1986. doi: 10.3390/ijms18091986
[17]	LEE H W, KIM K M. Clinical significance of heat shock protein 90α expression as a biomarker of prognosis in patients with gastric cancer[J]. Niger J Clin Pract, 2019, 22(12): 1698-1705. doi: 10.4103/njcp.njcp_68_19
[18]	WEI W E, LIU M S, NING S F, et al. Diagnostic value of plasma HSP90α levels for detection of hepatocellular carcinoma[J]. BMC Cancer, 2020, 20(1): 6. doi: 10.1186/s12885-019-6489-0
[19]	陈莉萍, 曹婷, 李素芬, 等. Hsp90α及SCC在宫颈癌早期诊断及预后监测中的价值[J]. 西部医学, 2020, 12(1): 76-80. doi: 10.3969/j.issn.1672-3511.2020.01.018 CHEN L P, CAO T, LI S F, et al. The value of Hsp90α and SCC in the early diagnosis and prognosis monitoring of cervical and endocervical cancer[J]. Medical Journal of West China, 2020, 12(1): 76-80. doi: 10.3969/j.issn.1672-3511.2020.01.018
[20]	FU Y, XU X, HUANG D S, et al. Plasma heat shock protein 90alpha as a biomarker for the diagnosis of liver cancer: An official, large-scale, and multicenter clinical trial[J]. EBio Medicine, 2017, 24(2): 56-63.
[21]	HAN S T, CHENG Z Z, ZHAO X Q, et al. Diagnostic value of heat shock protein 90α and squamous cell carcinoma antigen in detection of cervical cancer[J]. J Int Med Res, 2019, 47(11): 5518-5525. doi: 10.1177/0300060519865634
[22]	马庆荣, 余佩芝, 张帆, 等. 热疗中热休克蛋白90对26S蛋白酶体的调控机制[J]. 南方医科大学学报, 2017, 37(4): 537-541. doi: 10.3969/j.issn.1673-4254.2017.04.20 MA Q R, YU P Z, ZHANG F, et al. The regulation mechanism of heat shock protein 90 on 26S proteasome in hyperthermia[J]. Journal of Southern Medical University, 2017, 37(4): 537-541. doi: 10.3969/j.issn.1673-4254.2017.04.20