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中华普通外科学文献(电子版)

中华普通外科学文献(电子版) ›› 2021, Vol. 15 ›› Issue (02) : 111 -115. doi: 10.3877/cma.j.issn.1674-0793.2021.02.007

所属专题： 文献；

论著

P53蛋白表达与直肠癌术前同步放化疗敏感性研究
王燕1,†(), 张洛1, 潘在用1   
  1. 1. 570203　海口，海南医学院第二附属医院东湖外科
  • 收稿日期:2020-08-12 出版日期:2021-04-01
  • 通信作者: 王燕

Relationship of P53 protein expression with preoperative concurrent chemoradiotherapy sensitivity for rectal cancer

Yan Wang1,†(), Luo Zhang1, Zaiyong Pan1   

  1. 1. Department of Surgery, Donghu Branch of the Second Affiliated Hospital of Hainan Medical College, Haikou 570203, China
  • Received:2020-08-12 Published:2021-04-01
  • Corresponding author: Yan Wang
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引用本文：

王燕, 张洛, 潘在用. P53蛋白表达与直肠癌术前同步放化疗敏感性研究[J]. 中华普通外科学文献(电子版), 2021, 15(02): 111-115.

Yan Wang, Luo Zhang, Zaiyong Pan. Relationship of P53 protein expression with preoperative concurrent chemoradiotherapy sensitivity for rectal cancer[J]. Chinese Archives of General Surgery(Electronic Edition), 2021, 15(02): 111-115.

目的

探讨直肠癌患者组织中P53的表达及其与术前同步放化疗病理反应敏感性的关系。

方法

选取2012年5月至2013年11月于海南医学院第二附属医院就诊的直肠腺癌患者82例，患者放化疗结束后4~6周行直肠切除术，依据RCRG评价同步放化疗敏感性，检测记录放化疗前后P53蛋白阳性细胞所占比例，单因素分析和Logistic多因素回归分析术前同步放化疗病理缓解的影响因素，并对患者进行随访，对患者的生存时间与放化疗后病理RCRG分级进行生存分析。

结果

放化疗后完全缓解（G1）38例（46.34%），放化疗敏感（G1+G2）65例（79.29%）。放化疗后P53蛋白含量明显下降（Z=-3.611，P<0.05）；放化疗前P53高表达（OR=1.853，95% CI：1.144~3.002，P=0.012）、临床降期（OR=1.982，95% CI：1.268~3.098，P=0.003）为直肠癌术前放化疗敏感性的独立危险因素。所有患者中位生存时间为（46.3±1.4）个月，其中G1+G2患者中位生存时间为（71.3±2.4）个月，放化疗不敏感（G3）患者中位生存时间为（38.2±2.1）个月，两组总生存时间比较，差异有统计学意义（P=0.036）。

结论

直肠癌放化疗后肿瘤组织中P53蛋白表达显著下降，且P53高表达的直肠癌患者术前放化疗后敏感性更高。P53的表达水平对局部晚期直肠癌患者术前新辅助放化疗临床决策有一定指导意义。

关键词: 直肠肿瘤, P53, 术前同步放化疗
Objective

To investigate the expression of P53 in rectal cancer tissues and its relationship with the sensitivity of preoperative concurrent chemoradiotherapy.

Methods

Eighty-two cases of rectal adenocarcinoma were selected from May 2012 to November 2013 in the Second Affiliated Hospital of Hainan Medical College. Patients underwent rectal resection 4-6 weeks after the end of preoperative chemoradiotherapy. The sensitivity of concurrent chemoradiotherapy was evaluated according to RCRG. The proportion of P53 protein positive cells before and after chemoradiotherapy was detected. The influencing factors of pathological remission of preoperative concurrent chemoradiotherapy were analyzed by Logistic regression. The patients were followed up to evaluate the survival of different pathological RCRG classification.

Results

Thirty-eight cases (46.34%) had complete remission (G1) and sixty-five cases (79.29%) were sensitive to chemoradiotherapy (G1+G2). The content of P53 protein decreased significantly after radiotherapy and chemotherapy (Z=-3.611, P<0.05). High expression of P53 (OR=1.853, 95% CI: 1.144-3.002, P=0.012), clinical decline (OR=1.982, 95% CI: 1.268-3.098, P=0.003) were independent risk factors for preoperative chemoradiotherapy sensitivity of rectal cancer. The median survival time of all patients was (46.3±1.4) months, of which the median survival time of (G1+G2) patients was (71.3±2.4) months, and the median survival time of G3 patients was (38.2±2.1) months. The difference between survival time and pathological effective course after radiotherapy and chemotherapy was statistically significant (P=0.036).

Conclusions

P53 protein expression in rectal cancer tumor tissues is significantly decreased after chemoradiotherapy. Patients with high expression of P53 are more sensitive to the treatment, which displays good prognosis value to assess the clinical response of neoadjuvant radiotherapy and chemotherapy in patients with locally advanced rectal cancer.

Key words: Rectal neoplasms, P53, Preoperative concurrent radiotherapy and chemotherapy
图1 放化疗后RCRG示例　A为RCRG1，肿瘤组织完全消失无残留；B为RCRG2，肿瘤组织大部分消失，间质纤维化，仅留单个或小簇肿瘤细胞残余；C为肿瘤病灶大部分残留，组织极少纤维化
表1 放化疗前后直肠癌组织中P53阳性细胞比例变化（例）
放化疗前 放化疗后 合计
（-） （+） （++） （+++）
（-） 6 2 1 1 10
（+） 7 2 1 1 11
（++） 8 3 2 1 14
（+++） 27 12 5 3 47
合计 48 19 9 6 82
表2 影响直肠癌术前同步放化疗病理缓解的单因素分析
项目 例数 G1+G2（例） G3（例） OR 95% CI P值
性别       1.561 0.532~5.844 0.137
  　男 55 44 11      
  　女 27 21 6      
年龄(岁)       1.032 0.635~4.368 0.097
  　≤60 47 25 22      
  　>60 35 20 15      
肿瘤大小(cm)       3.641 1.723~6.856 0.031
  　≤5 67 35 32      
  　>5 15 8 7      
浸润深度       2.565 0.842~7.549 0.862
  　T3 58 34 24      
  　T4 24 15 9      
放化疗后临床降期       3.758 2.526~4.263 0.021
  　是 47 41 6      
  　否 35 24 11      
放化疗前P53蛋白       6.471 1.426~11.645 0.042
  　高表达 61 52 9      
  　低表达 21 13 8      
表3 预测直肠癌术前同步放化疗敏感性的Logistic多因素回归分析
变量 β SE Wald OR 95% CI P值
放化疗后临床降期 0.684 0.228 9.000 1.982 1.268~3.098 0.003
年龄≤60岁 0.578 0.387 2.231 1.782 0.835~3.806 0.135
肿瘤≤5 cm 0.241 0.181 1.773 1.273 0.892~1.814 0.183
放化疗前P53（++~+++） 0.617 0.246 6.291 1.853 1.144~3.002 0.012
图2 直肠癌放化疗后不同病理RCRG分级患者的生存分析
[1]
Leeds IL, Fang SH. Neoadjuvant therapy for rectal cancer[J]. Dis Colon Rectum, 2018, 61(8): 883-886.
[2]
Sada YH, Tran Cao HS, Chang GJ, et al. Prognostic value of neoadjuvant treatment response in locally advanced rectal cancer[J]. J Surg Res, 2018, 226: 15-23.
[3]
Molnar C, Vlad-Olimpiu B, Marian B, et al. Survival and functional and oncological outcomes following intersphincteric resection for low rectal cancer: short-term results[J]. J Int Med Res, 2018, 46(4): 1617-1625.
[4]
国家卫生计生委医政医管局，中华医学会肿瘤学分会. 中国结直肠癌诊疗规范(2017年版)[J/CD]. 中华普通外科学文献(电子版), 2018, 12(3): 145-159.
[5]
Hendrick LE, Levesque RL, Shibata D, et al. Utility of restaging patients with stage/ rectal cancer following neoadjuvant chemo/XRT: A systematic review[J]. World J Surg, 2020, 44(3): 973-979.
[6]
Persiani R, Biondi A, Francesco P, et al. Transanal total mesorectal excision vs laparoscopic total mesorectal excision in the treatment of low and middle rectal cancer: A propensity score matching analysis[J]. Dis Colon Rectum, 2018, 61(7): 809-816.
[7]
Brady JT, Xu Z, Scarberry KB, et al. Evaluating the current status of rectal cancer care in the US: where we stand at the start of the commission on Cancer’s National Accreditation Program for Rectal Cancer[J]. J Am Coll Surg, 2018, 226(5): 881-890.
[8]
何田丽，马建华，郭加友，等. MDM2、MDMX以及p53在肿瘤中的研究进展[J]. 医学综述, 2017, 23(7): 1338-1341, 1345.
[9]
王政江，王德霞，王政改，等. 结直肠癌中PLCE1、p53基因表达状况及其意义[J]. 临床和实验医学杂志, 2018, 17(3): 247-251.
[10]
Li CC, Liang JA, Chung CY, et al. Effectiveness of intensity-modulated radiotherapy for rectal cancer patients treated with neoadjuvant concurrent chemoradiotherapy: A population-based propensity score-matched analysis[J]. Anticancer Res, 2019, 39(3): 1479-1484.
[11]
Tabchouri N, Eid Y, Manceau G, et al. Neoadjuvant treatment in upper rectal cancer does not improve oncologic outcomes but increases postoperative morbidity[J]. Anticancer Res, 2020, 40(6): 3579-3587.
[12]
Kamran SC, Lennerz JK, Margolis CA, et al. Integrative molecular characterization of resistance to neoadjuvant chemoradiation in rectal cancer[J]. Clin Cancer Res, 2019, 25(18): 5561-5571.
[13]
Ashish P Wasnik, Mahmoud M Al-Hawary. Invited commentary on "MRI evaluation of the response of rectal cancer to neoadjuvant chemoradiation therapy"[J]. Radiographics, 2019, 39(2): 556-568.
[14]
Chen W, Wang W. Nomogram incorporated the number of adjuvant chemotherapy cycles for predicting the prognosis in stage Ⅱ-Ⅲ rectal cancer patients without neoadjuvant therapy[J]. J Clin Oncol, 2019, 37(15_suppl): e15163.
[15]
Huang W, Dang J, Jiang Q, et al. Effect of pelvic bone marrow-sparing on acute hematologic toxicity in rectal cancer patients undergoing chemoradiotherapy[J]. Intern J Radiation Oncol Bio Physics, 2019, 105(1): E165-E166.
[16]
Müller I, Strozyk E, Schindler S, et al. Cancer cells employ nuclear caspase-8 to overcome the p53-dependent G2/M checkpoint through cleavage of USP28[J]. Mol Cell, 2020, 77(5): 970-984, e7.
[17]
Blazic IM, Lilic GB, Gajic MM. Quantitative assessment of rectal cancer response to neoadjuvant combined chemotherapy and radiation therapy: comparison of three methods of positioning region of interest for ADC measurements at diffusion-weighted MR imaging[J]. Radiology, 2017, 282(2): 615.
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