非典型钙黏素1与食管鳞癌临床病理特征及预后的关系

Association of FAT atypical cadherin 1 with clinicopathological parameters and prognosis in esophageal squamous cell carcinoma

  • 摘要:
    目的 探讨非典型钙黏素1(FAT1)与食管鳞癌临床病理特征及预后的关系。
    方法 采用回顾性队列研究方法。收集2011年1月至2015年12月山西省肿瘤医院收治的124例食管鳞癌病人的临床病理资料;男85例,女39例;中位年龄为60岁,年龄范围为40~72岁。收集手术切除食管鳞癌组织及癌旁组织标本,制备组织芯片,行免疫组织化学染色检测。收集5对新鲜食管鳞癌组织及其相应癌旁组织进行实时荧光定量PCR(qRT‑PCR)。观察指标:(1)食管鳞癌组织和癌旁组织中FAT1蛋白表达情况。(2)食管鳞癌组织和癌旁组织中FAT1 RNA表达情况。(3)食管鳞癌组织中FAT1蛋白表达及与病人临床病理因素的关系。(4)随访和生存情况。采用门诊和电话方式进行随访,了解病人生存情况。随访时间截至2019年2月13日。生存时间定义为手术日至病人肿瘤相关死亡或随访截止时间。正态分布的计量资料以x±s表示,组间比较采用t检验。偏态分布的计量资料以M(范围)表示。计数资料以绝对数或百分比表示,组间比较采用χ²检验。等级资料比较采用非参数秩和检验。采用Kaplan‑Meier法计算生存时间,采用Log‑rank检验进行生存分析。
    结果 (1)食管鳞癌组织和癌旁组织中FAT1蛋白表达情况:124例标本中,因组织脱落,最终获得食管鳞癌组织107例、癌旁组织93例;其中76例标本成功完成食管鳞癌及其癌旁组织配对。免疫组织化学染色检测结果显示:FAT1蛋白在食管鳞癌组织和癌旁组织中均有表达,阳性表达为棕黄色,FAT1定位在细胞膜,以FAT1的表达≥75为高表达,<75为低表达。76例食管鳞癌组织和癌旁组织中FAT1蛋白的相对表达量分别为68±42和77±37,两者比较,差异有统计学意义(t=2.380,P<0.05)。(2)食管鳞癌组织和癌旁组织中FAT1 RNA表达情况。qRT‑PCR检测结果显示:5例食管鳞癌组织和癌旁组织标本中FAT1 RNA的相对表达量分别为1.6±0.4和2.5±0.3,两者比较,差异有统计学意义(t=3.560,P<0.05)。(3)食管鳞癌组织中FAT1蛋白表达及与病人临床病理因素的关系107例食管鳞癌病人中,58例FAT1蛋白高表达。107例食管鳞癌病人中,65例不饮酒,42例饮酒,其FAT1蛋白高表达分别为42例和16例,两者比较,差异有统计学意义(χ²=7.229,P<0.05)。(4)随访和生存情况:107例食管鳞癌病人中,96例获得随访,随访时间为38.0~94.9个月,中位随访时间为45.9个月。生存分析结果显示:FAT1高表达和低表达病人中位生存时间分别为24个月和22个月,两者生存情况比较,差异无统计学意义(χ²=1.773,P>0.05)。亚组分析结果显示:女性、无吸烟史、无饮酒史FAT1高表达和低表达病人中位生存时间分别为24个月和21个月、23个月和22个月、23个月和21个月,生存情况比较,差异均有统计学意义(χ²=8.769,12.827,10.724,P<0.05)。
    结论 FAT1在食管鳞癌中低表达。女性、不吸烟、不饮酒高表达FAT1的食管鳞癌病人预后较好。

     

    Abstract:
    Objective To investigate the association of FAT atypical cadherin 1 (FAT1) with clinicopathological parameters and prognosis in esophageal squamous cell carcinoma (ESCC).
    Methods The retrospective cohort study was conducted. The clinicopathological data of 124 patients with ESCC who were admitted to Shanxi Cancer Hospital from January 2011 to December 2015 were collected. There were 85 males and 39 females, aged from 40 to 72 years, with a median age of 60 years. The ESCC tissues surgically removed and adjacent tissues specimens were collected to prepare tissue microarray for immunohistochemical staining. The 5 cases of ESCC tissues and adjacent tissues were analyzed by real-time quantitative polymerase chain reaction (qRT-PCR). Observation indicators: (1) the expression of FAT1 protein in ESCC and adjacent tissues; (2) the expression of FAT1 RNA in ESCC and adjacent tissues; (3) the expression of FAT1 protein in ESCC tissues and its association with clinicopathological parameters; (4) follow-up and survival. Follow-up using outpatient examination and telephone interview was conducted to detect survival of patients up to February 13, 2019. The survival time was from surgical date to tumor-related death or endpoint of follow-up. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M (range). Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Comparison of ordinal data was analyzed using the non parameter rank sum test. The Kaplan-Meier method was used to calculate survival time, and Log-rank test was used for survival analysis.
    Results (1) The expression of FAT1 protein in ESCC and adjacent tissues: of 124 specimens, the 107 cases of ESCC tissues and 93 cases of adjacent tissues were finally obtained because of exfoliative tissues. There were 76 cases of ESCC tissues and corresponding adjacent tissues matched. Results of immuno-histochemical staining showed that FAT1 protein was expressed in both ESCC and adjacent tissues and was brown after staining. FAT1 was located in cytomembrane, with high expression of FAT1 as ≥75 and low expression as <75. The relative expression levels of FAT1 protein in ESCC and adjacent tissues were 68±42 and 77±37, showing a significant difference between ESCC and adjacent tissues (t=2.380, P<0.05). (2) The expression of FAT1 RNA in ESCC and adjacent tissues: results of qRT-PCR showed that the relative expression levels of FAT1 RNA in 5 cases of ESCC and adjacent tissues were 1.6±0.4 and 2.5±0.3, with a significant difference between them (t=3.560, P<0.05). (3) The expression of FAT1 protein in ESCC tissues and its association with clinicopathological parameters: of the 107 ESCC patients, 58 cases had high expression of FAT1. There were 42 and 16 cases with high expression of FAT1 in 65 non-drinking patients and 42 drinking patients, respectively, showing a significant difference between them (χ²=7.229,P<0.05). (4) Follow-up and survival: 96 of 107 ESCC patients were followed up for 38.0‒94.9 months, with a median follow-up time of 45.9 months. Survival analysis showed that the survival time of patients with high FAT1 expression was 24 months, versus 22 months of patients with low FAT1 expression, indicating no significant difference between them (χ²=1.773, P>0.05). Results of subgroup analysis showed that the survival time was 24 months and 21 months of female patients with high and low FAT1 expression, 23 months and 22 months of non-smoking patients with high FAT1 expression and low FAT1 expression, 23 months and 21 months of non-drinking patients with high FAT1 expression and low FAT1 expression, respectively, showing significant differences between them (χ²=8.769, 12.827, 10.724, P<0.05).
    Conclusions The expression of FAT1 in ESCC tissues is low. Female, non-smoking and non-drinking ESCC patients with high FAT1 expression have good survival.

     

/

返回文章
返回