Relationship between the Platelet Autophagy-related Factor Expression and Peritoneal Metastasis of Gastric Cancer
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摘要:
目的 探讨血小板自噬相关因子表达与胃癌腹膜转移的关系。 方法 回顾2021年1月至2023年5月在湖南省人民医院接受胃癌手术的360例胃癌患者的资料。根据是否出现腹膜转移,将患者分为非腹膜转移组(n = 322)和腹膜转移组(n = 38)。收集以下信息:患者的个人信息(即年龄、性别、体重指数)、肿瘤特征(即位置、大小、病理类型、组织病理学分化、淋巴浸润)。收集所有受试者的血小板,并通过酶联免疫吸附试验(ELISA)测定自噬相关蛋白7(ATG7)、苄氯素1(BECN1)、微管相关蛋白1轻链3(LC3)和sequestosome 1(p62)水平。 结果 在纳入的360名患者中,38例患者发现腹膜转移。与非腹膜转移组相比,腹膜转移组BMI降低(P < 0.05),肿瘤大小、非溃疡性肿瘤、淋巴结转移数量、浸润深度、淋巴管侵犯例数、血小板计数、血小板LC3-Ⅱ水平、血小板ATG7水平、CEA水平均增加(P < 0.05)。多因素Logistic回归分析显示BMI(OR = 1.094),淋巴管侵犯(OR = 2.658),LC3-Ⅱ(OR = 3.793)和ATG7(OR = 2.010)是胃癌患者腹膜转移的独立危险因素(P < 0.05)。LC3-Ⅱ>2.59 ng/mL预测胃癌患者腹膜转移的能力最高(AUC = 0.932),其次为ATG7(AUC = 0.916)。 结论 血小板LC3-Ⅱ、ATG7水平升高和胃癌患者腹膜转移独立相关,并可用于预测腹膜转移的情况,有助于指导个体化治疗。 Abstract:Objective To investigate the relationship between the expression of platelet autophagy related factors and peritoneal metastasis of gastric cancer. Methods The data of 360 patients with gastric cancer who underwent surgery in Hunan Provincial People’ s Hospital from January 2021 to May 2023 were reviewed. Patients were divided into non-peritoneal metastasis group (n = 322) and peritoneal metastasis group (n = 38) according to whether peritoneal metastasis occurred or not. The following information was collected: patient's personal information (i.e. age, sex, body mass index) and tumor characteristics (i.e. location, size, pathological type, histopathological differentiation, lymphatic infiltration). Platelets were collected from all subjects, and the levels of autophagy-associated protein 7(ATG7), benzalkonium chloride 1(BECN1), microtubule-associated protein 1 light chain 3(LC3) and sequestosome 1(p62) were measured by enzyme-linked immunosorbent assay (ELISA). Results Among the 360 patients included, peritoneal metastasis was detected in 38 cases. Compared with the non-peritoneal metastasis group, the peritoneal metastasis group exhibited decreased BMI(P < 0.05), while the tumor size, non-ulcerative tumor, number of lymph node metastasis, infiltration depth, number of cases of lymphatic invasion, platelet count, platelet LC3-II level, platelet ATG7 level and CEA level were increased (P < 0.05). Multivariate logistic regression analysis showed that BMI (OR = 1.094), lymphatic invasion (OR = 2.658), and LC3-II (OR = 3.793) and ATG7(OR = 2.010) were independent influencing factors for peritoneal metastasis in patients with gastric cancer (P < 0.05). LC3-II > 2.59ng/ml had the highest ability to predict peritoneal metastasis in patients with gastric cancer (AUC = 0.932), followed by ATG7(AUC = 0.916). Conclusions Elevated levels of platelet LC3-Ⅱ and ATG7 are independently related to peritoneal metastasis in patients with gastric cancer, and can be used to predict the occurrence of peritoneal metastasis, which is helpful to guide individualized treatment. -
Key words:
- Gastric cancer /
- Platelets /
- Autophagy /
- Peritoneal metastasis
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表 1 患者的临床和病理特征[($\bar x \pm s $)/M(IQR)/n(%)]
Table 1. Clinical and pathological features of patients [($\bar x \pm s $)/M(IQR)/n(%)]
变量 非腹膜转移组(n=322) 腹膜转移组(n=38) Z/t/χ2 P 年龄(岁) 63.15 ± 11.30 65.39 ± 12.38 1.147 0.252 BMI(kg/m2) 21.83 ± 3.04 20.49 ± 3.05 2.573 0.010* 男性 252(78.3) 28(73.7) 0.412 0.521 肿瘤位置 3.394 0.183 胃窦 237(73.6) 23(60.5) 胃体 17(5.3) 2(5.3) 贲门 68(21.1) 13(34.2) 肿瘤TNM分期 2.171 0.538 Ⅰ 36(11.2) 5(13.2) Ⅱ 19(5.9) 4(10.5) Ⅲ 204(63.4) 20(52.6) Ⅳ 63(19.6) 9(23.7) 肿瘤大小(cm) 3.65 ± 1.83 4.80 ± 1.55 3.489 0.001* 分化程度 5.291 0.152 未分化 51(15.8) 9(23.7) 低分化 175(54.3) 24(63.2) 中分化 70(21.7) 3(7.9) 高分化 26(8.1) 2(5.3) 病理类型 6.581 0.010* 非溃疡性 37(11.5) 10(26.3) 溃疡性 285(88.5) 28(73.7) 淋巴结转移数量 1.00(5.00) 8.00(9.00) 6.459 <0.001* 浸润深度 9.305 0.002* T1/T2 102(31.7) 3(7.9) T3/T4 220(68.3) 35(92.1) 淋巴管侵犯 49.323 <0.001* N0 128(39.8) 0(0.0) N1 67(20.8) 6(15.8) N2 73(22.7) 8(21.1) N3 54(16.8) 24(63.2) 实验室指标 中性粒细胞计数(×109/L) 4.47 ± 1.55 3.58 ± 1.15 0.837 0.403 淋巴细胞计数(×109/L) 1.99 ± 0.19 1.42 ± 0.45 1.024 0.306 血小板计数(×109/L) 217.87 ± 64.24 279.74 ± 52.10 5.717 <0.001* 单核细胞计数(×109/L) 0.36 ± 0.01 0.34 ± 0.03 0.800 0.424 白细胞(×109/L) 6.16 ± 1.51 6.20 ± 1.68 0.147 0.883 LC3-Ⅱ(ng/mL) 1.75 ± 0.84 3.04 ± 0.99 8.819 <0.001* ATG7(ng/mL) 2.44 ± 1.58 3.47 ± 2.27 2.702 0.010* BECN1(ng/mL) 3.84 ± 1.37 4.01 ± 1.61 0.707 0.480 p62(ng/mL) 1.79 ± 0.59 1.62 ± 0.50 1.659 0.098 CEA(ng/mL)a 2.50(2.80) 4.90(28.10) 4.801 <0.001* CA199(ng/mL)a 7.00(16.00) 23.00(686.00) 1.920 0.064 AFP(ng/mL)a 2.90(1.80) 2.90(2.10) 0.402 0.688 *P < 0.05,a为M(IQR)。 表 2 多因素Logistic回归分析胃癌患者腹膜转移的危险因素
Table 2. Multivariate Logistic regression analysis of risk factors of peritoneal metastasis in patients with gastric cancer
指标 B SE Wald P OR 95%CI 下限 上限 LC3-Ⅱ 1.333 0.305 19.132 <0.001* 3.793 2.087 6.893 BMI 0.089 0.089 1.000 0.047* 1.094 1.011 1.303 ATG7 0.698 0.253 7.630 0.006* 2.010 1.225 3.299 淋巴管侵犯 0.977 0.300 10.589 0.001* 2.658 1.475 4.788 常量 −11.282 2.521 20.033 <0.001* 0.000 *P < 0.05。 表 3 ROC预测胃癌患者腹膜转移能力的结果
Table 3. ROC results for predicting peritoneal metastasis in gastric cancer patients
变量 截止值 AUC 灵敏度(%) 特异度(%) P 95%CI 下限 上限 BMI 20.56 0.630 60.5 64.4 0.009* 0.532 0.729 淋巴管侵犯 2 0.827 89.5 60.6 <0.001* 0.772 0.882 LC3-Ⅱ 2.59 0.932 86.8 91.5 <0.001* 0.891 0.973 ATG7 2.66 0.916 89.5 78.5 <0.001* 0.882 0.951 *P < 0.05。 -
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