Luo Yujiao, Li Bin, Li Ji, Zhang Yang, Deng Mingyang, Hu Chunhong, Yan Wenzhe, Zhou Zhiguang, Zhang Guangsen
Department of Hematology, Section of Hemostasis and Thrombosis, Institute of Molecular Hematology, The Second XiangYa Hospital, Central South University, Changsha, China.
National Clinical Research Center for Geriatric Disorders, Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, China.
Front Oncol. 2021 Dec 15;11:719085. doi: 10.3389/fonc.2021.719085. eCollection 2021.
The expression of coagulant factor XIII subunit A (FXIII-A) is significantly increased in some types of cancer cells and tumor-associated macrophages (TAMs). However, few studies on plasma FXIII-A in cancer patients have been conducted and have shown contradictory results, so the relationship of plasma FXIII-A with the progression and prognosis of malignant tumors is still unknown. This study explored the association of plasma FXIII-A with a curative effect and the prognosis of patients with malignant solid tumors.
We monitored plasma FXIII-A before and during systemic therapy and assessed its relationship with the curative effect and prognosis of malignant solid tumors, especially non-small cell lung carcinoma (NSCLC), by propensity-adjusted, multivariable logistic regression analysis and survival curve, in a prospective study of 1147 patients with different types of malignant solid tumors. The influencing factors of plasma FXIII-A were also analyzed.
We found that D-dimer (D2) = 1 mg/L was the inflection point for the association between FXIII-A and D2: FXIII-A was significantly negatively correlated with D2 (r = -0.39, 0.01) and FDP (r = -0.40, < 0.01) in D2 > 1 mg/L but uncorrelated with D2 or FDP in D2 ≤ 1 mg/L, which provided a method to find a more realistic plasma FXIII-A level. Plasma FXIII-A was positively correlated with age, platelets, lymphocytes, monocytes and carcinoembryonic antigen (CEA). It was found for the first time that plasma FXIII-A was abnormally significantly increased (FXIII-A > 150%) in post-therapy patients, especially in NSCLC and lung metastasis patients, and the incidence of FXIII-A > 150% in lung adenocarcinoma was 16 times higher than that in lung squamous carcinoma. FXIII-A > 150% proved to be an independent risk factor for disease progression in NSCLC patients (OR=5.74, 95% CI: 1.20-27.60, p = 0.029), predicting poor efficacy. The marked decrease in plasma FXIII-A (FXIII-A < 40%) was related to coagulation disorders and poor prognosis with a short survival time (median survival time of 4 months).
Plasma FXIII-A has the potential to be a real-time biomarker with bidirectional indicator effects to assess curative effects and prognosis in malignant solid tumors, especially NSCLC.
凝血因子 XIII A 亚基（FXIII-A）在某些类型的癌细胞和肿瘤相关巨噬细胞（TAM）中表达显著增加。然而，关于癌症患者血浆 FXIII-A 的研究较少，且结果相互矛盾，因此血浆 FXIII-A 与恶性肿瘤进展及预后的关系仍不明确。本研究探讨了血浆 FXIII-A 与恶性实体瘤患者疗效及预后的相关性。
在一项对 1147 例不同类型恶性实体瘤患者的前瞻性研究中，我们监测了全身治疗前后的血浆 FXIII-A，并通过倾向调整多变量逻辑回归分析和生存曲线评估其与恶性实体瘤，尤其是非小细胞肺癌（NSCLC）疗效及预后的关系。还分析了血浆 FXIII-A 的影响因素。
我们发现 D-二聚体（D2）=1mg/L 是 FXIII-A 与 D2 关联的拐点：在 D2>1mg/L 时，FXIII-A 与 D2（r=-0.39，P<0.01）和纤维蛋白降解产物（FDP）（r=- .40，P<0.01）显著负相关，但在 D2≤1mg/L 时与 D2 或 FDP 无相关性，这提供了一种找到更实际血浆 FXIII-A 水平的方法。血浆 FXIII-A 与年龄、血小板、淋巴细胞、单核细胞和癌胚抗原（CEA）呈正相关。首次发现治疗后患者血浆 FXIII-A 异常显著升高（FXIII-A>150%），尤其是 NSCLC 和肺转移患者，肺腺癌中 FXIII-A>150%的发生率比肺鳞癌高 16 倍。FXIII-A>150%被证明是 NSCLC 患者疾病进展的独立危险因素（OR=5.74，95%CI：1.20 - 27.60，P = 0.029），预示疗效不佳。血浆 FXIII-A 显著降低（FXIII-A<40%）与凝血障碍和预后不良相关，生存时间短（中位生存时间为 4 个月）。
血浆 FXIII-A 有潜力成为一种具有双向指示作用的实时生物标志物，用于评估恶性实体瘤，尤其是 NSCLC 的疗效和预后。
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