Coagulation Factor XIII Subunit A Is a Biomarker for Curative Effects and Prognosis in Malignant Solid Tumors, Especially Non-small Cell Lung Cancer

BackgroundThe 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.MethodsWe 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.ResultsWe 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, p < 0.01) and FDP (r = -0.40, p < 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).ConclusionsPlasma 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.

Download Full-text

Relationships of Coagulation Factor XIII Activity with Cell-Type and Stage of Non-Small Cell Lung Cancer

Yonsei Medical Journal ◽

10.3349/ymj.2013.54.6.1394 ◽

2013 ◽

Vol 54 (6) ◽

pp. 1394 ◽

Cited By ~ 10

Author(s):

Seung Heon Lee ◽

In Bum Suh ◽

Eun Joo Lee ◽

Gyu Young Hur ◽

Sung Yong Lee ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Factor Xiii ◽

Coagulation Factor ◽

Small Cell ◽

Cell Type ◽

Small Cell Lung ◽

Coagulation Factor Xiii

Download Full-text

A phase I safety and tolerability study of vorinostat (V) in combination with sorafenib (S) in patients with advanced solid tumors, with exploration of two tumor-type specific expanded cohorts at the recommended phase II dose (renal and non-small cell lung carcinoma).

Journal of Clinical Oncology ◽

10.1200/jco.2010.28.15_suppl.2562 ◽

2010 ◽

Vol 28 (15_suppl) ◽

pp. 2562-2562 ◽

Cited By ~ 2

Author(s):

A. Dasari ◽

L. Gore ◽

W. A. Messersmith ◽

S. Diab ◽

A. Jimeno ◽

...

Keyword(s):

Phase I ◽

Solid Tumors ◽

Lung Carcinoma ◽

Small Cell Lung Carcinoma ◽

Small Cell ◽

Tumor Type ◽

Advanced Solid Tumors ◽

Small Cell Lung ◽

Cell Lung Carcinoma ◽

Recommended Phase Ii Dose

Download Full-text

Risk factors affecting survival after brain metastases from non—small cell lung carcinoma: a follow-up study of 70 patients

Journal of Neurosurgery ◽

10.3171/jns.2001.95.4.0595 ◽

2001 ◽

Vol 95 (4) ◽

pp. 595-600 ◽

Cited By ~ 26

Author(s):

John M. Abrahams ◽

Maria Torchia ◽

Mary Putt ◽

Larry R. Kaiser ◽

Kevin D. Judy

Keyword(s):

Brain Metastases ◽

Survival Time ◽

Lung Carcinoma ◽

Median Survival Time ◽

Small Cell Lung Carcinoma ◽

Small Cell ◽

Small Cell Lung ◽

Cell Lung Carcinoma ◽

Content Type ◽

Fine Print

Object. The authors present their experience with the treatment of brain metastases from non—small cell lung carcinoma (NSCLC). Methods. A retrospective review was conducted in which records from 74 patients treated at the authors' institution between 1994 and 1999 were assessed. Survival and functional outcome were reviewed relative to individual patient variables. The median survival time was 12.9 months, with 1-, 2-, and 5-year survival milestones reached by 52.2%, 30.7%, and 18.1% of patients, respectively. Patients were stratified into groups composed of those with synchronous brain metastases (tumors diagnosed within 3 months of NSCLC) and metachronous brain metastases (tumors diagnosed 3 months after NSCLC). The median survival time and 5-year survival rate were 18 months and 28.9% for metachronous, compared with 9.9 months and 0% for synchronous brain metastases. In univariate analyses, the stage of brain metastases, an initial Karnofsky Performance Scale (KPS) score of 90 or less, and conservative therapy for NSCLC were associated with worse outcomes (p < 0.05). In analyses in which tumors were stratified by synchronous compared with metachronous brain metastases, a preoperative KPS score of 90 or less and radiation therapy (RT) alone for brain metastases were associated with worse outcomes in patients with metachronous brain metastases but not with synchronous tumors (p < 0.05). When stratified by preoperative KPS score, the synchronous brain metastases stage or treatment of brain metastases with RT alone were associated with worse outcome in patients with KPS scores of 100, but had no discernible effect on patients with KPS scores of 90 or less (p < 0.05). Conclusions. The tumor stage and preoperative KPS score were significantly associated with survival. Craniotomy plus RT significantly improved the prognosis in patients with metachronous brain metastases or those with a preoperative KPS score of 100.

Download Full-text

Phase II Study of Ifosfamide Combined with Mesna Uroprotection in Advanced Non-Small-Cell Lung Carcinoma and Other Solid Tumors

Tumori Journal ◽

10.1177/030089168407000508 ◽

1984 ◽

Vol 70 (5) ◽

pp. 433-437 ◽

Cited By ~ 4

Author(s):

Maria Teresa Nobile ◽

Riccardo Rosso ◽

Fulvio Brema ◽

Angela Cinquegrana ◽

Leonardo Santi

Keyword(s):

Solid Tumors ◽

Phase Ii ◽

Lung Carcinoma ◽

Phase Ii Study ◽

Small Cell Lung Carcinoma ◽

Small Cell ◽

Small Cell Lung ◽

Cell Lung Carcinoma

Download Full-text

Dynamics of coagulation factor XIII activity after video-assisted thoracoscopic lobectomy for non-small cell lung cancer

Journal of Thoracic Disease ◽

10.21037/jtd.2019.12.08 ◽

2019 ◽

Vol 11 (12) ◽

pp. 5382-5389

Author(s):

Suguru Shirai ◽

Yoshikane Yamauchi ◽

Fumi Yokote ◽

Takashi Sakai ◽

Yuichi Saito ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Factor Xiii ◽

Coagulation Factor ◽

Small Cell ◽

Small Cell Lung ◽

Video Assisted ◽

Thoracoscopic Lobectomy ◽

Coagulation Factor Xiii

Download Full-text

Combination Therapy of Navitoclax with Chemotherapeutic Agents in Solid Tumors and Blood Cancer: A Review of Current Evidence

Pharmaceutics ◽

10.3390/pharmaceutics13091353 ◽

2021 ◽

Vol 13 (9) ◽

pp. 1353

Author(s):

Nur Syahidah Nor Hisam ◽

Azizah Ugusman ◽

Nor Fadilah Rajab ◽

Mohd Faizal Ahmad ◽

Michael Fenech ◽

...

Keyword(s):

Combination Therapy ◽

Solid Tumors ◽

Small Cell Lung Carcinoma ◽

Chemotherapeutic Agents ◽

Small Cell ◽

Current Evidence ◽

Small Cell Lung ◽

Combination Strategy ◽

Cell Lung Carcinoma ◽

Anti Cancer

Combination therapy emerges as a fundamental scheme in cancer. Many targeted therapeutic agents are developed to be used with chemotherapy or radiation therapy to enhance drug efficacy and reduce toxicity effects. ABT-263, known as navitoclax, mimics the BH3-only proteins of the BCL-2 family and has a high affinity towards pro-survival BCL-2 family proteins (i.e., BCL-XL, BCL-2, BCL-W) to induce cell apoptosis effectively. A single navitoclax action potently ameliorates several tumor progressions, including blood and bone marrow cancer, as well as small cell lung carcinoma. Not only that, but navitoclax alone also therapeutically affects fibrotic disease. Nevertheless, outcomes from the clinical trial of a single navitoclax agent in patients with advanced and relapsed small cell lung cancer demonstrated a limited anti-cancer activity. This brings accumulating evidence of navitoclax to be used concomitantly with other chemotherapeutic agents in several solid and non-solid tumors that are therapeutically benefiting from navitoclax treatment in preclinical studies. Initially, we justify the anti-cancer role of navitoclax in combination therapy. Then, we evaluate the current evidence of navitoclax in combination with the chemotherapeutic agents comprehensively to indicate the primary regulator of this combination strategy in order to produce a therapeutic effect.

Download Full-text