The biomarkers and potential pathogenesis of lung cancer related cerebral hemorrhage

Abstract

Cerebral hemorrhage is one of the common complications in patients with lung cancer (LC). Although cancer related cerebral hemorrhage was aware, the pathogenesis and biomarkers of lung cancer related cerebral hemorrhage (LCRCH) remained not well known. The aim of this study was to investigate the pathogenesis and plasma biomarkers of LCRCH. A retrospective review was conducted on acute cerebral hemorrhage patients with active LC who was admitted to the hospital between January 2007 and December 2017. A total of 56 patients with LCRCH (active LC patients with acute cerebral hemorrhage but without conventional vascular risks) was recruited. Meanwhile, 112 patients with active LC alone and gender, age, and subtype of cancer cell matched were recruited as control group. In LCRCH patients, most of the hemorrhagic lesions were located in lobes. And most of them with adenocarcinoma were in medium to terminal stage with poor prognosis short-term. Moreover, LCRCH patients had a lengthened prothrombin time (PT), elevated plasma carcinoembryonic antigen (CEA), cancer antigen 125 (CA125) and cancer antigen 199 (CA199) levels and decreased platelet (PLT) level than did the patients with LC. Multivariate logistic regression analysis showed that lengthened PT, elevated plasm CEA, and CA199 levels were independent risk factors for LCRCH. It was suggested that lengthened PT, elevated plasm CEA and CA199 levels associated with the pathogenesis of LCRCH, and that the Index derived from independent risks should be serve as a specific biomarker of LCRCH.

Ring finger protein 180 is associated with biological behavior and prognosis in patients with non‑small cell lung cancer

“…However, commonly used biomarkers, such as carcino-embryonic antigen and Cyfra21-1, offer low sensitivity and specificity and are not appropriate for clinical applications (3,4). Novel molecular or immunohistochemical-based biomarkers may facilitate identification of cancer at an early stage in the future (5). Therefore, there is a need for the development of novel markers.…”

Clinical features of intracerebral hemorrhage in patients with colorectal cancer and its underlying pathogenesis

“…Previous studies revealed that carcinoma mucins were overexpressed by malignant cells and were shown to play a multifaceted role in the initiation, progression, metastasis and subsequent colonization of multiple malignancies[ 27 , 28 ]. In a clinical study of lung cancer-related ICH, elevated plasma CEA and CA199 Levels were independent risk factors for ICH in patients with active lung cancer[ 13 ]. The researchers hypothesized that elevated cancer markers could activate platelets and lead to increased platelets, hypercoagulability, and eventually thrombotic events in the early stage of cancer; however, in the later stage, elevated cancer markers could lead to decreased platelets due to consumption, coagulopathy, and finally hemorrhagic events.…”

“…The National Institute of Health Stroke Scale (NIHSS) was used to evaluate the severity of focal neurological deficits. To minimize the effects of CRC progression on physical activities, patients’ functional prognosis on the 30th day after hemorrhage was measured using the modified Rankin Scale (mRS), and a mRS score > 3 was regarded as a poor prognosis[ 13 ]. According to a research study by Navi and colleagues on ICH[ 2 ], coagulopathy was identified if any of the following parameters were fulfilled: platelets < 100 × 10 9 /L, international normalized ratio (INR) > 1.5, activated partial thromboplastin time (APTT) > 45 s, prothrombin time (PT) > 15 s, and disseminated intravascular coagulation (DIC) (fibrinogen < 200 mg/dL and D-dimer > 290 ng/dL).…”

Clinical Characteristics and Risk Factors of Cerebral Hemorrhage in Patients with Occult Malignant Tumors

“…Tumor markers were detected in eight of the 23 patients, all of whom had one or more elevated tumor marker levels, which indicated that lung CT and tumor markers were necessary to improve the detection rate of combined lung cancer when the cause of intracerebral hemorrhage is unknown; previous studies have also shown that elevated plasma CEA and CA199 levels are associated with the pathogenesis of lung cancer related cerebral hemorrhage (LCRCH), and that the index derived from independent risks should serve as a specific biomarker of LCRCH. 26 …”

“…In addition, according to the definition of coagulation dysfunction, 16 in this study, 12 of the 23 patients had coagulation dysfunction manifesting mainly as prolonged PT and elevated D-dimer levels, which is consistent with the findings of previous reports and suggests that thrombin dysfunction is a possible mechanism of tumor-related intracerebral hemorrhage. 14,26 Moreover, this indicates that abnormal coagulation may be the main cause of intracerebral hemorrhage in patients who do not have conventional vascular risk factors; however, coagulation dysfunction only accounts for a small proportion of common cerebral hemorrhage. 27 Some studies have shown that the most common causes of malignant tumor-related ICH may be intratumoral hemorrhage and abnormal coagulation, 10,16 and abnormal coagulation is usually caused by a variety of mechanisms, including abnormal platelet and abnormal coagulation factors.…”