Go-Ichi-Ni-San 2: A potential biomarker and therapeutic target in human cancers

Cancer incidence and mortality are increasing globally, leading to its rising status as a leading cause of death. The Go-Ichi-Ni-San (GINS) complex plays a crucial role in DNA replication and the cell cycle. The GINS complex consists of four subunits encoded by the GINS1, GINS2, GINS3, and GINS4 genes. Recent findings have shown that GINS2 expression is upregulated in many diseases, particularly tumors. For example, increased GINS2 expression has been found in cervical cancer, gastric adenocarcinoma, glioma, non-small cell lung cancer, and pancreatic cancer. It correlates with the clinicopathological characteristics of the tumors. In addition, high GINS2 expression plays a pro-carcinogenic role in tumor development by promoting tumor cell proliferation and migration, inhibiting tumor cell apoptosis, and blocking the cell cycle. This review describes the upregulation of GINS2 expression in most human tumors and the pathway of GINS2 in tumor development. GINS2 may serve as a new marker for tumor diagnosis and a new biological target for therapy.     

Biomarkers of ageing and frailty may predict COVID-19 severity

Coronavirus Disease 2019 (COVID-19) is caused by the novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) - the culprit of an ongoing pandemic responsible for the loss of over 3 million lives worldwide within a year and a half. While the majority of SARS-CoV-2 infected people develop no or mild symptoms, some become severely ill and may die from COVID-19-related complications. In this review, we compile and comment on a number of biomarkers that have been identified and are expected to enhance the detection, protection and treatment of individuals at high risk of developing severe illnesses, as well as enable the monitoring of COVID-19 prognosis and responsiveness to therapeutic interventions. Consistent with the emerging notion that the majority of COVID-19 deaths occur in older and frail individuals, we researched the scientific literature and report the identification of a subset of COVID-19 biomarkers indicative of increased vulnerability to developing severe COVID-19 in older and frail patients. Mechanistically, increased frailty results from reduced disease tolerance, a phenomenon aggravated by ageing and comorbidities. While biomarkers of ageing and frailty may predict COVID-19 severity, biomarkers of disease tolerance may predict resistance to COVID-19 with socio-economic factors such as access to adequate health care remaining as major non-biomolecular influencers of COVID-19 outcomes.     

The prognostic value of elevated neutrophil–lymphocyte ratio for cardiac surgery-associated acute kidney injury: A systematic review and meta-analysis

Background

Patients undergoing cardiac surgery are at significant risk of developing postoperative acute kidney injury (AKI). Neutrophil–lymphocyte ratio (NLR) is a widely available inflammatory biomarker which may be of prognostic value in this setting.

Methods

We conducted a systematic review and meta-analysis of studies reporting associations between perioperative NLR with postoperative AKI. We searched Medline, Embase and the Cochrane Library, without language restriction, from inception to May 2022 for relevant studies. We meta-analysed the reported odds ratios (ORs) with 95% confidence intervals (CIs) for both elevated preoperative and postoperative NLR with risk of postoperative AKI and need for renal replacement therapy (RRT). We conducted a meta-regression to explore inter-study statistical heterogeneity.

Results

Twelve studies involving 10,724 participants undergoing cardiac surgery were included, with eight studies being deemed at high risk of bias using PROBAST modelling. We found statistically significant associations between elevated preoperative NLR and postoperative AKI (OR 1.45, 95% CI 1.18–1.77), as well as postoperative need for RRT (OR 2.37, 95% CI 1.50–3.72). Postoperative NLR measurements were not of prognostic significance.

Conclusions

Elevated preoperative NLR is a reliable inflammatory biomarker for predicting AKI following cardiac surgery.     

Survivin as a diagnostic and therapeutic marker for thyroid cancer

Thyroid cancer (TC) is known as the most prevalent form of endocrine malignancy. With regard to high heterogeneity of the nodules, problem of discriminating between benign and malignant ones in terms of pathological characteristics, as well as lack of appropriate molecular markers; significant efforts are being made to identify molecular markers that able to detect tumorous lesions. Survivin, the newest member of the family of proteins inhibiting cell apoptosis, has been recently considered as a novel molecule marker for cancer. Studies on TC have also demonstrated distinctive expression of survivin and its splice variants in cancer cells compared to normal ones. Therefore, detection of survivin expression and its new splice variants can be utilized to identify tumor nodules and distinguish them from non-cancerous ones, along with other routine laboratory methods.     

Differential Expression of PD-L1 Between Sporadic and VHL-Associated Hereditary Clear-Cell Renal Cell Carcinoma and Its Correlation With Clinicopathological Features

Background

Programmed death ligand-1 (PD-L1) is a potential predictive biomarker for immunotherapy in several malignancies. However, the expression level and clinical significance of PD-L1 in von Hippel–Lindau (VHL)-associated hereditary clear-cell renal cell carcinoma (ccRCC) remain unclear.

EARLY COPD: determinantes de la aparición y progresión de la enfermedad pulmonar obstructiva crónica en adultos jóvenes. Protocolo de un estudio caso-control con seguimiento

Introduction and objectivesDeterminants of chronic obstructive pulmonary disease (COPD) in the early stages of its natural history are not well known. Improving our knowledge of these factors will help to design interventions that can modify prognosis.Study objectives are: a) to characterize a COPD population of young adults aged 35-50 years from a multidimensional point of view; b) to compare these patients with smokers with normal lung function; and c) to create a cohort of young adults aged 35-50 years (smokers or former smokers), with and without COPD, who will be followed in the future to improve understanding of the natural history of the disease.Participants and methodThis is a case-control multicenter study aimed at establishing a well-characterized cohort of young adults, smokers or former-smokers, with and without COPD, for subsequent follow-up.A total of 311 participants (101 cases and 210 controls) were selected from approximately 30 primary care settings and 12 hospitals in 8 Spanish regions. Subjects were smokers or former smokers (> 10 pack-years) aged 35-50 years. Diagnosis of COPD was based on a post-bronchodilator result of FEV1/FVC < 70%.The main study variables were: questionnaires on health, symptoms, exacerbations and daily physical activity, lung function tests, blood and sputum samples, and low-dose computed tomography. In the statistical analysis, COPD patient characteristics will be described and compared with control subjects using a logistic regression analysis.