Biomarkers for lung cancer: clinical uses

PURPOSE OF REVIEW: Biomarkers for lung cancer may be used for risk stratification, early detection, treatment selection, prognostication and monitoring for recurrence. All these areas of clinical management would benefit from sensitive and specific, noninvasive, cost-effective biomarkers. RECENT FINDINGS: Significant progress has been made in understanding the steps involved in lung carcinogenesis and in the development of novel technologies for biomarker discovery. Over the last 3 years research into prospective lung cancer biomarkers has proliferated, especially in the areas of early detection and prognostication. The most active areas of research have been in promoter methylation, proteomics and genomics. Many investigators are adopting panels of serum biomarkers in an attempt to increase sensitivity. The development of targeted lung cancer therapy has engendered interest in markers to identify the optimal candidates for these therapies. SUMMARY: Much progress has been made in the last 3 years in the identification and validation of new biomarkers for the early diagnosis of lung cancer. The biomarkers require additional studies before they can be used clinically. Markers to identify lung cancer patients who may benefit from targeted therapy have been developed more rapidly and may be used now in some clinical situations.     

High-resolution computed tomography in the diagnosis of diffuse lung disease: a clinical perspective

High-resolution computed tomography (HRCT) has a central role in the routine detection and diagnosis of individual diffuse lung diseases. The widespread use of HRCT has been stimulated by numerous published series, which have evaluated the accuracy of HRCT in cohorts of patients. However, these series have not simulated the integration of HRCT into clinical diagnosis, and this has led to difficulties in achieving the optimal diagnostic use of HRCT in routine practice. This article summarizes the problems facing the clinician in applying HRCT series to diagnosis in individual patients. The flaws in published series are discussed and the importance of integrating HRCT data with baseline clinical information and, in selected cases, histopathologic findings is highlighted.     

Biomarkers of gastric cancer: Current topics and future perspective

Gastric cancer(GC) is one of the most prevalent malignant types in the world and an aggressive disease with a poor 5-year survival. This cancer is biologically and genetically heterogeneous with a poorly understood carcinogenesis at the molecular level. Although the incidence is declining, the outcome of patients with GC remains dismal. Thus, the detection at an early stage utilizing useful screening approaches, selection of an appropriate treatment plan, and effective monitoring is pivotal to reduce GC mortalities. Identification of biomarkers in a basis of clinical information and comprehensive genome analysis could improve diagnosis, prognosis, prediction of recurrence and treatment response. This review summarized the current status and approaches in GC biomarker, which could be potentially used for early diagnosis, accurate prediction of therapeutic approaches and discussed the future perspective based on the molecular classification and profiling.     

Biomarkers in bladder cancer: Translational and clinical implications

Bladder cancer is associated with high recurrence and mortality rates. These tumors show vast heterogeneity reflected by diverse morphologic manifestations and various molecular alterations associated with these disease phenotypes. Biomarkers that prospectively evaluate disease aggressiveness, progression risk, probability of recurrence and overall prognosis would improve patient care. Integration of molecular markers with conventional pathologic staging of bladder cancers may refine clinical decision making for the selection of adjuvant and salvage therapy. In the past decade, numerous bladder cancer biomarkers have been identified, including various tumor suppressor genes, oncogenes, growth factors, growth factor receptors, hormone receptors, proliferation and apoptosis markers, cell adhesion molecules, stromal factors, and oncoproteins. Recognition of two distinct pathways for urothelial carcinogenesis represents a major advance in the understanding and management of this disease. Nomograms for combining results from multiple biomarkers have been proposed to increase the accuracy of clinical predictions. The scope of this review is to summarize the major biomarker findings that may have translational and clinical implications.     

Biomarkers and transcriptome profiling of lung cancer

Lung cancer is the leading cause of cancer-related deaths worldwide. High-throughput technologies such as microarrays provide an opportunity to explore biomarkers for cancer prevention, prognosis and treatment guidance. Recent studies have revealed many biomarkers with the potential for clinical application. However, major limitations still exist. Although useful data on cancer genomics has accumulated rapidly, there has also been a simultaneous tendency for amplification of the complex relationships among the enormous number of variables that need to be considered. Disentangling these complex gene-gene interactions requires new approaches to data analysis to reveal information that has been obscured by traditional methods. Here, we review the current findings on biomarker identification in lung cancer, address their limitations and discuss some future directions for improvements in this area of research.     

Biomarkers for early diagnosis of pancreatic cancer

Pancreatic ductal adenocarcinoma is an aggressive malignancy with a 5-year survival rate of approximately 5%. The lack of established strategies for early detection contributes to this poor prognosis. Although several novel candidate biomarkers have been proposed for earlier diagnosis, none have been adopted into routine clinical use. In this review, the authors examine the challenges associated with finding new pancreatic cancer diagnostic biomarkers and explore why translation of biomarker research for patient benefit has thus far failed. The authors also review recent progress and highlight advances in the understanding of the biology of pancreatic cancer that may lead to improvements in biomarker detection and implementation.     

Biomarkers in heart failure: a clinical review

The diagnosis and management of heart failure remains challenging despite considerable clinical advances in recent decades. With greater understanding of the pathophysiology of this complex syndrome, a large number of candidate biomarkers have emerged and duly received scientific and clinical attention. These are frequently a measure of the degree of pathophysiological derangement or counter-regulatory processes occurring in heart failure and include biomarkers of neurohormonal activation, myocyte necrosis and myocardial remodelling amongst others. As such they may serve as an indicator of the presence, severity and possibly therapeutic response of the heart failure syndrome and may complement conventional clinical measurements and acumen. This may in turn lead to tangible clinical benefits and the targeting of intensified and often costly therapies to those most at risk. This article reviews and summarises the most extensively investigated biomarkers currently available, with an emphasis on clinical applicability and discusses the future evaluation of candidate biomarkers in patients with heart failure.     

老年肺癌的早期诊断进展

肺癌是目前世界范围内发病率和死亡率最高的恶性肿瘤。随着全球人口趋于老龄化,老年肺癌的发病率和病死率也在明显上升,且总体生存率差,早期诊断是改善其预后的关键。本文介绍了老年肺癌的诊断现状与进展,探讨了今后研究的方向。     

支气管镜新技术对肺癌的临床诊断研究进展

近年来先进的支气管镜技术在肺癌的诊断方面取得了突飞猛进的进展.支气管镜成像技术的方便快捷使其在临床上的应用越来越广.支气管镜技术的快速发展主要基于电子技术的进步,且越来越趋于小型化.如近年来逐渐应用于临床的自荧光成像、窄谱成像技术已并入支气管镜系统中应用于中央型肺癌的早期诊断.而新兴的光学显微成像技术如光学相干断层扫描、共聚焦激光显微内镜、细胞内镜的兴起有望在细胞学和组织学层面上观察肺部病变.另有超声支气管镜、导航支气管镜的应用为周围型肺癌的诊断找到了方向.这些支气管镜新技术为医务工作者提供了诊断肺癌的新思路.     

自荧光气管镜在支气管肺癌诊断中的临床应用

[目的]探讨自荧光气管镜(AFB)在支气管肺癌早期诊断中的价值.[方法]对198例临床怀疑支气管肺癌患者采用AFB联合白光气管镜(WLB)检查的诊断结果进行回顾性分析,将病理诊断为恶性肿瘤和不典型增生定义为阳性,正常黏膜、增生、慢性炎症定义为阴性,统计AFB与WLB镜下异常表现及病理结果,比较其对早期肺癌诊断的敏感度.[结果]198例中AFB表现异常者186例,WLB表现异常者133例,160例病理阳性结果中癌变黏膜156例,重度不典型增生4例.AFB发现异常病理证实癌变者156例,假阳性30例,敏感性97.5％,假阳性率16.1％,WLB发现异常病理证实者128例,假阳性5例,敏感性80.0％,假阳性率3.7％,两者在敏感性和假阳性率的差异均有统计学意义(P＜0.05).[结论]对于支气管内癌前病变和早期肺癌的定位诊断,AFB检查比WIB更加敏感.     

Biomarkers for systemic lupus erythematosus: a review and perspective

PURPOSE OF REVIEW: Despite decades of extensive work in the understanding of the etiopathogenesis of systemic lupus erythematosus, few biomarkers have been validated and widely accepted for this disease. The lack of reliable, specific biomarkers not only hampers clinical management of systemic lupus erythematosus but also impedes development of new therapeutic agents. This paper reviews briefly the historical aspects of systemic lupus erythematosus biomarkers and summarizes recent studies on candidate biomarkers. RECENT FINDINGS: Recognizing the urgent need for lupus biomarkers, a Lupus Biomarker Working Group has recently been initiated to facilitate collaborative efforts aimed at identifying and validating biomarkers for systemic lupus erythematosus. Based on available data, several laboratory markers have shown promise as biomarkers for susceptibility, diagnosis, and disease activity. These include Fc receptor genes (disease susceptibility), complement C4d-bound erythrocytes (diagnosis or disease activity), CD27 plasma cells (disease activity), 'interferon signature' (disease activity), and anti-C1q antibodies (disease activity and organ involvement). SUMMARY: There is a longstanding and recently rejuvenated enthusiasm for biomarkers that precisely and specifically reflect the pathophysiologic and clinical changes in systemic lupus erythematosus. Promising candidate biomarkers have been identified but must still be validated through rigorous, large-scale multicenter studies.     

肺癌的诊断进展

肺癌是全球最常见的恶性肿瘤之一，其死亡率位居恶性肿瘤首位。近年来肺癌发病率逐步升高，在我国，其发病率已由原恶性肿瘤的第6位跃居为第2位，在城市中死亡率占第一位，成为严重危害人类健康的杀手。     

Biomarkers in lung oncology

The survival of advanced non-small-cell lung cancer patients is short in spite of advances in new combination chemotherapy regimens. The benefit of adding antiangiogenic drugs and/or EGFR inhibitors is unclear. For the vast majority of patients without EGFR mutations, treatment approaches based on customization should be pursued. BRCA1 is central to the repair of DNA damage and is an important modulator of the differential effect of chemotherapy. Retrospective and prospective data indicate that low BRCA1 mRNA levels predict better response and survival when patients are treated with cisplatin, non-taxane combinations.For an important subgroup of patients with EGFR mutations, selective treatment with EGFR tyrosine kinase inhibitors is a major advance, with a dramatic impact on clinical outcomes. In a prospective study of customized erlotinib [1], overall response rate was 70% (including 12% complete responses), median progression free survival was 14 months (even longer in women and in patients with del 19), 20% of patients were disease-free at three years, and median survival was 27 months. Nonetheless, these clinical outcomes fall short of curability and continuous treatment with erlotinib or gefitinib is required. It is plausible that several genetically defined subclasses of EGFR mutations could help to improve current clinical outcomes by combining erlotinib or gefitinib with other targeted drugs.