Serum biomarkers provide valuable information about the diagnosis and prognosis of a wide variety of malignant tumors. Despite the identification of several useful serum biomarkers in lung cancer, ...consensus on their utility has not yet been reached. Furthermore, guidelines and standard protocols to implement their use for patients with lung cancer are lacking, despite the accumulation of much data on the efficacy of several serum biomarkers over recent decades. In this review, we discuss the molecular features, functions, and clinical relevance of the conventional serum biomarkers for lung cancer, including carcinoembryonic antigen (CEA), cytokeratin 19 fragment 21-1 (CYFRA 21-1), tissue polypeptide antigen (TPA), carbohydrate antigen 19-9 (CA19-9), sialyl Lewis
x
(sLe
x
), carbohydrate antigen 125 (CA-125), squamous cell carcinoma-related antigen (SCC-Ag), neuron-specific enolase (NSE), and pro-gastrin-releasing peptide (proGRP), aiming to provide a snapshot of the current landscape and their potential combined utility in the diagnosis and prognosis of lung cancer.
The four major histological types of lung cancer are adenocarcinoma, squamous cell carcinoma (SQ), large cell carcinoma and small cell carcinoma. Over the past few decades, the incidence of lung ...adenocarcinoma has increased gradually in most countries as the most frequently occurring histological type, displacing SQ. Adenocarcinoma is the predominant type of lung cancer among lifelong non-smokers and among females. Especially in East Asian countries, the cause(s) of the increase in adenocarcinomas are not clear. Several genetic mutations specific to lung adenocarcinomas have been found, representing attractive targets for molecular therapy. Recently, the pathological classification of lung adenocarcinoma was revised by integrating the newer clinical and biological knowledge concerning this prevailing type. Additional epidemiological, pathological and genetic studies are required to better understand this type of lung cancer.
Lung cancer and related diseases have been one of the most common causes of deaths worldwide. Genomic-based biomarkers may hardly reflect the underlying dynamic molecular mechanism of functional ...protein interactions, which is the center of a disease. Recent developments in mass spectrometry (MS) have made it possible to analyze disease-relevant proteins expressed in clinical specimens by proteomic challenges. Areas covered: To understand the molecular mechanisms of lung cancer and its subtypes, chronic obstructive pulmonary disease (COPD), asthma and others, great efforts have been taken to identify numerous relevant proteins by MS-based clinical proteomic approaches. Since lung cancer is a multifactorial disease that is biologically associated with asthma and COPD among various lung diseases, this study focused on proteomic studies on biomarker discovery using various clinical specimens for lung cancer, COPD, and asthma. Expert commentary: MS-based exploratory proteomics utilizing clinical specimens, which can incorporate both experimental and bioinformatic analysis of protein-protein interaction and also can adopt proteogenomic approaches, makes it possible to reveal molecular networks that are relevant to a disease subgroup and that could differentiate between drug responders and non-responders, good and poor prognoses, drug resistance, and so on.
Bicruciate-retaining (BCR) prosthesis has been introduced to recreate normal knee movement by preserving both the anterior and posterior cruciate ligaments. However, the use of BCR total knee ...arthroplasty (TKA) is still debatable because of several disappointing reports. We have been performing BCR TKAs with personalized alignment (PA). This study aimed to reveal the limb alignment and soft tissue balance of FA-BCR TKAs and compare the clinical outcomes of FA-BCR TKAs with those of unicompartmental knee arthroplasty (UKA).
Fifty BCR TKAs and 58 UKAs were included in this study. The joint component gaps of BCR TKA were evaluated intraoperatively and the postoperative hip-knee-ankle (HKA) angle, medial proximal tibial angle (MPTA), and lateral distal femoral angle (LDFA) were measured using full-length standing radiography. The short-term clinical outcomes of BCR TKAs were compared with those of UKA using the scoring system of 2011 Knee Society Scoring (KSS) and the knee injury and osteoarthritis outcome score (KOOS) at an average of 2 years postoperatively (1-4yeras).
The coronal alignment values of PA-BCR TKA were as follows: HKA angle, 177.9° ± 2.3°; MPTA, 85.4° ± 1.9°; and LDFA, 87.5° ± 1.9°. The joint component gaps at flexion angles of 10°, 30°, 60°, and 90° were 11.1 ± 1.2, 10.9 ± 1.4, 10.7 ± 1.3, and 11.2 ± 1.4 mm for the medial compartment and 12.9 ± 1.5, 12.6 ± 1.8, 12.5 ± 1.8 and 12.5 ± 1.7 mm for the lateral compartment, respectively. The patient expectation score and maximum extension angle of PA-BCR TKA were significantly better than those of UKAs.
The short-term clinical outcomes of PA-BCR TKA were comparable or a slightly superior to those of UKAs.
In 2011, a new pathological classification of lung adenocarcinoma was proposed by the International Association for the Study of Lung Cancer, the American Thoracic Society and the European ...Respiratory Society. The new criteria classify adenocarcinomas into eight subtypes according to their histological features. The criteria introduce a new concept of early stage lung cancer, consisting of adenocarcinoma in situ and minimally invasive adenocarcinoma, and categorize invasive adenocarcinomas by the predominant histological pattern. In addition to morphological differences among subtypes, the classification also considers the tumor behavior based on the genetic background within each subtype. We herein review the clinical impact of this new classification for chest surgeons based on the data from several recent validation studies from various institutions.
Small-cell lung carcinoma (SCLC) and large-cell neuroendocrine lung carcinoma (LCNEC) are high-grade lung neuroendocrine tumors (NET). However, comparative protein expression within SCLC and LCNEC ...remains unclear. Here, protein expression profiles were obtained via mass spectrometry-based proteomic analysis. Weighted gene co-expression network analysis (WGCNA) identified co-expressed modules and hub genes. Of 34 identified modules, six were significant and selected for protein-protein interaction (PPI) network analysis and pathway enrichment. Within the six modules, the activation of cellular processes and complexes, such as alternative mRNA splicing, translation initiation, nucleosome remodeling and deacetylase (NuRD) complex, SWItch/Sucrose Non-Fermentable (SWI/SNF) superfamily-type complex, chromatin remodeling pathway, and mRNA metabolic processes, were significant to SCLC. Modules enriched in processes, including signal recognition particle (SRP)-dependent co-translational protein targeting to membrane, nuclear-transcribed mRNA catabolic process of nonsense-mediated decay (NMD), and cellular macromolecule catabolic process, were characteristically activated in LCNEC. Novel high-degree hub genes were identified for each module. Master and upstream regulators were predicted via causal network analysis. This study provides an understanding of the molecular differences in tumorigenesis and malignancy between SCLC and LCNEC and may help identify potential therapeutic targets.
Solid-predominant lung adenocarcinoma (SPA), which is one of the high-risk subtypes with poor prognosis and unsatisfactory response to chemotherapy and targeted therapy in lung adenocarcinoma, ...remains molecular profile unclarified. Weighted correlation network analysis (WGCNA) was used for data mining, especially for studying biological networks based on pairwise correlations between variables. This study aimed to identify disease-related protein co-expression networks associated with early-stage SPA.
We assessed cancerous cells laser-microdissected from formalin-fixed paraffin-embedded (FFPE) tissues of a SPA group (
= 5), referencing a low-risk subtype, a lepidic predominant subtype group (LPA) (
= 4), and another high-risk subtype, micropapillary predominant subtype (MPA) group (
= 3) and performed mass spectrometry-based proteomic analysis. Disease-related co-expression networks associated with the SPA subtype were identified by WGCNA and their upstream regulators and causal networks were predicted by Ingenuity Pathway Analysis.
Among the forty WGCNA network modules identified, two network modules were found to be associated significantly with the SPA subtype. Canonical enriched pathways were highly associated with cellular growth, proliferation, and immune response. Upregulated HLA class I molecules HLA-G and HLA-B implicated high mutation burden and T cell activation in the SPA subtype. Upstream analysis implicated the involvement of highly activated oncogenic regulators, MYC, MLXIPL, MYCN, the redox master regulator NFE2L2, and the highly inhibited LARP1, leading to oncogenic IRES-dependent translation, and also regulators of the adaptive immune response, including highly activated IFNG, TCRD, CD3-TCR, CD8A, CD8B, CD3, CD80/CD86, and highly inhibited LILRB2. Interestingly, the immune checkpoint molecule HLA-G, which is the counterpart of LILRB2, was highly expressed characteristically in the SPA subtype and might be associated with antitumor immunity.
Our findings provide a disease molecular profile based on protein co-expression networks identified for the high-risk solid predominant adenocarcinoma, which will help develop future therapeutic strategies.
No therapeutic targets have been identified for lung squamous cell cancer (SqCC) which is the second most prevalent lung cancer because its molecular profiles remain unclear. This study aimed to ...unveil disease-related protein networks by proteomic and bioinformatic assessment of laser-microdissected cancerous cells from seven SqCCs compared with eight representative lung adenocarcinomas. We identified three network modules significant to lung SqCC using weighted gene co-expression network analysis. One module was intrinsically annotated to keratinization and cell proliferation of SqCC, accompanied by hypoxia-induced aerobic glycolysis, in which key regulators were activated (HIF1A, ROCK2, EFNA1-5) and highly suppressed (KMT2D). The other two modules were significant for translational initiation, nonsense-mediated mRNA decay, inhibited cell death, and interestingly, eIF2 signaling, in which key regulators, MYC and MLXIPL, were highly activated. Another key regulator LARP1, the master regulator in cap-dependent translation, was highly suppressed although upregulations were observed for hub proteins including EIF3F and LARP1 targeted ribosomal proteins, among which PS25 is the key ribosomal protein in IRES-dependent translation. Our results suggest an underlying progression mechanism largely caused by switching to the cap-independent, IRES-dependent translation of mRNA subsets encoding oncogenic proteins. Our findings may help to develop therapeutic strategies to improve patient outcomes.
Purpose: It is not clear whether women with non-small-cell lung cancer (NSCLC) live significantly longer than men. Thus, we conducted a meta-analysis of published studies to quantitatively compare ...NSCLC survival data between genders. Materials and Methods: A MEDLINE Web search for computer-archived bibliographic data regarding overall survival differences between genders was performed. DerSimonian-Laird random effects analysis was used to estimate the pooled hazard ratio (HR). Results: We selected 39 articles as appropriate data sources, involving 86 800 patients including 32 701 women and 54 099 men. Combined HRs for women vs. men in studies using univariate and multivariate analyses respectively were 0.79 (p <0.0001) and 0.78 (p <0.0001). Pooled HRs for 3 study subgroups having (1) fewer than 30% stage I cases, (2) fewer than 50% adenocarcinoma cases, and (3) statistical adjustment for smoking status all indicated the survival advantage of women. Conclusion: This meta-analysis of published data concerning NSCLC patients indicated significantly better survival for women.
PurposeTo compare the degree of medial meniscal extrusion (MME) between knees with medial meniscus posterior root tear (MMPRT) and degenerative tears of the medial meniscus using ultrasonography (US) ...in different limb positions and to identify the findings characteristic of MMPRT.MethodsThe study group comprised 25 subjects with MMPRT (group RT), 25 subjects with degenerative medial meniscal tears (group D), and 25 knees with no abnormalities of the medial meniscus (MM) on magnetic resonance imaging (MRI) (group C) whose age was ≥40 years. MME was evaluated using US in the supine, figure-4, feet-dangling, and standing positions. The MME was evaluated by the actual measurement values and the relative values to the MME in the supine position. The differences in the MME among the 3 groups in each limb position were analyzed using one-way analysis of variance. P < .05 was considered significant.ResultsThe actual MME values were largest in group RT in all 4 limb positions. When changing the limb position from the supine to the figure-4, the actual MME increased from 3.8 ± 0.8 mm to 5.5 ± 1.3 mm in group RT, whereas it decreased from 3.4 ± 1.1 mm to 1.8 ± 1.2 mm in group D, showing the most significant difference in MME of the figure-4 position between the 2 groups (P < .001). In group RT, 88% of knees had the maximum MME in the figure-4 position. In group D, 60% of knees had the maximum MME in the standing position and only 2 knees (8%) had the maximum MME in the figure-4 position.ConclusionsThe increase in MME from the supine to the figure-4 position was a characteristic finding of MMPRT but not degenerative tears.Level of EvidenceLevel III, case-control study.
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