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Genomic alterations that encourage stem cell activity and hinder proper maturation are central to the development of colorectal cancer (CRC). Key molecular mediators that promote these malignant properties require further elucidation to galvanize translational advances. We therefore aimed to characterize a key factor that blocks intestinal differentiation, define its transcriptional and epigenetic program, and provide preclinical evidence for therapeutic targeting in CRC. Intestinal tissue from transgenic mice and patients were analyzed by means of histopathology and immunostaining. Human CRC cells and neoplastic murine organoids were genetically manipulated for functional studies. Gene expression profiling was obtained through RNA sequencing. Histone modifications and transcription factor binding were determined with the use of chromatin immunoprecipitation sequencing. We demonstrate that SRY-box transcription factor 9 (SOX9) promotes CRC by activating a stem cell–like program that hinders intestinal differentiation. Intestinal adenomas and colorectal adenocarcinomas from mouse models and patients demonstrate ectopic and elevated expression of SOX9. Functional experiments indicate a requirement for SOX9 in human CRC cell lines and engineered neoplastic organoids. Disrupting SOX9 activity impairs primary CRC tumor growth by inducing intestinal differentiation. By binding to genome wide enhancers, SOX9 directly activates genes associated with Paneth and stem cell activity, including prominin 1 (PROM1). SOX9 up-regulates PROM1 via a Wnt-responsive intronic enhancer. A pentaspan transmembrane protein, PROM1 uses its first intracellular domain to support stem cell signaling, at least in part through SOX9, reinforcing a PROM1-SOX9 positive feedback loop. These studies establish SOX9 as a central regulator of an enhancer-driven stem cell–like program and carry important implications for developing therapeutics directed at overcoming differentiation defects in CRC. [Display omitted] The developmental transcription factor SOX9 engages genome-wide enhancers to activate a stem cell–like program that effectively blocks differentiation in colorectal cancer (CRC). Disrupting the PROM1-SOX9 axis induces intestinal differentiation and hinders CRC growth. [ABSTRACT FROM AUTHOR]

We studied the determinants of hemodynamics and analyzed the incidence, risk factors, and clinical impact of pulmonary homograft dysfunction following Ross surgery, after a 20-year follow-up at our referral center. From 1997 to 2017, a total of 142 patients underwent surgery using the Ross procedure. The development of moderate-severe stenosis (peak transhomograft pressure gradient 36 mm Hg or greater) and surgical or percutaneous Ross homograft reinterventions were evaluated by echocardiography in the immediate postoperative period and at annual intervals. After 20 years of follow-up, 31% of patients had moderate-severe homograft stenosis, and 9.1% had had to undergo one or two reinterventions, of which, six were valve replacements and seven were percutaneous interventions. At 1, 5, and 20 years, 89.4%, 74.6%, and 69% of these patients, respectively, were free from moderate-severe stenosis; and 99.3%, 95.7%, and 90.9%, respectively, had freedom from homograft reintervention. The pediatric group had a higher risk factor for homograft stenosis (hazard ratio 3.70; 95% confidence interval, 1.56 to 7.20, P =.002), whereas donor age behaved as a protective factor (hazard ratio 0.98; 95% confidence interval, 0.95 to 0.99; P =.044). Pulmonary homograft stenosis tended to appear in the first year (10.6%) or at 5 years (25.4%). Pulmonary homografts implanted in the Ross procedure offer satisfactory long-term results, but the level of homograft dysfunction is not negligible. Young recipient and donor age were associated with a higher rate of homograft stenosis during follow-up. Moreover, homograft dysfunction usually occurred during the first few years of follow-up, and may have been related to immune responses. [Display omitted] [ABSTRACT FROM AUTHOR]

• Stroke in the "hand knob area" is frequently misdiagnosed and confused with a peripheral pathology. • The prognosis will always depend on the involved stroke mechanism and the appropriate secondary prevention treatment. • The most prevalent stroke mechanism was cryptogenic, mainly embolic stroke of undetermined source. • The outcome was excellent regardless of stroke mechanism. Isolated hand paresis may reflect an infarction of the "hand knob area", which represents less than 1% of all ischemic strokes. In this type of stroke, a potential source of embolism is often identified. There are no large case series regarding this topic in Latin America. Herein we present the largest cohort of this entity in the region and we compare our results with those previously published. We analyzed all stroke patients admitted to our hospital between May 2015 – June 2018. Only patients with motor +/− sensory deficits restricted to the hand and ischemic stroke confirmed by MRI were included. We assessed stroke mechanism, clinical characteristics and outcome. From 339 patients admitted with ischemic stroke, 12 (3.53%) were included (9 men, 75%). Mean age: 60.4 years-old (range:24–79). Localization of stroke: 8 patients (66%) precentral gyrus, 3 (25%) postcentral; in 1 both gyri were affected. Stroke mechanism according to TOAST classification was as follows: two patients (16%) large artery atherosclerosis, two cardioembolic, one other determined etiology (thrombophilia), seven (58%) undetermined etiology (SUE). Nine patients (75%) received antiplatelets and statins, and three (25%) anticoagulants. The mean follow-up period was 11 months (range 1–26). Stroke recurrence was observed in one patient. At follow up, eight patients (66%) had a modified Rankin Score (mRS) of 0 and one a mRS of 1. In conclusion, in this series the most prevalent stroke mechanism was SUE, mainly embolic stroke of undetermined source. The outcome was excellent regardless of stroke mechanism. [ABSTRACT FROM AUTHOR]

Background: Fabry disease (FD) is an underdiagnosed cause of stroke in young adults, but the frequency of this association is largely unknown. We estimated the prevalence of FD in a nationwide cohort of young adults who had stroke and transient ischemic attack (TIA) in Argentina.Methods: This was a prospective, multicenter study of stroke and FD in young adults (18-55 years) conducted in Argentina between 2011 and 2015. Patients were enrolled if they had had a TIA or an ischemic or hemorrhagic stroke within the previous 180 days. FD was diagnosed by measuring α-galactosidase A activity (males) and through genetic studies (females).Results: We enrolled 311 patients (54% men, mean age: 41 years). Ischemic events occurred in 89% of patients (80% infarcts, 9% TIA) and hemorrhagic strokes in 11%. One female (.3% of the total group, 1% of the cryptogenic ischemic strokes) had the pathogenic mutation c.888G>A/p.Met296Ile /Exon 6 on the GAL gene. Her only other manifestation of FD was angiokeratoma. Eighteen females had nonpathogenic intronic variations: c.-10C>T, c.-12G>A, or both. Two patients had the nonpathogenic mutation D313Y, while a third had the likely benign mutation S126G.Conclusions: FD was identified in 1 patient (.3%) in this first Latin American study. The patient presented with a late-onset oligo-symptomatic form of the disease. A large number of nonpathogenic mutations were present in our cohort, and it is essential that they not be mistaken for pathogenic mutations to avoid unnecessary enzyme replacement treatment. [ABSTRACT FROM AUTHOR]

Copyright of Revista Española de Cardiología (18855857) is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Studies of the segmentation of the tourism markets have traditionally been undertaken by regression methods. The need to have a significant number of segments and qualifying variables has led, however, to the use of other procedures of multivariate analysis. CHAID (Chi-square Automatic Interaction Detection), which is more complex than other multivariate techniques, has rarely been used. This study applies the traditional methods of multivariate analysis and CHAID to the same population of tourists visiting a particular destination to compare the quality of the information obtained on tourism market segmentation. The results suggest that the analysis based on CHAID matches the nature of the problem studied better than those provided by discriminant analysis. [ABSTRACT FROM AUTHOR]

This work tries to evaluate road transport usage in Lanzarote Island and its implications for sustainable tourism development. The methodology followed here is the ecological footprint indicator. Its evaluation is based on projections of trip matrix estimated for Lanzarote Island. This study allows us to determine, in an approximate way, the environmental impact (that is, the contribution to climate change) of car usage on the island. Besides, it permits to extract some important conclusions about the trade-off existing between the need of individual mobility and tourism development in Lanzarote Island. [Copyright &y& Elsevier]

Abstract: This paper evaluates the influence of contracting out, or outsourcing, certain airport services and of commercial diversification strategy. Although most of the effort is being put towards applying non-parametric techniques in airport efficiency studies, we have chosen parametric methodology. We use a distance function, as it has known advantages. The findings show the positive contribution of outsourcing and non-aeronautical revenues on the efficiency of the Spanish airports'' network. [Copyright &y& Elsevier]

Abstract: This work analyses the level of service of Gran Canaria airport facilities as an approximation to evaluate the service quality given to tourism. Through a linear programming model we will determine the level of service established in a check-in service at this airport. The relevance of this parameter is related to the leisure time available for tourists in the airport terminal building. Therefore, it gives us an indirect measure of their perceived satisfaction of the service. [Copyright &y& Elsevier]

Abstract: The Canary Islands have an indisputable comparative and competitive edge within the European Union as regards their tourism products. The present study takes a segmented market approach to study the Canary Islands tourism market, featuring a range of tourism products, each of which satisfies to a greater or lesser extent the needs of one segment of demand. It has two objectives: firstly, to ascertain which segments of demand are currently acquired at destination and secondly, to identify within these segments the niches associated with the highest expenditure. This will enable us to draw up guideliness for a regional policy on product innovation that focuses on these niches and thus generates higher levels of local development. [Copyright &y& Elsevier]

Copyright of Revista Española de Cardiología (18855857) is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This paper attempts to analyse the productive efficiency of the airport industry. The analysis was carried out using the neoclassical approach of dual cost function. A translog joint cost function was used. Its flexibility enabled us to directly model the cost structure without imposing arbitrary a priori restrictions on the structure of production. Using the joint cost function, we ascertained the productive efficiency of the Spanish airport network. Through this work, we found evidence of possible inefficiencies related to the airport''s size. This aspect has some significant repercussions in the investment programme (airport planning) and its cost structure. [Copyright &y& Elsevier]

Tissue metaplasia is uncommon in adults because established cis -element programs resist rewiring. In Barrett's esophagus, the distal esophageal mucosa acquires a predominantly intestinal character, with notable gastric features, and is predisposed to developing invasive cancers. We sought to understand the chromatin underpinnings of Barrett's metaplasia and why it commonly displays simultaneous gastric and intestinal properties. We profiled cis -regulatory elements with active histone modifications in primary human biopsy materials using chromatin immunoprecipitation followed by DNA sequencing. Mutations in Barrett's esophagus were examined in relation to tissue-specific enhancer landscapes using a random forest machine-learning algorithm. We also profiled open chromatin at single-cell resolution in primary Barrett's biopsy specimens using the assay for transposase-accessible chromatin. We used 1- and 2-color immunohistochemistry to examine protein expression of tissue-restricted genes. Barrett's esophagus bears epigenome fingerprints of human stomach and intestinal columnar, but not esophageal squamous, epithelia. Mutational patterns were best explained as arising on the epigenome background of active gastric cis -elements, supporting the view that adjoining stomach epithelium is a likely tissue source. Individual cells in Barrett's metaplasia coexpress gastric and intestinal genes, reflecting concomitant chromatin access at enhancers ordinarily restricted to one or the other epithelium. Protein expression of stomach-specific mucins; CLDN18; and a novel gastric marker, ANXA10, showed extensive tissue and subclonal heterogeneity of dual stomach-intestinal cell states. These findings reveal mixed and dynamic tissue-restricted chromatin states and phenotypic heterogeneity in Barrett's esophagus. Pervasive intragland variation argues against stem-cell governance of this phenotype. [Display omitted] [ABSTRACT FROM AUTHOR]

A forensic source evaluation of polycyclic aromatic hydrocarbons (PAHs) in nearshore sediments in San Francisco Bay examined total PAH greater than ambient concentrations in sediments, and potential pyrogenic source relationships with respect to PAH compounds typically associated with point and nonpoint pyrogenic source types, including PAHs potentially associated with historical manufactured gas plant (MGP) operations. Diagnostic source ratio analysis was employed for determination of potential PAH source relationships. A two-model approach indicated distinct potential source signatures, as identified from the distributions of higher PAH concentrations in some sediments. Source characterization was aided by Polytopic Vector Analysis (PVA) and data visualization with t-Distributed Stochastic Neighbor Embedding (t-SNE). Two signatures exhibited pyrogenic character likely consistent with historical MGP sources, and one signature was related to creosote. A distinct and significant source of PAHs to the investigation area sediment consisted of ubiquitous nonpoint and potential unidentified point sources is termed "urban influence". • Forensic PAH diagnostic ratio evaluations defined potential point source signatures. • Signatures were consistent with historical MGP sources and urban influence. • PVA and t-SNE characterized potential MGP-related sources and urban influence. • PAH ratio-based source assignments correlated with PVA end-member assignments. [ABSTRACT FROM AUTHOR]

Introduction and Goal: There is scarce and contradictory data on B-cell lymphoma 2 (Bcl2), member of the Bcl-2 antiapoptotic molecules family of intrinsic apoptosis pathway, in ischemic stroke patients. The objective of this study was to determine whether there is an association between blood Bcl2 concentrations and mortality of ischemic stroke patients.Material and Methods: Five Intensive Care Units participated in this prospective and observational study of patients with severe malignant middle cerebral artery infarction (MMCAI). Severe MMCAI was diagnosed when acute infarction was present in 50% or more of said region and with a Glasgow Coma Scale (GCS) score of less than 9 points. Serum samples were collected at the time of MMCAI diagnosis.Findings: Higher serum Bcl2 concentrations (p = 0.001), lower platelet count (p = 0.01) and lower GCS (p = 0.002) were found in non-survivors (n = 28) than in MMCAI survivors (n = 28). Serum Bcl2 levels had an area under the curve for mortality prediction of 75% (95% CI = 62%-88%; p < 0.001). Patients with serum Bcl2 levels > 43.6 ng/mL had higher mortality rate according to Kaplan-Meier analysis (Hazard ratio=10.0; 95% CI = 3.4-29.5; p < 0.001). Multiple logistic regression showed an association between serum Bcl2 and mortality at 30 days (OR = 1.041; 95% CI = 1.006-1.077; p = 0.02) controlling for GCS and platelet count.Conclusions: This study reports for the first time the higher blood Bcl2 concentrations in non-surviving ischemic stroke patients than in survivors and the association between elevated blood Bcl2 and mortality in ischemic stroke patients. [ABSTRACT FROM AUTHOR]

Abstract: The long-term growth in the air transport is leading to the need to expand airport infrastructure but this has serious environmental implications. Thus, there is the need to establish an alternative to the traditional airport pricing structure for landing fees, which reflects the overall costs that air transport operators impose on others. Airport pricing should provide a sound guide for future investments, and at the same time reflect whether additional facilities are needed and at what price, by taking into account all costs, including environmental costs. This paper analyses one application of Ramsey Pricing on uncongested Spanish airport, by considering the CO2 emission costs as a valuable input. [Copyright &y& Elsevier]

Introduction and Goal: Substance P, a neuropeptide of the tachykinin family, is involved in the neuroinflammation of different diseases of the central nervous system. To our knowledge, there is no published data on the level of circulating substance P levels in the prognosis of patients with spontaneous intracerebral hemorrhage (ICH). Therefore, the objectives of this observational and prospective study were to determine whether serum substance P levels in ICH patients were associated with early mortality and whether could be used in the mortality prognostic.Material and Methods: We included patients with severe primary supratentorial ICH (defined as Glasgow Coma Scale < 9) from 6 Intensive Care Units of Spanish hospitals. We determined serum substance P levels at the time of severe ICH diagnosis, at fourth and at eighth day. Thirty-day mortality was considered the end-point study.Findings: Non-surviving (n=53) compared to surviving ICH patients (n=64) showed higher serum substance P levels at day 1 (p<0.001), day 4 (p<0.001) and day 8 (p<0.001). The area under the curve for 30-day mortality prediction by serum substance P levels was of 79% (95% CI = 70-86%; p<0.001). Kaplan-Meier analysis showed a higher 30-day mortality in patients with serum substance P levels>503 pg/mL (Hazard ratio=14.7; 95% CI=6.88-31.55; p<0.001). Multiple logistic regression analysis showed an association between serum substance P levels and 30-day mortality (Odds Ratio=1.006; 95% CI=1.002-1.010; p=0.004) controlling for ICH score, midline shift, glycemia, early evacuation of ICH.Conclusions: Thus, the novel aspects our study include that serum substance P levels in severe primary ICH patients were higher in non-surviving than in surviving patients, that serum substance P levels were associated with early mortality controlling for other variables, and that serum substance P levels could be used as biomarkers of prognosis. [ABSTRACT FROM AUTHOR]

Scarce data are available regarding the molecular mechanisms implicated in paclitaxel resistance. There is controversial data about β-tubulin mutations role in paclitaxel resistance. We have conducted this trial to address the influence of β-tubulin mutations in paclitaxel resistance in advanced non-small cell lung cancer (NSCLC). A group of 15 patients were biopsied and diagnosed of stages IIIB and IV NSCLC. Tumor specimens were used for DNA isolation and exon 4 of HM40 β-tubulin isotype was amplified and automatically sequenced, using both intronic and exonic primers. Next, the chemotherapy schedule consisted of weekly paclitaxel (100 or 150 mg/m2×6) followed 2 weeks later by cisplatin 100 mg/m2 on day 1, gemcitabine 1000 mg/m2 on days 1 and 14, and vinorelbine 25 mg/m2 on days 1 and 14, every 28 days. Using exonic primers, gene sequence alterations were found in 13/15 (87%) patients, including transitions (codons 180 and 182) and one silent transversion (codon 195). Also, three transversions (codons 231, 234, and 235) were found in all patients and controls. All alterations disappeared when sequenced with intronic primers. Our results suggest that point mutations demonstrated with exonic primers but not with intronic ones are probably due to β-tubulin pseudogenes present in advanced NSCLC specimens. Even so, when these β-tubulin pseudogenes are found there is a clear relation with clinical response. Although these changes could be relevant in paclitaxel resistance, this observation must be proven in future clinical trials to resolve “the tubulin dilemma”. [Copyright &y& Elsevier]

The combined analysis of the CCNH rs2230641 and the ABCG2 rs3114018 SNPs independently predict the development of severe oxaliplatin-induced peripheral neuropathy in early-stage colon cancer patients treated with oxaliplatin-based adjuvant chemotherapy. This pharmacogenetic approach might improve the stratification of patients, enabling specific dosing strategies and the assessment of potential neuroprotective therapies.Background Oxaliplatin-based chemotherapy (CT), widely used as adjuvant therapy for stage III and selected high-risk stage II colon cancer (CC) patients, is often associated with cumulative peripheral neuropathy. Our aim is to identify single-nucleotide polymorphisms (SNPs) in genes involved in oxaliplatin metabolism, DNA repair mechanisms, cell cycle control, detoxification or excretion pathways to predict severe (grade 2–3) oxaliplatin-induced peripheral neuropathy (OXPN) among CC patients treated with oxaliplatin and fluoropyrimidine-based adjuvant CT. Patients and methods Genomic DNA was extracted from formalin-fixed-paraffin-embedded peritumoral samples from 206 high-risk stage II and stage III CC patients receiving oxaliplatin-based adjuvant CT from January 2004 to December 2009. Genotyping was carried out for 34 SNPs in 15 genes using MassARRAY (SEQUENOM) technology. A total of 181 stage II–III CC patients treated with the same CT regimens were enrolled as a validation set. Results The rs2230641 cyclin H (CCNH) rs2230641 C/C [odd ratio (OR) = 5.03, 95% confidence interval (CI) 1.061–2.41, P = 0.042] and the ATP-binding cassette subfamily G, member 2 (ABCG2) rs3114018 A/A genotypes (OR = 2.67; 95% CI 0.95–4.41; P = 0.059) were associated with a higher risk of severe OXPN. In addition, patients harboring the combination of CCNH C/C and/or the ABCG2 rs3114018 A/A genotypes had a higher risk of grade 2–3 OXPN than those with the CCNH any T and ABCG2 any C genotypes (37.73% versus 19.42%; OR = 2.46; 95% CI 1.19–5.07; P = 0.014) in the logistic regression analysis using age, gender, adjuvant CT regimen and cumulative dose of oxaliplatin as covariates. The ability to predict severe OXPN of this combined analysis was independently validated in the second cohort (58% versus 33.33%; OR = 2.99; 95% CI 1.45–6.13; P = 0.002). Conclusions Our results suggest that SNPs in CCNH and ABCG2 can modulate the development of severe OXPN among stage II–III CC patients who received oxaliplatin-based CT, thus enabling the individualization of adjuvant treatment. [ABSTRACT FROM AUTHOR]

Treatment of non-small cell lung cancer (NSCLC) with cisplatin has a level of antitumor activity still modest. We have shown previously that MKP1/DUSP1 inhibits cisplatin-induced apoptosis in NSCLC cells and is overexpressed in tumors from most patients with stage I-II NSCLC. Here, using different NSCLC cell lines we found that MKP1 and NF-kappaB are differentially expressed. We studied whether targeting MKP1, NF-kappaB or both affects cisplatin-induced cell death. MKP1 is expressed in H460 and H727 cells. H727 and H1299 cells showed constitutive phosphorylation of Akt and increased NF-kappaB activity than did H460 cells. H460-MKP1-siRNA-expressing cells (but not H727-MKP1-siRNA or H1299-MKP1-siRNA cells) exhibit a marked increase in cisplatin response compared with parental cells. Treatment with the PI3K inhibitor LY294002 or the NF-kappaB inhibitor BAY11-7082 enhanced cisplatin antitumor activity in parental H1299 cells but only weakly affected responses of H727 and H460 cells. MKP1-siRNA expression enhanced the chemosensitization effect of LY294002 and BAY11-7082 on H727 and H460 cells. Additionally, NSCLC cell lines with higher NF-kappaB-constitutive activation were the most sensitive to PS-341 (Bortezomib), a non-specific NF-kappaB inhibitor. This finding suggests the proteasome as a suitable strategy in treating NSCLC tumors with high constitutive NF-kappaB activity. Altogether, these results showed that either an activated PI3K/Akt/NF-kappaB pathway and/or high MKP1 was linked to reduced sensitivity to cisplatin in NSCLC cells. Inhibition of NF-kappaB or PI3K potently enhanced cisplatin cytotoxicity in cells with endogenous or genetically induced low MKP1 levels. These findings support the potential improvement in cisplatin responses by co-targeting NF-kappaB or Akt and MKP1. [ABSTRACT FROM AUTHOR]

BACKGROUND: Adequate prognostic markers to predict outcome of patients with lung cancer are still needed. The aim of this study was to assess whether choline kinase alpha (ChoKalpha) gene expression could identify patients with different prognoses. ChoKalpha is an enzyme involved in cell metabolism and proliferation and has a role in oncogene-mediated transformation in several human tumours, including lung cancer. METHODS: 60 patients with non-small-cell lung cancer (NSCLC) who had undergone surgical resection in a single centre were enrolled into the study as the training group. We used real-time reverse-transcriptase PCR (RT-PCR) to measure ChoKalpha gene expression and analyse the association between ChoKalpha expression and survival in evaluable patients. Additionally, a second group of 120 patients with NSCLC from a different hospital were enrolled into the study as the validation group. We did an overall analysis of all 167 patients who had available tissue to confirm the cut-off point for future studies. The primary endpoints were lung-cancer-specific survival and relapse-free survival. FINDINGS: Seven of the 60 patients in the training group were not evaluable due to insufficient tissue. In the 53 evaluable patients, the cut-off for those with ChoKalpha overexpression was defined by receiver operator under the curve (ROC) methodology. 4-year lung-cancer-specific survival was 54.43% (95% CI 28.24-80.61) for 25 patients with ChoKalpha expression above the ROC-defined cut-off compared with 88.27% (75.79-100) for 28 patients with concentrations of the enzyme below this cut-off (hazard ratio [HR] 3.14 [0.83-11.88], p=0.07). In the validation group, six of the 120 enrolled patients were not evaluable due to insufficient tissue. For the other 114 patients, 4-year lung-cancer-specific survival was 46.66% (32.67-59.65) for those with ChoKalpha expression above the ROC-defined cut-off compared with 67.01% (50.92-81.11) for patients with concentrations of ChoKalpha below the cut-off (HR 1.87 [1.01-3.46], p=0.04). A global analysis of all 167 patients further confirmed the association between ChoKalpha overexpression and worse clinical outcome of patients with NSCLC: 4-year lung-cancer-specific survival for ChoKalpha expression above the ROC-defined cut-off was 49.00% (36.61-60.38) compared with 70.52% (59.80-76.75) for those with concentrations of ChoKalpha below the cut-off (HR 1.98 [1.14-3.45], p=0.01). The overall analysis confirmed the cut-off for ChoKalpha expression should be 1.91-times higher than concentrations noted in healthy tissues when ChoKalpha is used as an independent predictive factor of relapse-free and lung-cancer-specific survival in patients with early-stage NSCLC. INTERPRETATION: ChoKalpha expression is a new prognostic factor that could be used to help identify patients with early-stage NSCLC who might be at high risk of recurrence, and to identify patients with favourable prognosis who could receive less aggressive treatment options or avoid adjuvant systemic treatment. New treatments that inhibit ChoKalpha expression or activity in patients with lung cancer should be studied further. [ABSTRACT FROM AUTHOR]