BCAR4 Expression as a Predictive Biomarker for Endocrine Therapy Resistance in Breast Cancer.

BACKGROUND: Breast cancer, particularly the estrogen receptor positive (ER+) subtype, remains a leading cause of cancer-related death among women. Endocrine therapy is the most effective treatment for ER+ breast cancer; however, the development of resistance presents a significant challenge. This study explored the role of the breast cancer antiestrogen resistance 4 (BCAR4) gene as a potential driver of resistance and a pivotal biomarker in breast cancer. PATIENTS AND METHODS: The researchers undertook a comprehensive analysis of 1743 patients spanning 6 independent cohorts. They examined the association of BCAR4 expression with patient outcomes across all breast cancer types and the PAM50 molecular subtypes. The relationship between elevated BCAR4 expression and resistance to endocrine therapy including AIs, the prevailing standard-of-care for endocrine therapy, was also investigated. RESULTS: This meta-analysis corroborated the link between BCAR4 expression and adverse outcomes as well as resistance to endocrine therapy in breast cancer. Notably, BCAR4 expression is clinically significant in luminal A and B subtypes. Additionally, an association between BCAR4 expression and resistance to AI treatment was discerned. CONCLUSION: This study expands on previous findings by demonstrating that BCAR4 expression is associated with resistance to newer therapies. The identification of patients with intrinsic resistance to hormone therapy is crucial to avoid ineffective treatment strategies. These findings contribute to our understanding of endocrine therapy resistance in breast cancer and could potentially guide the development of more effective treatment strategies.

Effects of transfusing older red blood cells and platelets on obstetric patient outcomes: A retrospective cohort study.

OBJECTIVE: To investigate associations between transfusion of blood products close to the end of shelf-life and clinical outcomes in obstetric inpatients. METHODS: Mortality and morbidity were compared in patients transfused exclusively with red blood cells (RBC) stored for less than 21 days (fresh) versus RBC stored for 35 days or longer (old), and platelets (PLT) stored for 3 days or fewer (fresh) versus 4 days or longer (old) in Queensland, Australia from 2007 to 2013. Multivariable models were used to examine associations between these groups of blood products and clinical end points. RESULTS: There were 3371 patients who received RBC and 280 patients who received PLT of the eligible storage durations. Patients transfused with old RBC received fewer transfusions (2.7 ± 1.8 vs. 2.3 ± 1.0 units; P < 0.001). However, a higher rate of single-unit transfusions was also seen in those patients who exclusively received old RBC (252 [9.3%] vs. 92 [13.7%]; P = 0.003). Comparison of fresh vs. old blood products revealed no differences in the quantities of transfused RBC (9.5 ± 5.9 vs. 9.1 ± 5.2 units; P = 0.680) or PLT (1.5 ± 0.8 vs. 1.4 ± 1.1 units; P = 0.301) as well as the length of hospital stay for RBC (3 [2-5] vs. 3 [2-5] days; P = 0.124) or PLT (5 [4-8] vs. 6 [4-9] days; P = 0.120). CONCLUSION: Transfusing exclusively older RBC or PLT was not associated with increased morbidity or mortality.

Race and ethnicity in the COVID-19 Critical Care Consortium: demographics, treatments, and outcomes, an international observational registry study.

BACKGROUND: Improving access to healthcare for ethnic minorities is a public health priority in many countries, yet little is known about how to incorporate information on race, ethnicity, and related social determinants of health into large international studies. Most studies of differences in treatments and outcomes of COVID-19 associated with race and ethnicity are from single cities or countries. METHODS: We present the breadth of race and ethnicity reported for patients in the COVID-19 Critical Care Consortium, an international observational cohort study from 380 sites across 32 countries. Patients from the United States, Australia, and South Africa were the focus of an analysis of treatments and in-hospital mortality stratified by race and ethnicity. Inclusion criteria were admission to intensive care for acute COVID-19 between January 14th, 2020, and February 15, 2022. Measurements included demographics, comorbidities, disease severity scores, treatments for organ failure, and in-hospital mortality. RESULTS: Seven thousand three hundred ninety-four adults met the inclusion criteria. There was a wide variety of race and ethnicity designations. In the US, American Indian or Alaska Natives frequently received dialysis and mechanical ventilation and had the highest mortality. In Australia, organ failure scores were highest for Aboriginal/First Nations persons. The South Africa cohort ethnicities were predominantly Black African (50%) and Coloured* (28%). All patients in the South Africa cohort required mechanical ventilation. Mortality was highest for South Africa (68%), lowest for Australia (15%), and 30% in the US. CONCLUSIONS: Disease severity was higher for Indigenous ethnicity groups in the US and Australia than for other ethnicities. Race and ethnicity groups with longstanding healthcare disparities were found to have high acuity from COVID-19 and high mortality. Because there is no global system of race and ethnicity classification, researchers designing case report forms for international studies should consider including related information, such as socioeconomic status or migration background. *Note: "Coloured" is an official, contemporary government census category of South Africa and is a term of self-identification of race and ethnicity of many citizens of South Africa.

Vital signs-based deterioration prediction model assumptions can lead to losses in prediction performance.

OBJECTIVE: Vital signs-based models are complicated by repeated measures per patient and frequently missing data. This paper investigated the impacts of common vital signs modeling assumptions during clinical deterioration prediction model development. STUDY DESIGN AND SETTING: Electronic medical record (EMR) data from five Australian hospitals (1 January 2019-31 December 2020) were used. Summary statistics for each observation's prior vital signs were created. Missing data patterns were investigated using boosted decision trees, then imputed with common methods. Two example models predicting in-hospital mortality were developed, as follows: logistic regression and eXtreme Gradient Boosting. Model discrimination and calibration were assessed using the C-statistic and nonparametric calibration plots. RESULTS: The data contained 5,620,641 observations from 342,149 admissions. Missing vitals were associated with observation frequency, vital sign variability, and patient consciousness. Summary statistics improved discrimination slightly for logistic regression and markedly for eXtreme Gradient Boosting. Imputation method led to notable differences in model discrimination and calibration. Model calibration was generally poor. CONCLUSION: Summary statistics and imputation methods can improve model discrimination and reduce bias during model development, but it is questionable whether these differences are clinically significant. Researchers should consider why data are missing during model development and how this may impact clinical utility.

Hemorrhage, Disseminated Intravascular Coagulopathy, and Thrombosis Complications Among Critically Ill Patients with COVID-19: An International COVID-19 Critical Care Consortium Study.

OBJECTIVES: To determine the prevalence and outcomes associated with hemorrhage, disseminated intravascular coagulopathy, and thrombosis (HECTOR) complications in ICU patients with COVID-19. DESIGN: Prospective, observational study. SETTING: Two hundred twenty-nine ICUs across 32 countries. PATIENTS: Adult patients (≥ 16 yr) admitted to participating ICUs for severe COVID-19 from January 1, 2020, to December 31, 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: HECTOR complications occurred in 1,732 of 11,969 study eligible patients (14%). Acute thrombosis occurred in 1,249 patients (10%), including 712 (57%) with pulmonary embolism, 413 (33%) with myocardial ischemia, 93 (7.4%) with deep vein thrombosis, and 49 (3.9%) with ischemic strokes. Hemorrhagic complications were reported in 579 patients (4.8%), including 276 (48%) with gastrointestinal hemorrhage, 83 (14%) with hemorrhagic stroke, 77 (13%) with pulmonary hemorrhage, and 68 (12%) with hemorrhage associated with extracorporeal membrane oxygenation (ECMO) cannula site. Disseminated intravascular coagulation occurred in 11 patients (0.09%). Univariate analysis showed that diabetes, cardiac and kidney diseases, and ECMO use were risk factors for HECTOR. Among survivors, ICU stay was longer (median days 19 vs 12; p < 0.001) for patients with versus without HECTOR, but the hazard of ICU mortality was similar (hazard ratio [HR] 1.01; 95% CI 0.92-1.12; p = 0.784) overall, although this hazard was identified when non-ECMO patients were considered (HR 1.13; 95% CI 1.02-1.25; p = 0.015). Hemorrhagic complications were associated with an increased hazard of ICU mortality compared to patients without HECTOR complications (HR 1.26; 95% CI 1.09-1.45; p = 0.002), whereas thrombosis complications were associated with reduced hazard (HR 0.88; 95% CI 0.79-0.99, p = 0.03). CONCLUSIONS: HECTOR events are frequent complications of severe COVID-19 in ICU patients. Patients receiving ECMO are at particular risk of hemorrhagic complications. Hemorrhagic, but not thrombotic complications, are associated with increased ICU mortality.

The bias for statistical significance in sport and exercise medicine.

OBJECTIVES: We aimed to examine the bias for statistical significance using published confidence intervals in sport and exercise medicine research. DESIGN: Observational study. METHODS: The abstracts of 48,390 articles, published in 18 sports and exercise medicine journals between 2002 and 2022, were searched using a validated text-mining algorithm that identified and extracted ratio confidence intervals (odds, hazard, and risk ratios). The algorithm identified 1744 abstracts that included ratio confidence intervals, from which 4484 intervals were extracted. After excluding ineligible intervals, the analysis used 3819 intervals, reported as 95 % confidence intervals, from 1599 articles. The cumulative distributions of lower and upper confidence limits were plotted to identify any abnormal patterns, particularly around a ratio of 1 (the null hypothesis). The distributions were compared to those from unbiased reference data, which was not subjected to p-hacking or publication bias. A bias for statistical significance was further investigated using a histogram plot of z-values calculated from the extracted 95 % confidence intervals. RESULTS: There was a marked change in the cumulative distribution of lower and upper bound intervals just over and just under a ratio of 1. The bias for statistical significance was also clear in a stark under-representation of z-values between -1.96 and +1.96, corresponding to p-values above 0.05. CONCLUSIONS: There was an excess of published research with statistically significant results just below the standard significance threshold of 0.05, which is indicative of publication bias. Transparent research practices, including the use of registered reports, are needed to reduce the bias in published research.

Evaluating the costs and consequences of computerized clinical decision support systems in hospitals: a scoping review and recommendations for future practice.

OBJECTIVE: Sustainable investment in computerized decision support systems (CDSS) requires robust evaluation of their economic impacts compared with current clinical workflows. We reviewed current approaches used to evaluate the costs and consequences of CDSS in hospital settings and presented recommendations to improve the generalizability of future evaluations. MATERIALS AND METHODS: A scoping review of peer-reviewed research articles published since 2010. Searches were completed in the PubMed, Ovid Medline, Embase, and Scopus databases (last searched February 14, 2023). All studies reported the costs and consequences of a CDSS-based intervention compared with current hospital workflows. Findings were summarized using narrative synthesis. Individual studies were further appraised against the Consolidated Health Economic Evaluation and Reporting (CHEERS) 2022 checklist. RESULTS: Twenty-nine studies published since 2010 were included. Studies evaluated CDSS for adverse event surveillance (5 studies), antimicrobial stewardship (4 studies), blood product management (8 studies), laboratory testing (7 studies), and medication safety (5 studies). All studies evaluated costs from a hospital perspective but varied based on the valuation of resources affected by CDSS implementation, and the measurement of consequences. We recommend future studies follow guidance from the CHEERS checklist; use study designs that adjust for confounders; consider both the costs of CDSS implementation and adherence; evaluate consequences that are directly or indirectly affected by CDSS-initiated behavior change; examine the impacts of uncertainty and differences in outcomes across patient subgroups. DISCUSSION AND CONCLUSION: Improving consistency in the conduct and reporting of evaluations will enable detailed comparisons between promising initiatives, and their subsequent uptake by decision-makers.

Evaluation of an injury prevention programme (Prep-to-Play) in women and girls playing Australian Football: design of a pragmatic, type III, hybrid implementation-effectiveness, stepped-wedge, cluster randomised controlled trial.

INTRODUCTION: Due to the increase in participation and risk of anterior cruciate ligament (ACL) injuries and concussion in women's Australian Football, an injury prevention programme (Prep-to-Play) was codesigned with consumers (eg, coaches, players) and stakeholders (eg, the Australian Football League). The impact of supported and unsupported interventions on the use of Prep-to-Play (primary aim) and injury rates (secondary aim) will be evaluated in women and girls playing community Australian Football. METHODS AND ANALYSIS: This stepped-wedge, cluster randomised controlled trial will include ≥140 teams from U16, U18 or senior women's competitions. All 10 geographically separated clusters (each containing ≥14 teams) will start in the control (unsupported) phase and be randomised to one of five dates (or 'wedges') during the 2021 or 2022 season to sequentially transition to the intervention (supported Prep-to-Play), until all teams receive the intervention. Prep-to-Play includes four elements: a neuromuscular training warm-up, contact-focussed football skills (eg, tackling), strength exercises and education (eg, technique cues). When transitioning to supported interventions, study physiotherapists will deliver a workshop to coaches and player leaders on how to use Prep-to-Play, attend team training at least two times and provide ongoing support. In the unsupported phase, team will continue usual routines and may freely access available Prep-to-Play resources online (eg, posters and videos about the four elements), but without additional face-to-face support. Outcomes will be evaluated throughout the 2021 and 2022 seasons (~14 weeks per season). PRIMARY OUTCOME: use of Prep-to-Play will be reported via a team designate (weekly) and an independent observer (five visits over the two seasons) and defined as the team completing 75% of the programme, two-thirds (67%) of the time. SECONDARY OUTCOMES: injuries will be reported by the team sports trainer and/or players. Injury definition: any injury occurring during a football match or training that results in: (1) being unable to return to the field of play for that match or (2) missing ≥ one match. Outcomes in the supported and unsupported phases will be compared using a generalised linear mixed model adjusting for clustering and time. Due to the type III hybrid implementation-effectiveness design, the study is powered to detect a improvement in use of Prep-to-Play and a reduction in ACL injuries. ETHICS AND DISSEMINATION: La Trobe University Ethics Committee (HREC 20488) approved. Coaches provided informed consent to receive the supported intervention and players provided consent to be contacted if they sustained a head or knee injury. Results will be disseminated through partner organisations, peer-reviewed publications and scientific conferences. TRIAL REGISTRATION NUMBER: NCT04856241.

Pan-Cancer Analysis Reveals Recurrent BCAR4 Gene Fusions across Solid Tumors.

Chromosomal rearrangements often result in active regulatory regions juxtaposed upstream of an oncogene to generate an expressed gene fusion. Repeated activation of a common downstream partner-with differing upstream regions across a patient cohort-suggests a conserved oncogenic role. Analysis of 9,638 patients across 32 solid tumor types revealed an annotated long noncoding RNA (lncRNA), Breast Cancer Anti-Estrogen Resistance 4 (BCAR4), was the most prevalent, uncharacterized, downstream gene fusion partner occurring in 11 cancers. Its oncogenic role was confirmed using multiple cell lines with endogenous BCAR4 gene fusions. Furthermore, overexpressing clinically prevalent BCAR4 gene fusions in untransformed cell lines was sufficient to induce an oncogenic phenotype. We show that the minimum common region to all gene fusions harbors an open reading frame that is necessary to drive proliferation. IMPLICATIONS: BCAR4 gene fusions represent an underappreciated class of gene fusions that may have biological and clinical implications across solid tumors.

A scoping review of real-time automated clinical deterioration alerts and evidence of impacts on hospitalised patient outcomes.

BACKGROUND: Hospital patients experiencing clinical deterioration are at greater risk of adverse events. Monitoring patients through early warning systems is widespread, despite limited published evidence that they improve patient outcomes. Current limitations including infrequent or incorrect risk calculations may be mitigated by integration into electronic medical records. Our objective was to examine the impact on patient outcomes of systems for detecting and responding to real-time, automated alerts for clinical deterioration. METHODS: This review was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews checklist. We searched Medline, CINAHL and Embase for articles implementing real-time, automated deterioration alerts in hospitalised adults evaluating one or more patient outcomes including intensive care unit admission, length of stay, in-hospital cardiopulmonary arrest and in-hospital death. RESULTS: Of 639 studies identified, 18 were included in this review. Most studies did not report statistically significant associations between alert implementation and better patient outcomes. Four studies reported statistically significant improvements in two or more patient outcomes, and were the only studies to directly involve the patient's clinician. However, only one of these four studies was robust to existing trends in patient outcomes. Of the six studies using robust study designs, one reported a statistically significant improvement in patient outcomes; the rest did not detect differences. CONCLUSIONS: Most studies in this review did not detect improvements in patient outcomes following the implementation of real-time deterioration alerts. Future implementation studies should consider: directly involving the patient's physician or a dedicated surveillance nurse in structured response protocols for deteriorating patients; the workflow of alert recipients; and incorporating model features into the decision process to improve clinical utility.

LINC00355 regulates p27KIP expression by binding to MENIN to induce proliferation in late-stage relapse breast cancer.

Late-stage relapse (LSR) in patients with breast cancer (BC) occurs more than five years and up to 10 years after initial treatment and has less than 30% 5-year relative survival rate. Long non-coding RNAs (lncRNAs) play important roles in BC yet have not been studied in LSR BC. Here, we identify 1127 lncRNAs differentially expressed in LSR BC via transcriptome sequencing and analysis of 72 early-stage and 24 LSR BC patient tumors. Decreasing expression of the most up-regulated lncRNA, LINC00355, in BC and MCF7 long-term estrogen deprived cell lines decreases cellular invasion and proliferation. Subsequent mechanistic studies show that LINC00355 binds to MENIN and changes occupancy at the CDKN1B promoter to decrease p27Kip. In summary, this is a key study discovering lncRNAs in LSR BC and LINC00355 association with epigenetic regulation and proliferation in BC.

An observational analysis of the trope "A p-value of < 0.05 was considered statistically significant" and other cut-and-paste statistical methods.

Appropriate descriptions of statistical methods are essential for evaluating research quality and reproducibility. Despite continued efforts to improve reporting in publications, inadequate descriptions of statistical methods persist. At times, reading statistical methods sections can conjure feelings of dèjá vu, with content resembling cut-and-pasted or "boilerplate text" from already published work. Instances of boilerplate text suggest a mechanistic approach to statistical analysis, where the same default methods are being used and described using standardized text. To investigate the extent of this practice, we analyzed text extracted from published statistical methods sections from PLOS ONE and the Australian and New Zealand Clinical Trials Registry (ANZCTR). Topic modeling was applied to analyze data from 111,731 papers published in PLOS ONE and 9,523 studies registered with the ANZCTR. PLOS ONE topics emphasized definitions of statistical significance, software and descriptive statistics. One in three PLOS ONE papers contained at least 1 sentence that was a direct copy from another paper. 12,675 papers (11%) closely matched to the sentence "a p-value < 0.05 was considered statistically significant". Common topics across ANZCTR studies differentiated between study designs and analysis methods, with matching text found in approximately 3% of sections. Our findings quantify a serious problem affecting the reporting of statistical methods and shed light on perceptions about the communication of statistics as part of the scientific process. Results further emphasize the importance of rigorous statistical review to ensure that adequate descriptions of methods are prioritized over relatively minor details such as p-values and software when reporting research outcomes.

DANSR: A Tool for the Detection of Annotated and Novel Small RNAs.

Existing small noncoding RNA analysis tools are optimized for processing short sequencing reads (17-35 nucleotides) to monitor microRNA expression. However, these strategies under-represent many biologically relevant classes of small noncoding RNAs in the 36-200 nucleotides length range (tRNAs, snoRNAs, etc.). To address this, we developed DANSR, a tool for the detection of annotated and novel small RNAs using sequencing reads with variable lengths (ranging from 17-200 nt). While DANSR is broadly applicable to any small RNA dataset, we applied it to a cohort of matched normal, primary, and distant metastatic colorectal cancer specimens to demonstrate its ability to quantify annotated small RNAs, discover novel genes, and calculate differential expression. DANSR is available as an open source tool.

Estimating the costs of genomic sequencing in cancer control.

BACKGROUND: Despite the rapid uptake of genomic technologies within cancer care, few studies provide detailed information on the costs of sequencing across different applications. The objective of the study was to examine and categorise the complete costs involved in genomic sequencing for a range of applications within cancer settings. METHODS: We performed a cost-analysis using gross and micro-costing approaches for genomic sequencing performed during 2017/2018 across different settings in Brisbane, Australia. Sequencing was undertaken for patients with lung, breast, oesophageal cancers, melanoma or mesothelioma. Aggregated resource data were captured for a total of 1433 patients and point estimates of per patient costs were generated. Deterministic sensitivity analyses addressed the uncertainty in the estimates. Estimated costs to the public health system for resources were categorised into seven distinct activities in the sequencing process: sampling, extraction, library preparation, sequencing, analysis, data storage and clinical reporting. Costs were also aggregated according to labour, consumables, testing, equipment and 'other' categories. RESULTS: The per person costs were AU$347-429 (2018 US$240-297) for targeted panels, AU$871-$2788 (2018 US$604-1932) for exome sequencing, and AU$2895-4830 (2018 US$2006-3347) for whole genome sequencing. Cost proportions were highest for library preparation/sequencing materials (average 76.8% of total costs), sample extraction (8.1%), data analysis (9.2%) and data storage (2.6%). Capital costs for the sequencers were an additional AU$34-197 (2018 US$24-67) per person. CONCLUSIONS: Total costs were most sensitive to consumables and sequencing activities driven by commercial prices. Per person sequencing costs for cancer are high when tumour/blood pairs require testing. Using the natural steps involved in sequencing and categorising resources accordingly, future evaluations of costs or cost-effectiveness of clinical genomics across cancer projects could be more standardised and facilitate easier comparison of cost drivers.

Long non-coding RNA RAMS11 promotes metastatic colorectal cancer progression.

Colorectal cancer (CRC) is the most common gastrointestinal malignancy in the U.S.A. and approximately 50% of patients develop metastatic disease (mCRC). Despite our understanding of long non-coding RNAs (lncRNAs) in primary colon cancer, their role in mCRC and treatment resistance remains poorly characterized. Therefore, through transcriptome sequencing of normal, primary, and distant mCRC tissues we find 148 differentially expressed RNAs Associated with Metastasis (RAMS). We prioritize RAMS11 due to its association with poor disease-free survival and promotion of aggressive phenotypes in vitro and in vivo. A FDA-approved drug high-throughput viability assay shows that elevated RAMS11 expression increases resistance to topoisomerase inhibitors. Subsequent experiments demonstrate RAMS11-dependent recruitment of Chromobox protein 4 (CBX4) transcriptionally activates Topoisomerase II alpha (TOP2α). Overall, recent clinical trials using topoisomerase inhibitors coupled with our findings of RAMS11-dependent regulation of TOP2α supports the potential use of RAMS11 as a biomarker and therapeutic target for mCRC.

Evaluating bio-burden of frequently touched surfaces using Adenosine Triphosphate bioluminescence (ATP): Results from the Researching Effective Approaches to Cleaning in Hospitals (REACH) trial.

BACKGROUND: Environmental cleaning is an important approach to reducing healthcare-associated infection. The aim of this short research paper is to describe changes in the efficacy of post-discharge cleaning by examining the amount of bio-burden on frequent touch points (FTPs) in patient areas, using a validated Adenosine Triphosphate (ATP) bioluminescence sampling method. In so doing, we present findings from a secondary outcome of a recent trial, the Researching Effective Approaches to Cleaning in Hospitals (REACH) study. METHODS: The REACH study used a prospective, stepped-wedge randomised cluster design. Cross sectional ATP sampling was conducted at three of the 11 participating hospitals. At each hospital, during the control and intervention phase of the study, six Frequent Touch Points (FTPs) were sampled: toilet flush, bathroom tap, inside bathroom door handle, patient call button, over bed tray table, and bed rails. RESULTS: Across the three hospitals, 519 surfaces in 49 rooms (control phase) and 2856 surfaces in 251 rooms (intervention phase) were sampled. Bedroom FTP cleaning improved across all three hospitals. The cleaning of bathroom FTPs was generally high from the outset and remained consistent throughout the whole study period. Average cleaning outcomes for bathroom FTPs were consistently high during the control period however outcomes varied between individual FTP. Changes in cleaning performance over time reflected variation in intervention effectiveness at the hospital level. CONCLUSION: Findings confirm improvement in cleaning in the FTPs in bedrooms, demonstrating improvements in discharge cleaning aligned with the improvements seen when using fluorescent marking technology as a marker of performance.

Long non-coding RNA LCAL62 / LINC00261 is associated with lung adenocarcinoma prognosis.

BACKGROUND: More than half of non-small cell lung cancer (NSCLC) patients present with metastatic disease at initial diagnosis with an estimated five-year survival rate of ~5%. Despite advances in understanding primary lung cancer oncogenesis metastatic disease remains poorly characterized. Recent studies demonstrate important roles of long non-coding RNAs (lncRNAs) in tumor physiology and as prognostic markers. Therefore, we present the first transcriptome analysis to identify lncRNAs altered in metastatic lung adenocarcinoma leading to the discovery and characterization of the lncRNA LCAL62 as a prognostic biomarker. PATIENTS AND METHODS: RNA-Seq, microarray, nanoString expression, and clinical data from 1,116 LUAD patients across six independent cohorts and 83 LUAD cell lines were used to discover and evaluate the survival association of metastasis associated lncRNAs. Coexpression and gene set enrichment analyses were used to establish gene regulatory networks and implicate metastasis associated lncRNAs in specific biological processes. RESULTS: Our integrative analysis discovered LCAL62 as the most down-regulated lncRNA in metastasis. Further low LCAL62 expression promoted aggressive phenotypes and regulated genes associated with metastasis (such as metastasis repressor FOXA2). Low LCAL62 expression corresponded to poor overall patient survival across five independent lung adenocarcinoma cohorts (n = 881) including our own nanoString validation cohort. CONCLUSION: We discovered that LCAL62 was down-regulated in lung cancer progression to promote invasive phenotypes, and lower expression was significantly associated with poor patient outcome and aggressive lung adenocarcinoma.