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Journal of the National Cancer Institute Aug 2018The Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK) were developed to address widespread deficiencies in the reporting of such studies. The REMARK... (Review)
Review
The Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK) were developed to address widespread deficiencies in the reporting of such studies. The REMARK checklist consists of 20 items to report for published tumor marker prognostic studies. A detailed paper was published explaining the rationale behind checklist items, providing positive examples and giving empirical evidence of the quality of reporting. REMARK provides a comprehensive overview to educate on good reporting and provide a valuable reference for the many issues to consider when designing, conducting, and analyzing tumor marker studies and prognostic studies in medicine in general. Despite support for REMARK from major cancer journals, prognostic factor research studies remain poorly reported. To encourage dissemination and uptake of REMARK, we have produced this considerably abridged version of the detailed explanatory manuscript, which may also serve as a brief guide to key issues for investigators planning tumor marker prognostic studies. To summarize the current situation, more recent papers investigating the quality of reporting and related reporting guidelines are cited, but otherwise the literature is not updated. Another important impetus for this paper is that it serves as a basis for literal translations into other languages. Translations will help to bring key information to a larger audience world-wide. Many more details can be found in the original paper.
Topics: Biomarkers, Tumor; Biomedical Research; Humans; Neoplasms; Practice Guidelines as Topic; Prognosis; Publishing; Research Design
PubMed: 29873743
DOI: 10.1093/jnci/djy088 -
The Oncologist May 2022Circulating biomarkers have emerged as valuable surrogates for evaluating disease states in solid malignancies. Their relative ease of access and rapid turnover has... (Review)
Review
Circulating biomarkers have emerged as valuable surrogates for evaluating disease states in solid malignancies. Their relative ease of access and rapid turnover has bolstered clinical applications in monitoring treatment efficacy and cancer progression. In this review, the roles of various circulating biomarkers in monitoring treatment response are described. Non-specific markers of disease burden, tumor markers (eg CA 125, CEA, PSA, etc.), circulating tumor cells, nucleic acids, exosomes, and metabolomic arrays are highlighted. Specifically, the discovery of each of these markers is reviewed, with examples illustrating their use in influencing treatment decisions, and barriers to their application noted where these exist. Finally, opportunities for future work using these circulating biomarkers are discussed.
Topics: Antineoplastic Agents; Biomarkers, Tumor; Exosomes; Humans; Neoplastic Cells, Circulating
PubMed: 35285488
DOI: 10.1093/oncolo/oyac047 -
Cancer Control : Journal of the Moffitt... 2023Tumor markers (TMs) are important for the prognosis of gastric cancer (GC). However, the prognostic importance of the tumor marker index (TMI) based on GC-specific TMs...
BACKGROUND
Tumor markers (TMs) are important for the prognosis of gastric cancer (GC). However, the prognostic importance of the tumor marker index (TMI) based on GC-specific TMs for advanced gastric cancer (AGC) still needs to be further explored.
METHODS
We retrospectively examined patients who underwent radical gastric cancer surgery between February 2014 and June 2016 at the Department of Gastroenterological Surgery, Affiliated Cancer Hospital, Harbin Medical University. The patients were divided into training and validation groups. TMI was determined as the geometric mean of the standard cancer antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) levels. Patient overall survival was assessed using the Kaplan-Meier method. Independent prognosis-associated risk factors were identified using Cox hazard regression models. A nomogram model incorporating TMI and clinicopathological factors was developed, and its performance was evaluated using a decision curve analysis, concordance index, and calibration plots.
RESULTS
In the TMI training cohort, the cutoff value was set at .439, categorizing patients into TMI-High and TMI-Low groups. The 5-year survival rate in the TMI-Low group significantly surpassed that in the TMI-High group (78.2% vs 58.1% and 49.7 vs 41.6, < .001). TMI emerged as an independent prognostic factor. The nomogram accurately predicted patient prognosis by using TMI and clinicopathological characteristics. Validation of the TMI in the independent cohort yielded satisfactory results.
CONCLUSION
The TMI constructed based on specific TMs associated with gastric cancer can offer a precise prognostic prediction for patients.
Topics: Humans; Biomarkers, Tumor; Stomach Neoplasms; Neoplasm Staging; Retrospective Studies; Prognosis
PubMed: 37728233
DOI: 10.1177/10732748231202466 -
Clinical Chemistry and Laboratory... Mar 2022Biological variation data (BV) can be used for different applications, but this depends on the availability of robust and relevant BV data. In this study, we aimed to... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Biological variation data (BV) can be used for different applications, but this depends on the availability of robust and relevant BV data. In this study, we aimed to summarize and appraise BV studies for tumor markers, to examine the influence of study population characteristics and concentrations on BV estimates and to discuss the applicability of BV data for tumor markers in clinical practice.
METHODS
Studies reporting BV data for tumor markers related to gastrointestinal, prostate, breast, ovarian, haematological, lung, and dermatological cancers were identified by a systematic literature search. Relevant studies were evaluated by the Biological Variation Data Critical Appraisal Checklist (BIVAC) and meta-analyses were performed for BIVAC compliant studies to deliver global estimates of within-subject (CV) and between-subject (CV) BV with 95% CI.
RESULTS
The systematic review identified 49 studies delivering results for 22 tumor markers; four papers received BIVAC grade A, 3 B, 27 C and 15 D. Out of these, 29 CV and 29 CV estimates met the criteria to be included in the meta-analysis. Robust data are lacking to conclude on the relationship between BV and different disease states and tumor marker concentrations.
CONCLUSIONS
This review identifies a lack of high-quality BV studies for many tumor markers and a need for delivery of BIVAC compliant studies, including in different disease states and tumor marker concentrations. As of yet, the state-of-the-art may still be the most appropriate model to establish analytical performance specifications for the majority of tumor markers.
Topics: Biomarkers, Tumor; Checklist; Humans; Male
PubMed: 35143717
DOI: 10.1515/cclm-2021-0725 -
Tumour Biology : the Journal of the... 2024Clinical laboratories are responsible for performing lung cancer tumor marker testing as part of routine clinical care. It is their responsibility to guarantee that...
Clinical laboratories are responsible for performing lung cancer tumor marker testing as part of routine clinical care. It is their responsibility to guarantee that the reported tumor marker results are reliable and meet the necessary quality standards for proper clinical use. During the different laboratory phases, pre-analytical, analytical and post-analytical, specific steps and processes can introduce errors and generate incorrect clinical interpretation. This editorial briefly outlines critical laboratory issues related to lung cancer tumor markers, specific for each of these three laboratory phases.
Topics: Humans; Laboratories, Clinical; Lung Neoplasms; Laboratories; Biomarkers, Tumor
PubMed: 38517828
DOI: 10.3233/TUB-240005 -
Molecules (Basel, Switzerland) Oct 2022Cancer is a leading cause of death worldwide, with an increasing mortality rate over the past years. The early detection of cancer contributes to early diagnosis and... (Review)
Review
Cancer is a leading cause of death worldwide, with an increasing mortality rate over the past years. The early detection of cancer contributes to early diagnosis and subsequent treatment. How to detect early cancer has become one of the hot research directions of cancer. Tumor biomarkers, biochemical parameters for reflecting cancer occurrence and progression have caused much attention in cancer early detection. Due to high sensitivity, convenience and low cost, biosensors have been largely developed to detect tumor biomarkers. This review describes the application of various biosensors in detecting tumor markers. Firstly, several typical tumor makers, such as neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), prostate-specific antigen (PSA), squamous cell carcinoma antigen (SCCA), carbohydrate, antigen19-9 (CA19-9) and tumor suppressor p53 (TP53), which may be helpful for early cancer detection in the clinic, are briefly described. Then, various biosensors, mainly focusing on electrochemical biosensors, optical biosensors, photoelectrochemical biosensors, piezoelectric biosensors and aptamer sensors, are discussed. Specifically, the operation principles of biosensors, nanomaterials used in biosensors and the application of biosensors in tumor marker detection have been comprehensively reviewed and provided. Lastly, the challenges and prospects for developing effective biosensors for early cancer diagnosis are discussed.
Topics: Male; Humans; Biomarkers, Tumor; Biosensing Techniques; Nanostructures; Early Detection of Cancer; Neoplasms; Biomarkers
PubMed: 36364157
DOI: 10.3390/molecules27217327 -
Annals of the New York Academy of... Dec 2018Technological progress within the last 15-20 years has significantly increased our knowledge about the molecular basis of cancer development, tumor progression, and... (Review)
Review
Technological progress within the last 15-20 years has significantly increased our knowledge about the molecular basis of cancer development, tumor progression, and treatment response. As a consequence, a vast number of biomarkers have been proposed, but only a small fraction of them have found their way into clinical use. The aim of this paper is to describe the specific demands a clinically relevant biomarker should meet and how biomarkers can be tested stepwise. We name this procedure the "triple-R principle": robustness, reproducibility, and relevance. The usefulness of this principle is illustrated with the marker TP53. Since it is mutated in a broad spectrum of cancer entities, TP53 can be considered a very promising marker. Thus, TP53 has been studied in detail but there is still no explicit consensus about its clinical value. By considering our own experience and reviewing the literature, we demonstrate that a major problem of current biomarker research is disregard of whether the biomarker is prognostic or predictive. As an example, it is demonstrated that TP53 is not a prognostic marker, but rather a purely predictive marker, and that disregard of this fact has made this otherwise strong biomarker appear as not being clinically useful so far.
Topics: Biomarkers, Tumor; Humans; Neoplasms; Prognosis; Tumor Suppressor Protein p53
PubMed: 30112858
DOI: 10.1111/nyas.13947 -
International Journal of Molecular... Jun 2021Preclinical drug development studies rarely consider the impact of a candidate drug on established metastatic disease. This may explain why agents that are successful in...
BACKGROUND
Preclinical drug development studies rarely consider the impact of a candidate drug on established metastatic disease. This may explain why agents that are successful in subcutaneous and even orthotopic preclinical models often fail to demonstrate efficacy in clinical trials. It is reasonable to anticipate that sites of metastasis will be phenotypically unique, as each tumor will have evolved heterogeneously with respect to gene expression as well as the associated phenotypic outcome of that expression. The objective for the studies described here was to gain an understanding of the tumor heterogeneity that exists in established metastatic disease and use this information to define a preclinical model that is more predictive of treatment outcome when testing novel drug candidates clinically.
METHODS
Female NCr nude mice were inoculated with fluorescent (mKate), Her2/neu-positive human breast cancer cells (JIMT-mKate), either in the mammary fat pad (orthotopic; OT) to replicate a primary tumor, or directly into the left ventricle (intracardiac; IC), where cells eventually localize in multiple sites to create a model of established metastasis. Tumor development was monitored by in vivo fluorescence imaging (IVFI). Subsequently, animals were sacrificed, and tumor tissues were isolated and imaged ex vivo. Tumors within organ tissues were further analyzed via multiplex immunohistochemistry (mIHC) for Her2/neu expression, blood vessels (CD31), as well as a nuclear marker (Hoechst) and fluorescence (mKate) expressed by the tumor cells.
RESULTS
Following IC injection, JIMT-1mKate cells consistently formed tumors in the lung, liver, brain, kidney, ovaries, and adrenal glands. Disseminated tumors were highly variable when assessing vessel density (CD31) and tumor marker expression (mkate, Her2/neu). Interestingly, tumors which developed within an organ did not adopt a vessel microarchitecture that mimicked the organ where growth occurred, nor did the vessel microarchitecture appear comparable to the primary tumor. Rather, metastatic lesions showed considerable variability, suggesting that each secondary tumor is a distinct disease entity from a microenvironmental perspective.
CONCLUSIONS
The data indicate that more phenotypic heterogeneity in the tumor microenvironment exists in models of metastatic disease than has been previously appreciated, and this heterogeneity may better reflect the metastatic cancer in patients typically enrolled in early-stage Phase I/II clinical trials. Similar to the suggestion of others in the past, the use of models of established metastasis preclinically should be required as part of the anticancer drug candidate development process, and this may be particularly important for targeted therapeutics and/or nanotherapeutics.
Topics: Animals; Biomarkers, Tumor; Brain; Cell Line, Tumor; Disease Models, Animal; Female; Lung; Mice, Nude; Neoplasm Metastasis; Tumor Microenvironment; Mice
PubMed: 34199298
DOI: 10.3390/ijms22126336 -
Urologic Oncology Jan 2019We previously reported that elevated precystectomy serum levels of epithelial tumor markers predict worse oncological outcome in patients with invasive bladder cancer... (Review)
Review
INTRODUCTION AND OBJECTIVES
We previously reported that elevated precystectomy serum levels of epithelial tumor markers predict worse oncological outcome in patients with invasive bladder cancer (BC). Herein, we evaluated the effect of neoadjuvant chemotherapy (NAC) on elevated tumor marker levels and their association with oncological outcomes.
METHODS
Under IRB approval, serum levels of Carbohydrate Antigen 125 (CA-125), Carbohydrate Antigen 19-9 (CA 19-9) and Carcinoembryonic Antigen (CEA) were prospectively measured in 480 patients with invasive BC from August 2011 through December 2016. In the subgroup undergoing NAC, markers were measured prior to the first and after the last cycle of chemotherapy (prior to cystectomy).
RESULTS
Three hundred and thirty-seven patients were eligible for the study, with a median age was 71 years (range 34-93) and 81% (272) male. Elevated precystectomy level of any tumor markers (31% of patients) was independently associated with worse recurrence-free survival (hazard ratio [HR] = 2.81; P < 0.001) and overall survival (HR = 3.97; P < 0.001). One hundred and twenty-five (37%) patients underwent NAC, of whom 59 had a complete tumor marker profile and 30 (51%) had an elevated pre-NAC tumor marker. Following completion of chemotherapy, 10/30 (33%) patients normalized their tumor markers, while 20/30 (67%) had one or more persistently elevated markers. There was no difference in clinical or pathological stage between groups (P = 0.54 and P = 0.09, respectively). Further analysis showed a significantly lower rate and longer median time to recurrence/progression in the responder group (50% in responders vs. 90% in nonresponders at a median time of 22 vs. 4.8 months, respectively; P = 0.015). There was also significant difference in mortality rates and median overall survival between the study groups (30% in responders vs. 70% in nonresponders at a median time of 27.3 vs. 11.6 months respectively; P = 0.037). Two of the three patients that died in the normalized tumor marker group had tumor marker relapse at recurrence prior to their death.
CONCLUSIONS
To our knowledge, this is the first study showing tumor marker response to NAC. Patients with persistently elevated markers following NAC have a very poor prognosis following cystectomy, which may help identifying chemotherapy-resistant tumors. A larger, controlled study with longer follow up is needed to determine their role in predicting survival.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Female; Humans; Male; Middle Aged; Neoadjuvant Therapy; Prognosis; Prospective Studies; Treatment Outcome; Urinary Bladder Neoplasms
PubMed: 30470611
DOI: 10.1016/j.urolonc.2018.09.008 -
Molecular Cancer Research : MCR Aug 2019Insulinoma-associated-1 (IA-1 or INSM1) encodes a zinc-finger transcription factor, which was isolated from a human insulinoma subtraction library, with specific... (Review)
Review
Insulinoma-associated-1 (IA-1 or INSM1) encodes a zinc-finger transcription factor, which was isolated from a human insulinoma subtraction library, with specific expression patterns, predominantly in developing neuroendocrine tissues and tumors. INSM1 is key in early pancreatic endocrine, sympatho-adrenal lineage, and pan-neurogenic precursor development. gene ablation results in impairment of pancreatic β cells, catecholamine biosynthesis, and basal progenitor development during mammalian neocortex maturation. Recently, INSM1 has emerged as a superior, sensitive, and specific biomarker for neuroendocrine tumors. INSM1 regulates downstream target genes and exhibits extranuclear activities associated with multiple signaling pathways, including Sonic Hedgehog, PI3K/AKT, MEK/ERK, ADK, p53, Wnt, histone acetylation, LSD1, cyclin D1, Ascl1, and N-myc. Novel strategies targeting INSM1-associated signaling pathways facilitate the suppression of neuroendocrine tumor growth. In addition, INSM1 promoter-driven reporter assay and/or suicide gene therapy are promising effective therapeutic approaches for targeted specific neuroendocrine tumor therapy. In this review, the current knowledge of the biological role of INSM1 as a neuroendocrine tumor biomarker is summarized, and novel strategies targeting multiple signaling pathways in the context of INSM1 expression in neuroendocrine tumors are further explored. IMPLICATIONS: Neuroendocrine transcription factor (INSM1) may serve as a neuroendocrine biomarker for the development of novel cancer therapeutics against neuroendocrine tumors.
Topics: Antineoplastic Agents; Biomarkers, Tumor; Humans; Molecular Targeted Therapy; Neuroendocrine Tumors; Repressor Proteins; Signal Transduction
PubMed: 31113827
DOI: 10.1158/1541-7786.MCR-19-0286