Clinical Outcomes In Cancer Patients Research Articles

Whole-genome sequencing of chronic lymphocytic leukemia identifies subgroups with distinct biological and clinical features

The value of genome-wide over targeted driver analyses for predicting clinical outcomes of cancer patients is debated. Here, we report the whole-genome sequencing of 485 chronic lymphocytic leukemia patients enrolled in clinical trials as part of the United Kingdom’s 100,000 Genomes Project. We identify an extended catalog of recurrent coding and noncoding genetic mutations that represents a source for future studies and provide the most complete high-resolution map of structural variants, copy number changes and global genome features including telomere length, mutational signatures and genomic complexity. We demonstrate the relationship of these features with clinical outcome and show that integration of 186 distinct recurrent genomic alterations defines five genomic subgroups that associate with response to therapy, refining conventional outcome prediction. While requiring independent validation, our findings highlight the potential of whole-genome sequencing to inform future risk stratification in chronic lymphocytic leukemia.

NT157 exerts antineoplastic activity by targeting JNK and AXL signaling in lung cancer cells

Combination therapies or multi-targeted drugs have been pointed out as an option to prevent the emergence of resistant clones, which could make long-term treatment more effective and translate into better clinical outcomes for cancer patients. The NT157 compound is a synthetic tyrphostin that leads to long-term inhibition of IGF1R/IRS1-2-, STAT3- and AXL-mediated signaling pathways. Given the importance of these signaling pathways for the development and progression of lung cancer, this disease becomes an interesting model for generating preclinical evidence on the cellular and molecular mechanisms underlying the antineoplastic activity of NT157. In lung cancer cells, exposure to NT157 decreased, in a dose-dependent manner, cell viability, clonogenicity, cell cycle progression and migration, and induced apoptosis (p < 0.05). In the molecular scenario, NT157 reduced expression of IRS1 and AXL and phosphorylation of p38 MAPK, AKT, and 4EBP1. Besides, NT157 decreased expression of oncogenes BCL2, CCND1, MYB, and MYC and increased genes related to cellular stress and apoptosis, JUN, BBC3, CDKN1A, CDKN1B, FOS, and EGR1 (p < 0.05), favoring a tumor-suppressive cell signaling network in the context of lung cancer. Of note, JNK was identified as a key kinase for NT157-induced IRS1 and IRS2 phosphorylation, revealing a novel axis involved in the mechanism of action of the drug. NT157 also presented potentiating effects on EGFR inhibitors in lung cancer cells. In conclusion, our preclinical findings highlight NT157 as a putative prototype of a multitarget drug that may contribute to the antineoplastic arsenal against lung cancer.

Stress and cancer: The mechanisms of immune dysregulation and management.

Advances in the understanding of psychoneuroimmunology in the past decade have emphasized the notion that stress and cancer are interlinked closely. Durable chronic stress accelerated tumorigenesis and progression, which is unfavorable for clinical outcomes of cancer patients. Available evidence has provided unprecedented knowledge about the role and mechanisms of chronic stress in carcinogenesis, the most well-known one is dysfunction of the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS). With abnormal activation of neuroendocrine system, stress-related hormones contribute to increased oncogenes expression, exacerbated chronic inflammation and impaired immunologic function. In addition, accumulating studies have demonstrated that diverse stress interventions including pharmacological approaches, physical exercises and psychological relaxation have been administered to assist in mental disorders reduction and life quality improvement in cancer patients. In this review, we systematically summarize the connection and mechanisms in the stress-immune-cancer axis identified by animal and clinical studies, as well as conclude the effectiveness and deficiencies of existing stress management strategies.

Use of statins in cancer patients following acute myocardial infarction and its impact on long-term clinical outcomes

Abstract Background Statin use and its impact on long-term clinical outcomes in cancer patients following acute myocardial infarction (MI) remains insufficiently elucidated. Purpose We sought to analyze the prevalence of statins use in MI patients with cancer hospitalized in a tertiary cardio-oncology center and its influence on long-term mortality. Methods Of the 1,011 consecutive acute MI patients hospitalized between 2012 and 2017, cancer was found in 134 (13.3%) subjects including newly diagnosed cancer in 24 of them. All patients underwent coronary angiography. Within a median follow-up of 69.2 (37.8–79.9) months, a mortality rate, and its determinants were analyzed. Results Compared with non-cancer population, MI patients with cancer were older (73 [66–79] versus 68 [60–78] years, P&amp;lt;0.001), had lower hemoglobin level (12.8 [11.2–14.0] vs 13.8 [12.8–15.0], P&amp;lt;0.001), lower total cholesterol (4.1 [3.4–4.8] vs 4.4 [3.6–5.3], P=0.006) and lower HDL cholesterol (1.1 [0.9–1.4] vs 1.2 [1.0–1.6], P&amp;lt;0.001), without significant differences in LDL cholesterol (2.5 [1.9–3.1] vs 2.6 [1.7–3.4], P=0.70). Statins were prescribed less frequently in MI patients with cancer as compared with non-cancer MI population (80.5% versus 92.1%, P&amp;lt;0.001). Atorvastatin was the most frequent statin in both cancer and non-cancer groups (68.4% versus 75.1%, P=0.13). In cancer group simvastatin was more frequently (16.7% versus 5.9%, P&amp;lt;0.001) while rosuvastatin was less frequently (8.8% versus 18.9%, P=0.007) prescribed than in non-cancer patients. The independent determinants of no use of statins were anemia (hazard ratio [HR] 2.3, 95% confidence interval [95% CI] 1.3–4.2, P=0.006), no coronary artery stenosis &amp;gt;50% (HR 5.0, 95% CI 2.5–10.1, P&amp;lt;0.001) and cancer (HR 1.9, 95% CI 1.01–3.7, P=0.049) but not LDL cholesterol. The mortality rates were significantly higher in MI patients not treated with statins, both in non-cancer population (29.5%/year versus 6.7%/year, P&amp;lt;0.001) as well as in cancer group (53.9%/year versus 24.9%/year, P&amp;lt;0.05) as compared to those treated with statins (Figure 1). No statin use (HR 2.3, 95% CI 1.8–3.0, P&amp;lt;0.001), an active cancer (HR 2.3, 95% CI 1.8–3.0, P&amp;lt;0.001), patient's age (HR 2.3, 95% CI 1.8–2.9, P&amp;lt;0.001, per year) and anemia (HR 1.7, 95% CI 1.4–2.1, P&amp;lt;0.001) independently increased long-term mortality while no coronary artery stenosis &amp;gt;50% (HR 0.65, 95% CI 0.44–0.96, P=0.03) and better left ventricular ejection fraction (HR 0.97, 95% CI 0.96–0.98, P&amp;lt;0.001, per 1%) improved long-term survival. Conclusions An active cancer, anemia and lack of significant coronary lesions were associated with no use of statins in patients following MI. By multivariable approach both no statins use in MI patients independently on an active malignancy were associated with unfavorable long-term outcomes. Funding Acknowledgement Type of funding sources: None.

Modulation of the intestinal microbiota impacts the efficacy of immunotherapy in cancer patients - A recent literature survey.

In line with the current development of individualized cancer treatments, targeted and specialized therapeutic regimens such as immunotherapy gain importance and factors improving its efficacy come into the focus of actual research. Given the orchestrated interaction of the intestinal microbiota with host immunity the modulation of the human gut microbiota represents a therapy-enhancing factor. We therefore performed an actual literature survey on the role of the gut microbiota composition and the effects of its modification during immunotherapy of cancer patients. The included 23 studies published in the past 10 years revealed that both, distinct bacterial species and genera including Faecalibacterium prausnitzii and Bifidobacterium, respectively, enhanced distinct immunotherapy responses following PD-1/PD-L1 and CTLA-4 blockage, for instance, resulting in a better clinical outcome of cancer patients. Conversely, a high intestinal abundance of Bacteroidetes and Fusobacterium species correlated with a less efficient immunotherapy resulting in shorter progress-free survival outcomes. In conclusion, modifications of the gut microbiota by fecal microbiota transplantation or application of probiotic compounds represent potential adjunct options for immunotherapy in cancer patients which needs to be further addressed in future trials to provide individually tailored and safe adjuvant therapeutic measures in the combat of cancer.

Music Therapy as a Form of Nonpharmacologic Pain Modulation in Patients with Cancer: A Systematic Review of the Current Literature.

Simple SummaryCancer is a condition that affects millions of people worldwide each year. Treatments include pharmacologic and surgical interventions that can pose great risks to the physical and mental health of patients. The objective of this systematic review is to consolidate the literature surrounding the use of music therapy as a low-risk and effective pain management adjunct to traditional cancer therapy. This analysis reveals that the use of music therapy thus far has provided a nearly unanimous positive effect on cancer patients, with the potential to provide both physical and psychosocial benefits. The apparent adverse effects appear to be negligible, and music therapy should be considered when creating a cancer care plan.Aims and Objectives: To consolidate and summarize the current literature surrounding the use of music therapy as an effective noninvasive adjunct to conventional cancer therapy, especially as a low-risk alternative for pain management and anesthetic use in cancer patients. Background: Current studies have proposed that music therapy may be effective as a noninvasive adjunct to conventional cancer therapy in managing numerous outcomes in cancer patients. However, the findings of these investigations have not been consolidated and analyzed on a large scale. Therefore, focusing a systematic review on the effects of music therapy as an adjunct to conventional cancer therapy would give a better understanding of which intervention approaches are associated with better clinical outcomes for cancer patients. Design: A systematic review. Methods: A review of randomized controlled trials to evaluate the effectiveness of music therapy in physical, cognitive, and psychosocial outcomes for cancer patients alone or in conjunction with standard therapy was implemented. We conducted searches using the PubMed/MEDLINE, CINAHL, and Cochrane Library databases for all articles meeting the search criteria up until the time of article extraction in May, 2022. Only studies published in English were included. Two reviewers independently extracted data on participant and intervention characteristics. The main outcome variables included pain, anxiety, quality of life, mood, sleep disorders, fatigue, heart rate, blood pressure, respiratory rate, and oxygen saturation. Results: Of the 202 initially identified articles, 25 randomized controlled trials met the inclusion criteria for evaluation. Of the 25 studies, 23 (92.0%) reported statistically and clinically significant improvements across the outcome variables. Two of the studies (8.00%) found no significant positive effect from music therapy in any of the aforementioned outcomes variables. Conclusion: Music therapy, both as a standalone treatment and when used in conjunction with other pharmacologic and nonpharmacologic modalities, has a generally beneficial effect across several physiologic and psychosocial aspects of cancer.

From HDAC to Voltage-Gated Ion Channels: What's Next? The Long Road of Antiepileptic Drugs Repositioning in Cancer.

Simple SummaryAlthough in the last decades the clinical outcome of cancer patients considerably improved, the major drawbacks still associated with chemotherapy are the unwanted side effects and the development of drug resistance. Therefore, a continuous effort in trying to discover new tumor markers, possibly of diagnostic, prognostic and therapeutic value, is being made. This review is aimed at highlighting the anti-tumor activity that several antiepileptic drugs (AEDs) exert in breast, prostate and other types of cancers, mainly focusing on their ability to block the voltage-gated Na+ and Ca++ channels, as well as to inhibit the activity of histone deacetylases (HDACs), all well-documented tumor markers and/or molecular targets. The existence of additional AEDs molecular targets is highly suspected. Therefore, the repurposing of already available drugs as adjuvants in cancer treatment would have several advantages, such as reductions in dose-related toxicity CVs will be sent in a separate mail to the indicated address of combined treatments, lower production costs, and faster approval for clinical use.Cancer is a major health burden worldwide. Although the plethora of molecular targets identified in the last decades and the deriving developed treatments, which significantly improved patients’ outcome, the occurrence of resistance to therapies remains the major cause of relapse and mortality. Thus, efforts in identifying new markers to be exploited as molecular targets in cancer therapy are needed. This review will first give a glance on the diagnostic and therapeutic significance of histone deacetylase (HDAC) and voltage gated ion channels (VGICs) in cancer. Nevertheless, HDAC and VGICs have also been reported as molecular targets through which antiepileptic drugs (AEDs) seem to exert their anticancer activity. This should be claimed as a great advantage. Indeed, due to the slowness of drug approval procedures, the attempt to turn to off-label use of already approved medicines would be highly preferable. Therefore, an updated and accurate overview of both preclinical and clinical data of commonly prescribed AEDs (mainly valproic acid, lamotrigine, carbamazepine, phenytoin and gabapentin) in breast, prostate, brain and other cancers will follow. Finally, a glance at the emerging attempt to administer AEDs by means of opportunely designed drug delivery systems (DDSs), so to limit toxicity and improve bioavailability, is also given.

Effect of proton pump inhibitors on the clinical outcomes of PD-1/PD-L1 inhibitor in solid cancer patients.

Some concomitant drugs may affect the efficacy of programmed death protein-1/ ligand-1 (PD-1/L1) inhibitors. Among the various concomitant drugs, proton-pump inhibitors (PPI) have attracted some attention but have not reached a conclusion. We conducted a meta-analysis to evaluate the impact of PPIs on the survival of cancer patients treated with PD-1/L1 inhibitors. Related databases and conferences reports were searched. Studies that reported the relationship between PPI use and clinical outcomes of PD-1/L1 inhibitors were included. Meta-analysis was conducted to obtain pooled hazard ratios (HR)s with 95% confidence interval (CI). Eight studies involving 4869 cancer patients were included. Meta-analysis showed that PPI use was associated with worse overall survival (OS) (HR = 1.43, 95% CI 1.32-1.56), worse progression free survival (PFS) (HR = 1.30, 95% CI 1.20-1.40), and decreased objective response (odds ratio = 0.71, 95% CI 0.58-0.87) in cancer patients receiving PD-1/L1 inhibitors. Neither cancer type nor therapy type affected the effect of concomitant PPIs on the OS and PFS. In the subgroup of studies with a population size <500, PPIs did not reduce the OS, but the PFS. Only 1 single-center study was conducted, showing that PPI use did not affect the OS and PFS. There was no evidence of publication bias among included studies. Concomitant PPI use was correlated with worse clinical outcomes in cancer patients treated by PD-1/L1 inhibitors. Further prospective clinical and experimental studies are needed to confirm the effect and mechanism of PPI in worsening the clinical outcome of PD-1/L1 inhibitors.

Genome Editing Approaches with CRISPR/Cas9 for Cancer Treatment: Critical Appraisal of Preclinical and Clinical Utility, Challenges, and Future Research.

The increasing burden on human malignant diseases became a major concern for healthcare practitioners, that must deal with tumor relapse and the inability to efficiently treat metastasis, in addition to side effects. Throughout the decades, many therapeutic strategies have been employed to improve the clinical outcomes of cancer patients and great efforts have been made to develop more efficient and targeted medicines. The malignant cell is characterized by genetic and epigenetic modifications, therefore targeting those specific drivers of carcinogenesis is highly desirable. Among the genome editing technologies, CRISPR/Cas9 stood as a promising candidate for cancer treatment alternatives, due to its low complexity design. First described as a defense mechanism of bacteria against invading foreign DNA, later it was shown that CRISPR components can be engineered to target specific DNA sequences in a test tube, a discovery that was awarded later with the Nobel Prize in chemistry for its rapid expansion as a reliable genome editing tool in many fields of research, including medicine. The present paper aims of describing CRISPR/Cas9 potential targets for malignant disorders, and the approaches used for achieving this goal. Aside from preclinical studies, we also present the clinical trials that use CRISPR-based technology for therapeutic purposes of cancer. Finally, a summary of the presented studies adds a more focused view of the therapeutic value CRISPR/Cas9 holds and the associated shortcomings.

The Retrospective Study of Advanced Cancer Patients Receiving Integrative Cancer Treatments in single Comprehensive and Integrative Medicine Hospital

Objectives: Traditional Korean medicine (TKM) has been supplied as part of a national health care system in South Korea under a dual medical system, however it has been difficult to mix western medicine and TKM medical practices in existing hospitals. For the objective of innovative integration between them, Comprehensive and Integrative Medicine Hospital were founded in Daegu, South Korea. Here, we discussed the clinical outcomes of cancer patients who received integrative cancer treatment (ICT).Methods: A total of 678 patients previously diagnosed with cancer were retrospectively checked in our institution for 2 years. After applying inclusion/exclusion criteria, 573 patients were eligible for the final analysis. The overall survival (OS) of these patients in the aftercare period were determined. We looked at how clinical factors and treatments including chemotherapy, complementary and alternative medicine (CAM), and TKM affected the OS.Results: At the first visit, 212 subjects had no evidence of disease after tumor resection and 355 ones with advanced cancer, who receiving ICT including chemotherapy, CAM, and TKM showed better OS compared to the CAM including TKM or the best supportive care (median OS = 216, 78, and 46 days, respectively). The median OS was not reached in TKM only, even though the sample size was small (N = 12). Even after adjusting for clinical factors associated to liver, renal, and hematologic manifestation, ICT still remained significant.Conclusions: We demonstrated that ICT might be beneficial for advanced cancer regardless of the performance status, liver and renal function, since it positively affected the OS.

EP16.02-017 Predictive Value of Peripheral Blood Immune Cell Profiling in EGFR-T790M Mutant Lung Adenocarcinoma

Peripheral immune cell profiles have been shown to correlate with clinical outcomes in cancer patients. Exploring the peripheral blood immune cell profile of lung adenocarcinoma (LUAD) patients will likely be a biomarker for predicting the efficacy of osimertinib.

Prognostic and clinicopathologic significance of circZFR in multiple human cancers

BackgroundAbnormally expressed in diverse cancers, circZFR has been correlated with clinical outcomes of cancer patients. Aim of this meta-analysis was to elucidate the prognostic role of circZFR in multiple human malignancies.MethodsLiterature retrieval was conducted by systematically searching on Pubmed, Web of Science, and the Cochrane Library up to December 2nd, 2021. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were pooled to evaluate the association between circZFR expression and overall survival (OS). The reliability of the pooled results was assessed through sensitivity analysis and the publication bias was measured by Begg’s and Egger’s test.ResultsA total of seventeen studies comprising 1098 Chinese patients were enrolled in this meta-analysis. Results demonstrated that high circZFR expression was correlated with an unfavorable OS (HR = 2.14, 95% CI 1.74, 2.64). High circZFR expression predicted larger tumor size (OR = 2.79, 95% CI 1.52, 5.12), advanced clinical stage (OR = 3.38, 95% CI 1.49, 7.65), tendentiousness of lymph node metastasis (LNM) (OR = 3.08, 95% CI 2.01, 4.71), and malignant grade (OR = 3.18, 95% CI 1.09, 9.30), but not related to age, gender, and distant metastasis (DM).ConclusionsHigh circZFR expression was associated with unfavorable OS and clinicopathologic parameters including tumor size, clinical stage, LNM, and histology grade, implicating a promising prognostic factor in cancers.

Percutaneous Coronary Angioplasty in Patients with Cancer: Clinical Challenges and Management Strategies.

The number of cancer survivors in the United States is projected to increase by 31% by 2030. With advances in early screening, diagnosis and therapeutic strategies, a steadily increasing number of patients are surviving cancer. Coronary artery disease (CAD) is now one of the leading causes of death amongst cancer survivors, with the latter group of patients having a higher risk of CAD compared to the general population. Our review covers a range of specific challenges faced by doctors when considering percutaneous coronary interventions (PCI) in cancer patients; clinical outcomes in cancer patients undergoing PCI, as well as some important technical considerations to be made when making decisions regarding the management strategy in this special population of patients.

Role of MicroRNA-7 (MiR-7) in Cancer Physiopathology.

miRNAs are non-coding RNA sequences of approximately 22 nucleotides that interact with genes by inhibiting their translation through binding to their 3′ or 5′ UTR regions. Following their discovery, the role they play in the development of various pathologies, particularly cancer, has been studied. In this context, miR-7 is described as an important factor in the development of cancer because of its role as a tumor suppressor, regulating a large number of genes involved in the development and progression of cancer. Recent data support the function of miR-7 as a prognostic biomarker in cancer, and miR-7 has been proposed as a strategy in cancer therapy. In this work, the role of miR-7 in various types of cancer is reviewed, illustrating its regulation, direct targets, and effects, as well as its possible relationship to the clinical outcome of cancer patients.

Methylation of HBP1 by PRMT1 promotes tumor progression by regulating actin cytoskeleton remodeling

HBP1 is a sequence-specific transcription factor which generally considered as a crucial growth inhibitor. Posttranslational modification of HBP1 is vital for its function. In this study, we demonstrate that HBP1 is methylated at R378 by PRMT1, which decreases HBP1 protein stability by promoting its ubiquitination and proteasome-mediated degradation. PRMT1-mediated methylation of HBP1 alleviates the repressive effects of HBP1 on tumor metastasis and growth. GSN is identified as a novel target gene of HBP1. Methylation of HBP1 promotes actin cytoskeleton remodeling, glycolysis and tumor progression by downregulating GSN (a vital actin-binding protein) levels. The methylated HBP1-GSN axis is associated with the clinical outcomes of cancer patients. This investigation elucidates the mechanism of how methylated HBP1 facilitates actin cytoskeleton remodeling, thus attenuates its tumor-suppressive function and promotes tumor progression. Targeting methylated HBP1-GSN axis may provide a therapeutic strategy for cancer.

The Effect of the Gut Microbiota on Systemic and Anti-Tumor Immunity and Response to Systemic Therapy against Cancer.

Simple SummaryThe gut microbiome affects the development of systemic immune response and it can also impact response to systemic treatments such as immunotherapy and chemotherapy. This article provides and in-depth overview of various mechanisms that the gut microbiome interacts with the immune system, cancer, and how it affects anti-tumor immunity and response to immunotherapy.Gut microbiota can have opposing functions from pro-tumorigenic to anti-tumorigenic effects. Increasing preclinical and clinical evidence suggests that the intestinal microbiota affects cancer patients’ response to immune checkpoint inhibitors (ICIs) immunotherapy, such as anti-programmed cell death protein 1 (PD-1) and its ligand (PD-L1) and anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4). Microbiota-induced inflammation possibly contributes to tumor growth and cancer development. Microbiota-derived metabolites can also be converted to carcinogenic agents related to genetic mutations and DNA damage in organs such as the colon. However, other attributes of microbiota, such as greater diversity and specific bacterial species and their metabolites, are linked to better clinical outcomes and potentially improved anti-tumor immunity. In addition, the intratumoral microbial composition strongly affects T-cell-mediated cytotoxicity and anti-tumor immune surveillance, adding more complexity to the cancer-microbiome-immune axis. Despite the emerging clinical evidence for the activity of the gut microbiota in immuno-oncology, the fundamental mechanisms of such activity are not well understood. This review provides an overview of underlying mechanisms by which the gut microbiota and its metabolites enhance or suppress anti-tumor immune responses. Understanding such mechanisms allows for better design of microbiome-specific treatment strategies to improve the clinical outcome in cancer patients undergoing systemic therapy.

LB928 Distinguishing morphologic characteristics of cutaneous immune-related adverse events among patients receiving immune checkpoint inhibitors combined with other anti-cancer therapies

Novel combination regimens with immune-checkpoint inhibitors (ICIs) and targeted agents, chemotherapy, and non-ICI immunotherapies have led to unprecedented clinical outcomes in cancer patients, though there is little research describing the morphological patterns of cutaneous toxicities resulting from such regimens. We sought to characterize the clinical morphology of cutaneous immune-related adverse events (cirAEs) caused by ICIs alongside other anti-cancer therapy compared to ICI monotherapy. In this multi-institutional retrospective cohort study, we identified patients receiving ICI therapy at MGH (n=628; 1/1/16-6/29/21) and VUMC (n=6; 7/1/17-1/1/22) who developed cirAEs. Patients were categorized by regimen into those receiving ICI monotherapy (ICI-only) or ICI alongside other targeted agents, chemotherapy, or non-ICI immunotherapy (ICI-plus). Multivariate logistic regression was used to assess differences in cirAE characteristics based on ICI-only vs. ICI-plus status. Among 634 cirAE patients, 96 were ICI-plus and 538 were ICI-only. ICI-plus patients had a lower odds of developing isolated pruritus compared to ICI-only cases (OR: 0.19, 95% CI: 0.07-0.54, p=0.002). ICI-plus cirAEs were more likely to present as maculopapular (OR: 2.19, 95% CI: 1.26-3.80; p=0.005) and morbilliform (OR: 5.23, 95% CI: 1.34-20.37, p=0.017) eruptions compared to ICI-only. cirAEs were commonly described as having a single morphology regardless of ICI-plus status, suggesting that the concurrent use of ICIs and other anti-cancer therapies leads to synergistic cutaneous toxicities presenting with singular primary morphologies. Further research into how morphologic subtypes of cirAEs manifest in the setting of combination therapy will allow for the earlier recognition and improved management of cutaneous toxicities.

Clinicopathological Significance and Prognostic Values of Long Noncoding RNA BCYRN1 in Cancer Patients: A Meta-Analysis and Bioinformatics Analysis.

Background Although combination therapies have substantially improved the clinical outcomes of cancer patients, the prognosis and early diagnosis remain unsatisfactory. As a result, it is critical to look for novel indicators linked to cancer. Despite a number of recent studies indicating that the lncRNA brain cytoplasmic RNA1(BCYRN1) may be a potential predictive biomarker in cancer patients, BCYRN1's prognostic value is still being debated. Methods We utilized PubMed, Embase, Web of Science, and the Cochrane Library to search for studies related to BCYRN1 until October 2021. Valid data were extracted after determining the articles according to the inclusion and exclusion criteria, and forest plots were made using Stata software. We used hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals to evaluate the relationship between abnormal BCYRN1 expression and patient prognosis and clinicopathological characteristics. Results Meta-analysis revealed that increased BCYRN1 expression was associated with both overall tumor survival (OS; HR = 1.84, 95% CI 1.51–2.25, p < 0.0001) and disease-free survival (DFS; HR = 1.65, 95% CI 1.20–2.26, p=0.002). Furthermore, a strong association was discovered between increased BCYRN1 expression and tumor invasion depth (OR = 2.11, 95% CI 1.49–2.99, p=0.000), clinical stage (OR = 2.52, 95% CI 1.18–5.37, p=0.017), and distant tumor metastasis (OR = 4.19, 95% CI 1.45–12.05, p=0.008). Conclusions We found that high BCYRN1 expression was associated with poor survival prognosis and aggressive clinicopathological characteristics in various cancers, indicating that it is a potential prognostic indicator as well as a therapeutic target. Further research is needed on pan-cancer cohorts to determine the clinical relevance of BCYRN1 in distinct cancer types.

A pipeline for copy number profiling of single circulating tumour cells to assess intrapatient tumour heterogeneity.

Intrapatient tumour heterogeneity is likely a major determinant of clinical outcome in cancer patients. To assess heterogeneity in a minimally invasive manner, methods to perform single circulating tumour cell (CTC) genomics at high resolution are necessary. However, due to the rarity of CTCs, development of such methods is challenging. Here, we developed a modular single CTC analysis pipeline to assess intrapatient heterogeneity by copy number (CN) profiling. To optimize this pipeline, spike‐in experiments using MCF‐7 breast cancer cells were performed. The VyCAP puncher system was used to isolate single cells. The quality of whole genome amplification (WGA) products generated by REPLI‐g and Ampli1™ methods, as well as the results from the Illumina Truseq and the Ampli1™ LowPass library preparation techniques, was compared. Moreover, a bioinformatic pipeline was designed to generate CN profiles from single CTCs. The optimal combination of Ampli1™ WGA and Illumina Truseq library preparation was successfully validated on patient‐derived CTCs. In conclusion, we developed a novel modular pipeline to isolate single CTCs and subsequently generate detailed patient‐derived CN profiles that allow assessment of intrapatient heterogeneity in future studies.

Applications of artificial intelligence multiomics in precision oncology.

Cancer is the second leading worldwide disease that depends on oncogenic mutations and non-mutated genes for survival. Recent advancements in next-generation sequencing (NGS) have transformed the health care sector with big data and machine learning (ML) approaches. NGS data are able to detect the abnormalities and mutations in the oncogenes. These multi-omics analyses are used for risk prediction, early diagnosis, accurate prognosis, and identification of biomarkers in cancer patients. The availability of these cancer data and their analysis may provide insights into the biology of the disease, which can be used for the personalized treatment of cancer patients. Bioinformatics tools are delivering this promise by managing, integrating, and analyzing these complex datasets. The clinical outcomes of cancer patients are improved by the use of various innovative methods implicated particularly for diagnosis and therapeutics. ML-based artificial intelligence (AI) applications are solving these issues to a great extent. AI techniques are used to update the patients on a personalized basis about their treatment procedures, progress, recovery, therapies used, dietary changes in lifestyles patterns along with the survival summary of previously recovered cancer patients. In this way, the patients are becoming more aware of their diseases and the entire clinical treatment procedures. Though the technology has its own advantages and disadvantages, we hope that the day is not so far when AI techniques will provide personalized treatment to cancer patients tailored to their needs in much quicker ways.