Common Form Of Cancer Research Articles

EE508 Cost of Liver Cancer Screening in Patients with Cirrhosis

Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, is the fastest growing cause of cancer deaths among Americans. Guidelines recommend biannual ultrasound-based screening, with or without a serum biomarker alpha fetoprotein (AFP) for early detection of HCC in at-risk individuals with cirrhosis. Our objective was to estimate the overall cost of HCC screening from a commercial healthcare system’s perspective.

Barriers in the identification and diagnosis of hereditary colon cancer.

e13524 Background: Lynch Syndrome (LS), the most common form of hereditary colorectal cancer (CRC), is due to germline pathogenic variant (PV) in mismatch repair genes (MMR). Since 2009, the National Comprehensive Cancer Network (NCCN) recommends MMR screening for LS for all CRCs regardless of age. The American College of Medical Genetics and Genomics recommends patients with MMR deficiency or microsatellite instability (MSI) be referred for genetic testing. Despite these recommendations, compliance is low. The aim of this study was to evaluate compliance with LS screening and genetic testing in CRC. Methods: A single institution retrospective review of patients diagnosed with CRC from 2018-2021 was performed. A chart review of those diagnosed in 2018 and 2021 was analyzed and combined as a single population from pre and post COVID periods. A student’s T-Test was used to compare continuous variables and chi square for categorical variables within the two populations. The compliance with either MSI or MMR screening was calculated. Meeting criteria for genetic testing was defined as age less than 50, MSI-L/H or MMR deficient. These patients were then analyzed to determine the proportion of genetic referrals, genetic counseling, genetic testing and identification of LS. Results: 276 patients with CRC were reviewed, 153 in 2018, 123 in 2021. 71.2% were Caucasian and 58% male. There was no statistically significant difference in gender, race or ethnicity, however, there was a difference in age, with a younger average age in 2021 (67, 63; p = 0.014). 146 (53%) patients were screened for LS. 44 (16%) with MSI, 19 (7%) MMR and 82 (30%) with both. 78 patients met criteria for genetic testing; 47 due to age alone, 6 age and positive LS screening and 25 screening alone. 35% (27/78) of those meeting criteria were referred to genetics, of which 63% (17/27) completed their appointment, 63% (17/27) were tested, and 37% (10/27) had a PV identified. Conclusions: Despite guidelines for LS screening, compliance is low with only half of CRC patients appropriately screened at our institution. Even patients with positive screening and those less than 50 were not referred for genetic testing. However, of referred patients, 63% completed their appointment and all those were tested. This supports the idea that poor compliance with genetic testing is not due to patient compliance, but shows a systems issue at a higher level. To improve LS identification, reflex screening and genetic referrals are paramount. In our study, 59% of patients with germline testing had a PV, however 65% of those meeting criteria were never referred, which could reflect a proportion of patients with LS going unidentified. This validates the 2022 NCCN guidelines recommending genetic testing for all CRCs despite age or MSI/MMR status. By removing the barrier of MMR testing, more genetic testing will likely be done. [Table: see text]

Application and Performance of Artificial Intelligence (AI) in Oral Cancer Diagnosis and Prediction Using Histopathological Images: A Systematic Review.

Oral cancer (OC) is one of the most common forms of head and neck cancer and continues to have the lowest survival rates worldwide, even with advancements in research and therapy. The prognosis of OC has not significantly improved in recent years, presenting a persistent challenge in the biomedical field. In the field of oncology, artificial intelligence (AI) has seen rapid development, with notable successes being reported in recent times. This systematic review aimed to critically appraise the available evidence regarding the utilization of AI in the diagnosis, classification, and prediction of oral cancer (OC) using histopathological images. An electronic search of several databases, including PubMed, Scopus, Embase, the Cochrane Library, Web of Science, Google Scholar, and the Saudi Digital Library, was conducted for articles published between January 2000 and January 2023. Nineteen articles that met the inclusion criteria were then subjected to critical analysis utilizing QUADAS-2, and the certainty of the evidence was assessed using the GRADE approach. AI models have been widely applied in diagnosing oral cancer, differentiating normal and malignant regions, predicting the survival of OC patients, and grading OC. The AI models used in these studies displayed an accuracy in a range from 89.47% to 100%, sensitivity from 97.76% to 99.26%, and specificity ranging from 92% to 99.42%. The models' abilities to diagnose, classify, and predict the occurrence of OC outperform existing clinical approaches. This demonstrates the potential for AI to deliver a superior level of precision and accuracy, helping pathologists significantly improve their diagnostic outcomes and reduce the probability of errors. Considering these advantages, regulatory bodies and policymakers should expedite the process of approval and marketing of these products for application in clinical scenarios.

CemiplimAb-rwlc survivorship and epidemiology (CASE): A prospective study of safety and efficacy of cemiplimab in patients with advanced basal cell carcinoma in a real-world setting.

TPS9614 Background: Basal cell carcinoma (BCC) is the most common form of non-melanoma skin cancer in the United States. Surgical excision is the standard treatment, with < 1% of cases progressing to locally advanced or metastatic disease. Hedgehog pathway inhibitors (HHIs) are the first-line therapy for advanced BCC (aBCC); the US Food and Drug Administration and European Medicines Agency have approved the use of cemiplimab (a programmed cell death-1 inhibitor) in advanced BCC (aBCC) patients previously treated with (or are inappropriate for) HHI. Limited real-world data exist on the clinical characteristics, disease management and progression, and survivorship of patients with aBCC. The ongoing C.A.S.E. study aims to evaluate the efficacy, safety, disease evolution, survivorship, and patient reported outcomes (PRO) in patients treated with cemiplimab in the real-world setting. Methods: This trial in progress (NCT03836105) aims to describe the effectiveness and safety of cemiplimab 350 mg administered every 3 weeks for treatment of patients with aBCC in real-world clinical settings. Up to 100 adult patients with aBCC who are prescribed commercially available cemiplimab from ~65 study sites in the United States will be included. The duration of follow-up will be 24 months. Endpoints for this study relate to real-world efficacy, including overall survival; progression-free survival; objective response rate, (partial or complete response); and disease control rate, defined as the percentage who do not progress for ≥ 6 months; Time to response, duration of response, time to treatment failure, and disease-specific death will also be assessed. Real-world safety outcomes will also be captured, including immune-related adverse events, infusion-related reactions, and serious adverse events. Patient selection criteria and treatment patterns will be analyzed using descriptive statistics. This study also aims to describe the patient experience of real-world treatment with cemiplimab. PROs including global quality of life, functioning, and symptoms will be captured at baseline and follow-up visits via the EORTC QLQ-C30 and the Skin Care Index. Recruitment for this trial is ongoing. Clinical trial information: NCT03836105 .

History of Mammography: Analysis of Breast Imaging Diagnostic Achievements over the Last Century.

Breast cancer is the most common forms of cancer and a leading cause of mortality in women. Early and correct diagnosis is, therefore, essential to save lives. The development of diagnostic imaging applied to the breast has been impressive in recent years and the most used diagnostic test in the world is mammography, a low-dose X-ray technique used for imaging the breast. In the first half of the 20th century, the diagnosis was in practice only clinical, with consequent diagnostic delay and an unfavorable prognosis in the short term. The rise of organized mammography screening has led to a remarkable reduction in mortality through the early detection of breast malignancies. This historical review aims to offer a complete panorama of the development of mammography and breast imaging during the last century. Through this study, we want to understand the foundations of the pillar of radiology applied to the breast through to the most modern applications such as contrast-enhanced mammography (CEM), artificial intelligence, and radiomics. Understanding the history of the development of diagnostic imaging applied to the breast can help us understand how to better direct our efforts toward an increasingly personalized and effective diagnostic approach. The ultimate goal of imaging applied to the detection of breast malignancies should be to reduce mortality from this type of disease as much as possible. With this paper, we want to provide detailed documentation of the main steps in the evolution of breast imaging for the diagnosis of breast neoplasms; we also want to open up new scenarios where the possible current and future applications of imaging are aimed at being more precise and personalized.

TMEM33 as a Prognostic Biomarker of Cervical Cancer and Its Correlation with Immune Infiltration.

In women all over the world, cervical cancer (CC) ranks as the fourth most common form of cancer to be diagnosed. It was previously reported that transmembrane protein 33(TMEM33) could report a poor prognosis in several cancers. The current study is aimed at investigating the potential prognostic value of TMEM33 and its relevance to the tumor microenvironment in CC in a comprehensive manner. In this study, CC specimens presented noticeably higher TMEM33 expression level in comparison to nontumor specimens. In pan-cancer assays, it was found that TMEM33 was present at a high level in many different kinds of tumors. We found that patients with CC patients who had a high TMEM33 expression presented worse overall survival (OS) and disease-free survival (DFS) relative to patients who had a low TMEM33 expression. According to the results of a multivariate analysis, a high level of TMEM33 expression can significantly and independently predict the prognosis of CC. The levels of TMEM33 were found to have a negative correlation with resting dendritic cells, resting mast cells, plasma cells, T cells CD8, T cells regulatory, and regulatory T cells. Finally, we confirmed that TMEM33 was overexpressed in CC cells, and its knockdown distinctly suppressed the proliferation and invasion of CC cells. Overall, we provided evidences that TMEM33 could be used as a potential biomarker to assess the prognosis and the level of immune infiltration in CC.

Childhood Leukemia: A Review

Leukemia is cancer of the blood. It’s the most common form of cancer in childhood. The cancer cells grow in bone marrow and go into the blood. The bone marrow is the soft, spongy centre of some bones. It makes blood cells. When a child has leukemia, the bone marrow makes abnormal blood cells that don’t mature. The abnormal cells are usually white blood cells (leukocytes). The bone marrow also makes fewer healthy cells. The abnormal cells reproduce very quickly. Children with leukaemia can need treatment for up to 3 years.

The international scandal of defective asparaginase: A blight on children with cancer.

Acute lymphoblastic leukemia is the commonest form of cancer in children and adolescents worldwide, and asparaginase is an essential component of successful chemotherapy for this disease associated with long-term survival rates often exceeding 90% in high-income countries. Demonstrably defective preparations of asparaginase, distributed from China and India, increase the burden of morbidity and mortality, reducing attainable survival rates. This adverse outcome is enabled by inadequate regulation and oversight, especially in resource-poor settings in low- and middle-income countries where the great majority of children and adolescents with cancer live. The pediatric oncology community must rise to the challenge.

Recent Mortality Patterns and Time Trends for the Major Cancers in 47 Countries Worldwide.

Most prior studies have reported cancer mortality trends across countries for specific cancer types. Herein, we examine recent patterns and trends in cancer mortality rates for the eight common forms of cancer in 47 countries across five continents (except Africa) based on the World Health Organization mortality database. Rates were age-standardized to the 1966 Segi-Doll world population, and trends in the age-standardized rates for the most recent 10 years of data were examined using Joinpoint regression. Cancer-specific mortality rates vary substantially across countries, with rates of infection-related (cervix and stomach) and tobacco-related cancers (lung and esophagus) varying by 10-fold. Recent mortality rates for all major cancers decreased in most of the studied countries except lung cancer in females and liver cancer in males, where increasing rates were observed in most countries. Rates decreased or stabilized in all countries for lung cancer in men and stomach cancer in both sexes. The findings reinforce the importance of implementing and strengthening resource-stratified and targeted cancer prevention and control programs in all parts of the world to further reduce or halt the rising cancer burden. The results may inform cancer prevention and treatment strategies and in so doing, reduce the marked global cancer disparities observed today.

Integrated analysis of single-cell chromatin state and transcriptome identified common vulnerability despite glioblastoma heterogeneity

In 2021, the World Health Organization reclassified glioblastoma, the most common form of adult brain cancer, into isocitrate dehydrogenase (IDH)-wild-type glioblastomas and grade IV IDH mutant (G4 IDHm) astrocytomas. For both tumor types, intratumoral heterogeneity is a key contributor to therapeutic failure. To better define this heterogeneity, genome-wide chromatin accessibility and transcription profiles of clinical samples of glioblastomas and G4 IDHm astrocytomas were analyzed at single-cell resolution. These profiles afforded resolution of intratumoral genetic heterogeneity, including delineation of cell-to-cell variations in distinct cell states, focal gene amplifications, as well as extrachromosomal circular DNAs. Despite differences in IDH mutation status and significant intratumoral heterogeneity, the profiled tumor cells shared a common chromatin structure defined by open regions enriched for nuclear factor 1 transcription factors (NFIA and NFIB). Silencing of NFIA or NFIB suppressed invitro and invivo growths of patient-derived glioblastomas and G4 IDHm astrocytoma models. These findings suggest that despite distinct genotypes and cell states, glioblastoma/G4 astrocytoma cells share dependency on core transcriptional programs, yielding an attractive platform for addressing therapeutic challenges associated with intratumoral heterogeneity.

Clinical and Translational Applications of Serological and Histopathological Biomarkers in Metastatic Breast Cancer: A Comprehensive Review.

Breast cancer is one of the most common malignancies worldwide and the most common form of cancer in women. A large proportion of patients begin with localized disease and undergo treatment with curative intent, while another large proportion of patients debuts with disseminated metastatic disease. In the last subgroup of patients, the prognosis in recent years has changed radically, given the existence of different targeted therapies thanks to the discovery of different biomarkers. Serological, histological, and genetic biomarkers have demonstrated their usefulness in the initial diagnosis, in the follow-up to detect relapses, to guide targeted treatment, and to stratify the prognosis of the most aggressive tumors in those with breast cancer. Molecular markers are currently the basis for the diagnosis of metastatic disease, given the wide variety of chemotherapy regions and existing therapies. These markers have been a real revolution in the therapeutic arsenal for breast cancer, and their diagnostic validity allows the classification of tumors with higher rates of relapse, aggressiveness, and mortality. In this sense, the existence of therapies targeting different molecular alterations causes a series of changes in tumor biology that can be assessed throughout the course of the disease to provide information on the underlying pathophysiology of metastatic disease, which allows us to broaden our knowledge of the different mechanisms of tissue invasion. Therefore, the aim of the present article is to review the clinical, diagnostic, predictive, prognostic utility and limitations of the main biomarkers available and under development in metastatic breast cancer.

Retinoic acid receptor β modulates mechanosensing and invasion in pancreatic cancer cells via myosin light chain 2

Pancreatic ductal adenocarcinoma (PDAC) is the most common and lethal form of pancreatic cancer, characterised by stromal remodelling, elevated matrix stiffness and high metastatic rate. Retinoids, compounds derived from vitamin A, have a history of clinical use in cancer for their anti-proliferative and differentiation effects, and more recently have been explored as anti-stromal therapies in PDAC for their ability to induce mechanical quiescence in cancer associated fibroblasts. Here, we demonstrate that retinoic acid receptor β (RAR-β) transcriptionally represses myosin light chain 2 (MLC-2) expression in pancreatic cancer cells. As a key regulatory component of the contractile actomyosin machinery, MLC-2 downregulation results in decreased cytoskeletal stiffness and traction force generation, impaired response to mechanical stimuli via mechanosensing and reduced ability to invade through the basement membrane. This work highlights the potential of retinoids to target the mechanical drivers of pancreatic cancer.

Abstract #1406506: Hidden in Plain Sight: Incidental Diagnosis of Metastatic Papillary Thyroid Microcarcinoma without Radiologically-Apparent Thyroid Tumor

Papillary thyroid cancer (PTC) is considered the most common form of thyroid cancer. Papillary thyroid microcarcinomas (PTMC) are defined as papillary carcinomas that are <1 cm and are often identified on surgical pathology but may be missed by ultrasound imaging. We present the case of a 24-year-old woman who initially presented with a right lateral neck lump. This had been noted for 3-4 years and she had been told this was likely a lipoma. Therefore, no workup was done until it began to grow during pregnancy. Following pregnancy, she underwent excision with findings of a level 5B lymph node 2.1 x 2.1 x 0.9 cm with pathology consisting of PTC, follicular variant. Neck ultrasound done in an imaging center and in our clinic did not reveal thyroid nodules or abnormal appearing lymph nodes. She was referred for total thyroidectomy with central neck and limited right neck dissection. Surgical pathology showed right superior lobe 0.5 cm PTMC, follicular variant with negative surgical margins. Seven out of twenty-four lymph nodes were positive in the right central compartment and in levels 3 and 4. The largest metastatic lesion measured 0.9 cm. Solid tumor profiling assay identified a NTRK3 fusion: ETV6(4)-NTRK3(14) mutation. She did well following surgery and had RAI ablation following thyroid hormone withdrawal. Follow up ultrasound 1 year later showed no signs of structural recurrence and thyroglobulin levels have remained undetectable. She is currently on 150 mcg of levothyroxine and doing well clinically. PTMC are identified with increased frequency due to improved ultrasound imaging and FNA techniques and may represent over 40% of PTC. PTMC are generally considered to carry a favorable prognosis. However, cervical lymph node metastasis is reported in 10-17% of patients with PTMC undergoing total thyroidectomy. There has been growing interest in NTRK fusion mutations in PTC. NTRK mutations have been previously described with higher frequency in pediatric populations but are increasingly recognized in adult cohorts. NTRK fusion mutations are identified in up to 13% of PTMC and some studies suggest higher risk of metastasis. This case is unusual in that nodal metastasis were present even without a sizable primary thyroid tumor. Although more studies are needed to elucidate the clinical and prognostic significance of NTRK fusion mutations in PTMC, their response to TRK inhibitors may represent a future pathway for treatment.

Abstract IA19: Oncogenic KRAS and the regulation of the pancreatic cancer microenvironment.

Abstract Pancreatic ductal adenocarcinoma, the most common form of pancreatic cancer, is characterized by almost universal presence of oncogenic KRAS. A key characteristic of pancreatic cancer is the abundant accumulation of tumor microenvironment, rich in infiltrating immune cells and an extensive fibroblast population. Pancreatic cancer is preceded by precursor lesions known as Pancreatic Intraepithelial Neoplasia (PanIN); PanIN formation is accompanied by the formation of a pre-TME. Analysis of donor pancreas from healthy individual revealed that PanIN is common in human samples, and accompanied by pre-TME accumulation in human samples. We sought to determine whether oncogenic KRAS drives accumulation and maintenance of the pre-TME. For this purpose, we utilized the iKRAS mouse model of pancreatic cancer, which allows tissue-specific, inducible and reversible activation of KRASG12D, the most common mutant form in human pancreatic cancer. Activation of oncogenic KRAS in iKRAS mice leads to PanIN formation. We observed that fibroblast activation occurs upon KRAS activation and precedes the formation of overt lesions. Further, epithelial oncogenic KRAS is required to maintain fibroblast reprogramming in PanIN. To comprehensively understand changes in fibroblasts, we used single cell RNA sequencing, and observed that the fibroblast transcriptional program is extrinsically regulated by epithelial oncogenic KRAS. The reprogramming process can be modeled in vivo using conditioned media from pancreatic cancer cells expressing oncogenic KRAS, and is mediated by JAK/STAT3 signaling in fibroblasts. We then sought to determine whether the extrinsic effects of oncogenic KRAS induced reprogramming of fibroblasts at distal sites. We chose to study the lung, which is a common site of metastasis for pancreatic cancer. Our data show that lung fibroblasts are activated following expression of oncogenic KRAS in the pancreas; fibroblast activation is accompanied by phospho-Stat3 signaling, a readout of the JAK/Stat3 pathway, and precedes metastasis outgrowth in the pancreas. Thus, oncogenic KRAS extrinsically reprograms the local and systemic environments, possibly facilitating metastatic spread of pancreatic cancer. Citation Format: Marina Pasca di Magliano. Oncogenic KRAS and the regulation of the pancreatic cancer microenvironment. [abstract]. In: Proceedings of the AACR Special Conference: Targeting RAS; 2023 Mar 5-8; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Res 2023;21(5_Suppl):Abstract nr IA19.

Radiotherapy Role in Rectal Cancer at Prof. Dr. R. D. Kandou General Hospital, Manado, Indonesia

Abstract: Rectal cancer (RC) remains as a major health burden, being the 3rd most common form of cancer and leading cause of death. RC effects as much as 12.8 per 100 adult population with a mortality rate as high as 9.5%.1 Efforts were made to reduce morbidity and mortality due to rectal cancer. One of them is radiotherapy acting as both neoadjuvant and adjuvant. Thus study aimed to emphasize the role of radioteraphy in treating rectal cancer patients at Prof. Dr. R. D. Kandou General Hospital, Manado. This was a retrospective study using data of all rectal cancer outpatients seeking at Prof. Dr. R. D. Kandou General Hospital, Manado. from 2017-2020 especially of those receiving radiotherapy treatment in radiology department. The results obtained a total 119 patients, 28 of them received radiotherapy based on staging and clinical judgement. From the radiotherapy group, 46.4% patient received neoadjuvant radiotherapy primary to surgical procedure, and among the neoadjuvant group 71.4% received long course radiotherapy. From the neoadjuvant radiotherapy group, 46.4% became resectable and 46.4% among them underwent Miles Procedure. In conclusion, rectal cancer is still a health problem, and radiotherapy as one of the modality play major role as neoadjuvant and adjuvant treatment.

The Emergence of TRP Channels Interactome as a Potential Therapeutic Target in Pancreatic Ductal Adenocarcinoma

Integral membrane proteins, known as Transient Receptor Potential (TRP) channels, are cellular sensors for various physical and chemical stimuli in the nervous system, respiratory airways, colon, pancreas, bladder, skin, cardiovascular system, and eyes. TRP channels with nine subfamilies are classified by sequence similarity, resulting in this superfamily's tremendous physiological functional diversity. Pancreatic Ductal Adenocarcinoma (PDAC) is the most common and aggressive form of pancreatic cancer. Moreover, the development of effective treatment methods for pancreatic cancer has been hindered by the lack of understanding of the pathogenesis, partly due to the difficulty in studying human tissue samples. However, scientific research on this topic has witnessed steady development in the past few years in understanding the molecular mechanisms that underlie TRP channel disturbance. This brief review summarizes current knowledge of the molecular role of TRP channels in the development and progression of pancreatic ductal carcinoma to identify potential therapeutic interventions.

HILPDA promotes NASH-driven HCC development by restraining intracellular fatty acid flux in hypoxia

The prevalence of non-alcoholic steatohepatitis (NASH)-driven hepatocellular carcinoma (HCC) is rising rapidly, yet its underlying mechanisms remain unclear. Herein, we aim to determine the role of hypoxia-inducible lipid droplet associated protein (HILPDA)/hypoxia-inducible gene 2 (HIG2), a selective inhibitor of intracellular lipolysis, in NASH-driven HCC. The clinical significance of HILPDA was assessed in human NASH-driven HCC specimens by immunohistochemistry and transcriptomics analyses. The oncogenic effect of HILPDA was assessed in human HCC cells and in 3D epithelial spheroids upon exposure to free fatty acids and either normoxia or hypoxia. Lipidomics profiling of wild-type and HILPDA knockout HCC cells was assessed via shotgun and targeted approaches. Wild-type (Hilpdafl/fl) and hepatocyte-specific Hilpda knockout (HilpdaΔHep) mice were fed a Western diet and high sugar in drinking water while receiving carbon tetrachloride to induce NASH-driven HCC. In patients with NASH-driven HCC, upregulated HILPDA expression is strongly associated with poor survival. In oxygen-deprived and lipid-loaded culture conditions, HILPDA promotes viability of human hepatoma cells and growth of 3D epithelial spheroids. Lack of HILPDA triggered flux of polyunsaturated fatty acids to membrane phospholipids and of saturated fatty acids to ceramide synthesis, exacerbating lipid peroxidation and apoptosis in hypoxia. The apoptosis induced by HILPDA deficiency was reversed by pharmacological inhibition of ceramide synthesis. In our experimental mouse model of NASH-driven HCC, HilpdaΔHep exhibited reduced hepatic steatosis and tumorigenesis but increased oxidative stress in the liver. Single-cell analysis supports a dual role of hepatic HILPDA in protecting HCC cells and facilitating the establishment of a pro-tumorigenic immune microenvironment in NASH. Hepatic HILPDA is a pivotal oncometabolic factor in the NASH liver microenvironment and represents a potential novel therapeutic target. Non-alcoholic steatohepatitis (NASH, chronic metabolic liver disease caused by buildup of fat, inflammation and damage in the liver) is emerging as the leading risk factor and the fastest growing cause of hepatocellular carcinoma (HCC), the most common form of liver cancer. While curative therapeutic options exist for HCC, it frequently presents at a late stage when such options are no longer effective and only systemic therapies are available. However, systemic therapies are still associated with poor efficacy and some side effects. In addition, no approved drugs are available for NASH. Therefore, understanding the underlying metabolic alterations occurring during NASH-driven HCC is key to identifying new cancer treatments that target the unique metabolic needs of cancer cells.

Identification of novel immune ferroptosis-related genes associated with clinical and prognostic features in breast cancer.

Introduction: Breast cancer is the most common form of cancer among women, it is critical to identify potential targets and prognostic biomarkers. Ferroptosis combined with immunity shows a pivotal role in a variety of tumors, which provides new opportunities to detect and treat breast cancer. Methods: Our first step was to combine multiple datasets to search for immune ferroptosis-related mRNAs. In the next step, risk signatures were created using Least Absolute Shrinkage and Selection Operator (LASSO). After that, based on the results of the multivariate Cox analysis, we created a prognostic nomogram and validated the model's accuracy. Finally, functional enrichment analysis, single sample gene set enrichment analysis (ssGSEA), immunity and drug sensitivity correlation analysis were performed to explore the possible mechanisms by which these immune ferroptosis associated mRNAs affect BRCA survival. Results: An immune ferroptosis signature (IFRSig) consisting of 5 mRNAs was constructed and showed excellent predictability in the training and validation cohorts. A correlation analysis revealed that clinical characteristics were closely related to risk characteristics. Our nomogram model, which we created by combining risk characteristics and clinical parameters, was proven to be accurate at predicting BRCA prognosis. Further, we divided patients into lowrisk and high-risk groups based on the expression of the model-related genes. Compared with low-risk group, high-risk group showed lower levels of immune cell infiltration, immune-related functions, and immune checkpoints molecules, which may associate with the poor prognosis. Discussion: The IFRSig could be used to predict overall survival (OS) and treatment response in BRCA patients and could be viewed as an independent prognostic factor. The findings in this study shed light on the role of immune ferroptosis in the progression of BRCA.

Immunotherapy and Immune Infiltration in Patients with Clear Cell Renal Cell Carcinoma: A Comprehensive Analysis.

On a global scale, renal cell carcinoma (RCC) is the second most common form of cancer and the 10th leading cause of cancer-related deaths. There are about 70% of cases of RCC that are clear cell renal cell carcinomas (ccRCCs). This study explores possible targets for immune therapy in patients with RCC. In the recent years, immunotherapy has been applied to RCC patients. In order to identify genes that are closely associated with immune cells, a weighted gene coexpression network analysis (WGCNA) was conducted. A close association was found between genes involved in MEred and M0 macrophages, M1 macrophages, and M2 macrophages. A prognostic prediction model is subsequently developed by incorporating the OS and the expression level of key genes from the RCC cohort into a univariate COX regression analysis, a multivariate COX regression analysis, and a combined COX regression analysis. We finally discovered that 6 genes are closely associated with the prognosis of RCC patients, including SLC16A12, SLC2A9, IGF2BP2, EMX2, ANK3, and METTL7A. The survival analysis proved the prognostic prediction value of the model. The 1-year, 3-year, and 5-year AUC of ROC curves are 0.759, 0.723, and 0.733, respectively. For clinical ROC curves, the AUC score for risk score, stage, grade, and T stage is 0.759, 0.824, 0722, and 0.736, respectively. The nomogram was constructed for better prognosis prediction of RCC patients. In addition, GSVA and GO enrichment analysis was performed to explore the potential pathways that are closely associated with genes involved in the prognostic prediction model. Accordingly, our study demonstrates that immune cells play a crucial role in RCC infiltration. The development of a prognostic prediction model is a potential new prognostic biomarker and potential immunotherapy target for tumors.

Transcriptome analysis reveals differences in cell cycle, growth and migration related genes that distinguish fibroblasts derived from pre-invasive and invasive breast cancer.

As the most common form of pre-invasive breast cancer, ductal carcinoma in situ (DCIS) affects over 50,000 women in the US annually. Despite standardized treatment involving lumpectomy and radiation therapy, up to 25% of patients with DCIS experience disease recurrence often with invasive ductal carcinoma (IDC), indicating that a subset of patients may be under-treated. As most DCIS cases will not progress to invasion, many patients may experience over-treatment. By understanding the underlying processes associated with DCIS to IDC progression, we can identify new biomarkers to determine which DCIS cases may become invasive and improve treatment for patients. Accumulation of fibroblasts in IDC is associated with disease progression and reduced survival. While fibroblasts have been detected in DCIS, little is understood about their role in DCIS progression. We sought to determine 1) whether DCIS fibroblasts were similar or distinct from normal and IDC fibroblasts at the transcriptome level, and 2) the contributions of DCIS fibroblasts to breast cancer progression. Fibroblasts underwent transcriptome profiling and pathway analysis. Significant DCIS fibroblast-associated genes were further analyzed in existing breast cancer mRNA databases and through tissue array immunostaining. Using the sub-renal capsule graft model, fibroblasts from normal breast, DCIS and IDC tissues were co-transplanted with DCIS.com breast cancer cells. Through transcriptome profiling, we found that DCIS fibroblasts were characterized by unique alterations in cell cycle and motility related genes such as PKMYT1, TGF-α, SFRP1 and SFRP2, which predicted increased cell growth and invasion by Ingenuity Pathway Analysis. Immunostaining analysis revealed corresponding increases in expression of stromal derived PKMYT1, TGF-α and corresponding decreases in expression of SFRP1 and SFRP2 in DCIS and IDC tissues. Grafting studies in mice revealed that DCIS fibroblasts enhanced breast cancer growth and invasion associated with arginase-1+ cell recruitment. DCIS fibroblasts are phenotypically distinct from normal breast and IDC fibroblasts, and play an important role in breast cancer growth, invasion, and recruitment of myeloid cells. These studies provide novel insight into the role of DCIS fibroblasts in breast cancer progression and identify some key biomarkers associated with DCIS progression to IDC, with important clinical implications.