Mihnea P. Dragomir

• MD PhD
• Medical Doctor at Charité Universitätsmedizin Berlin

The mutational landscape of phylogenetically ultraconserved elements (UCEs), especially those in noncoding DNAs (ncUCEs), and their functional relevance in cancers remain poorly characterized. Here, we perform a systematic analysis of whole-genome and in-house targeted UCE sequencing datasets from more than 3000 patients with cancer of 13,736 UCEs...

Background We have recently constructed a DNA methylation classifier that can discriminate between pancreatic ductal adenocarcinoma (PAAD) liver metastasis and intrahepatic cholangiocarcinoma (iCCA) with high accuracy (PAAD-iCCA-Classifier). PAAD is one of the leading causes of cancer of unknown primary and diagnosis is based on exclusion of other...

Patient-Derived Organoids (PDOs) represent a promising technology for therapy prediction in pancreatic cancer, with the potential of enhancing treatment outcomes and allowing more effective, personalized treatment choices. However, classification approaches into sensitive and resistant models remain very variable and are based on single-agent testi...

BACKGROUND Tumor-associated macrophages (TAMs) have been demonstrated to play an important role in the growth and progression of multiple types of cancer, including glioblastoma. The aim of this study is to evaluate the distribution of CD68 and CD163 markers for TAMs in glioma samples and to determine their impact on survival. MATERIAL AND METHODS...

Diagnostic performance of molecular markers in surrogate tissues like stool may be affected by colorectal cancer (CRC) morphological heterogeneity. The mucinous histotype represents a subgroup of CRC with a peculiar molecular program and unfavorable disease progression. However, the percentage of mucinous morphology necessary to define this subtype...

The diagnostic performance of molecular markers in surrogate tissues like stool may be affected by colorectal cancer (CRC) morphological heterogeneity. The mucinous histotype represents a subgroup of CRC with a peculiar molecular program and unfavorable disease progression. However, the percentage of mucinous morphology necessary to define this sub...

Background Tumor embolism is a very rare primary manifestation of cancers and the diagnosis is challenging, especially if located in the pulmonary arteries, where it can mimic nonmalignant pulmonary embolism. Intimal sarcoma is one of the least commonly reported primary tumors of vessels with only a few cases reported worldwide. A typical location...

Morphologic heterogeneity of colorectal adenocarcinoma (CRC) is poorly understood. Previously, we identified morphological patterns associated with CRC molecular subtypes, and showed that these patterns have distinct molecular motifs (Budinska et al., 2023). Here, we evaluated the heterogeneity of these patterns across CRC. Three pathologists evalu...

Over the past decade, there have been reports of short novel functional peptides (less than 100 aa in length) translated from so-called non-coding RNAs (ncRNAs) that have been characterized using mass spectrometry (MS) and large-scale proteomics studies. Therefore, understanding the bivalent functions of some ncRNAs as transcripts that encode both...

Background: Thyroid transcription factor 1 (TTF-1) is expressed in 70% to 80% of lung adenocarcinomas (LUAD). Several papers revealed that TTF-1 expression is associated with better patient outcomes independent of the tumor stage. However, it is unknown whether the prognostic impact of TTF-1 only results from a different growth pattern (tumor gradi...

Background: Despite the rapidly increasing number of new targeted and immunotherapeutic options over the past two decades, the prognosis of patients with NSCLC, even with early-stage tumors, is still poor and novel biomarkers are needed to better stratify patients in terms of survival and treatment response. A novel approach is to gain a holistic u...

Introduction: The metastasis of a pancreatic ductal adenocarcinoma (PAAD) is a diagnosis of exclusion and one of the most common causes of cancer of unknown primary (CUP). We have recently developed a genome-wide DNA methylation-based neural network classifier that can accurately differentiate between liver metastasis of a PAAD and intrahepatic cho...

The combination of toripalimab (an anti-PD-1 antibody) with definitive chemoradiotherapy (CRT) demonstrated encouraging efficacy against locally advanced esophageal squamous cell carcinoma (ESCC) in the EC-CRT-001 phase II trial (NCT04005170). The primary endpoint of this trial was the clinical complete response rate (cCR), and the secondary endpoi...

Background The aim of this study was to analyse transcriptomic differences between primary and recurrent high-grade serous ovarian carcinoma (HGSOC) to identify prognostic biomarkers. Methods We analysed 19 paired primary and recurrent HGSOC samples using targeted RNA sequencing. We selected the best candidates using in silico survival and pathway...

The prognostic role of tumor cells in pancreatic ductal adenocarcinoma (PDAC) of the pancreatic head with direct microscopic infiltration (DMI) or in close proximity (≤1 mm) to the resection margin (RM) remains unclear. This single-center, retrospective study included specimens from 75 patients who underwent oncological resection of pancreatic head...

Purpose This study describes the morphologic and phenotypic spatial heterogeneity of tumor cells and the tissue microenvironment (TME), focusing on immune infiltration in OSCCs. Study design Patients with OSCCs and planned surgical tumor resection were eligible for the study. Two biopsies each from the tumor center and the tumor rim were obtained....

Heterogeneity of colorectal carcinoma (CRC) represents a major hurdle towards personalized medicine. Efforts based on whole tumor profiling demonstrated that the CRC molecular subtypes were associated with specific tumor morphological patterns representing tumor subregions. We hypothesize that whole-tumor molecular descriptors depend on the morphol...

Currently, surgeons deal with an older patient cohort, confronting new challenges brought by the raised life expectancy. This population is unrepresented in surgical trials; therefore, the optimal therapy is still a matter of debate. The efficacy of open versus minimal invasive management of colorectal cancer (CRC) in an elderly cohort is not clear...

Background Non-small-cell lung cancer (NSCLC) is the leading cause for cancer death. Current targeted- and immuno-therapies are effective in a patient subset, but causes for resistance and the complexity of the immune reaction are difficult to be identified on a single patient level. It is hypothesized that the tumor microenvironment (TME) and its...

Heterogeneity of colorectal carcinoma (CRC) represents a major hurdle towards personalized medicine. Efforts based on whole tumor profiling demonstrated that the CRC molecular subtypes were associated with specific tumor morphological patterns representing tumor subregions. We hypothesize that whole- tumor molecular descriptors depend on the morpho...

Background The enzyme indoleamine 2,3-dioxygenase 1 (IDO1) plays a crucial role in regulating the immune system's response to tumors, but its exact role in cancer, especially in high-grade serous ovarian cancer (HGSOC), remains controversial. We aimed to investigate the prognostic impact of IDO1 expression and its correlation with tumor-infiltratin...

Background Mechanisms of development and progression of high-grade serous ovarian cancer (HGSOC) are poorly understood. EVI1 and PARP1, part of TGF-ß pathway, are upregulated in cancers with DNA repair deficiencies with DNA repair deficiencies and may influce disease progression and survival. Therefore we questioned the prognostic significance of p...

The combination of toripalimab (an anti-PD-1 antibody) with definitive chemoradiotherapy (CRT) demonstrated encouraging efficacy against locally advanced esophageal squamous cell carcinoma (ESCC) in the EC-CRT-001 phase II trial. This exploratory analysis evaluated the role of circulating tumor DNA (ctDNA) and blood-based tumor mutational burden (b...

Heterogeneity of colorectal carcinoma (CRC) represents a major hurdle towards personalized medicine. Efforts based on whole tumor profiling demonstrated that the CRC molecular subtypes were associated with specific tumor morphological patterns representing tumor subregions. We hypothesize that whole-tumor molecular descriptors depend on the morphol...

Heterogeneity of colorectal carcinoma (CRC) represents a major hurdle towards personalized medicine. Efforts based on whole tumor profiling demonstrated that the CRC molecular subtypes were associated with specific tumor morphological patterns representing tumor subregions. We hypothesize that whole-tumor molecular descriptors depend on the morphol...

Background: Differentiating intrahepatic cholangiocarcinomas (iCCA) from hepatic metastases of pancreatic ductal adenocarcinoma (PAAD) is challenging. Both tumours have similar morphological and immunohistochemical pattern and share multiple driver mutations. We hypothesised that DNA methylation-based machine-learning algorithms may help perform t...

Sepsis remains a leading cause of human death and currently has no pathogenesis-specific therapy. Hampered progress is partly due to a lack of insight into deep mechanistic processes. In the last decade, deciphering the functions of small non-coding microRNAs (miRNAs) in sepsis pathogenesis became a dynamic research topic. To screen for new miRNA t...

The causes and consequences of abnormal biogenesis of extracellular vesicles (EVs) are not yet well understood in malignancies, including in breast cancers (BCs). Given the hormonal signaling dependence of estrogen receptor-positive (ER+) BC, we hypothesized that 17β-estradiol (estrogen) might influence EV production and microRNA (miRNA) loading. W...

Background: Molecular bladder cancer (BC) subtypes define distinct biological entities and were shown to predict treatment response in neoadjuvant and adjuvant settings. The extent of intratumoral heterogeneity (ITH) might affect subtyping of individual patients. Objective: To comprehensively assess the ITH of molecular subtypes in a cohort of musc...

Background: Ultraconserved regions or elements (UCEs) are greater than 100-base pairs in length and are perfectly (100%) conserved across large evolutionary distances in the genomes of at least 3 of 5 placental mammals: human, cow, dog, rat, and mouse. Most UCEs are located in non-coding regions of the genome; however, some UCEs overlap with coding...

Accuracy and transparency of scientific data are becoming more and more relevant with the increasing concern regarding the evaluation of data reproducibility in many research areas. This concern is also true for quantifying coding and non-coding RNAs, with the remarkable increase in publications reporting RNA profiling and sequencing studies. To ad...

Heterogeneity of colorectal carcinoma (CRC) represents a major hurdle towards personalized medicine. Efforts based on whole tumor profiling demonstrated that the CRC molecular subtypes were associated with specific tumor morphological patterns representing tumor subregions. We hypothesize that molecular descriptors depend on morphological heterogen...

Immune checkpoint therapy (ICT) has shown promising potential in the treatment of multiple solid tumors. However, the role of ICT in pancreatic ductal adenocarcinoma (PDAC) remains limited. Patterns of immune checkpoints (ICs) in PDAC represent the basis for establishing a potent ICT. The aim of this study is to create a profile of IC expression an...

Background Bladder cancer (BC) has the highest per-patient cost of all cancer types. Hence, we aim to develop a non-invasive, point-of-care tool for the diagnostic and molecular stratification of patients with BC based on combined microRNAs (miRNAs) and surface-enhanced Raman spectroscopy (SERS) profiling of urine. Methods Next-generation sequenci...

Gastrointestinal cancers account for 22.5% of cancer related deaths worldwide and represent circa 20% of all cancers. In the last decades, we have witnessed a shift from histology-based to molecular-based classifications using genomic, epigenomic, and transcriptomic data. The molecular based classification revealed new prognostic markers and may ai...

Background Neoadjuvant chemoradiotherapy followed by esophagectomy is the standard treatment for patients with locally advanced esophageal squamous cell carcinoma (ESCC). This study explored correlations of clinical factors and dose-volume histogram (DVH) parameters with postoperative cardiopulmonary complications and predicted their risk by establ...

Background Proton pump inhibitors (PPIs) have been shown to regulate the gut microbiome and affect the response to immune checkpoint inhibitors (ICIs). Contradictory results on survival have been observed in patients concomitantly treated with ICIs and PPIs. We performed a systematic review and meta-analysis to determine the association between PPI...

2613 Background: Proton pump inhibitors (PPIs) were revealed to regulate gut microbiome alterations and further impact the response to immune checkpoint inhibitors (ICIs). Contradictory impacts on survival were observed in ICI-treated patients when concomitantly use PPI or not. We performed this systematic review and meta-analysis to analyze the as...

It is now well known that non-coding RNAs (ncRNAs), rather than protein-coding transcripts, are the preponderant RNA transcripts. NcRNAs, particularly microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are widely appreciated as pervasive regulators of multiple cancer hallmarks such as proliferation, apoptosis, invasio...

Renal cancer (RC) represents 3% of all cancers, with a 2% annual increase in incidence worldwide, opening the discussion about the need for screening. However, no established screening tool currently exists for RC. To tackle this issue, we assessed surface-enhanced Raman scattering (SERS) profiling of serum as a liquid biopsy strategy to detect ren...

Simple Summary Due to the rising burden of pancreatic cancer and poor outcomes, a precise, post-operative cancer staging for further and individualized therapy is needed. In the latest cancer classification system, the lymph node invasion mechanism is not addressed. Due to different outcomes regarding the lymph node invasion, we suggest a rethinkin...

Alterations in microRNAs (miRNAs) expression are causative in the initiation and progression of human cancers. The molecular events responsible for the widespread differential expression of miRNAs in malignancy are exemplified by their location in cancer-associated genomic regions, epigenetic mechanisms, transcriptional dysregulation, chemical modi...

Surface-enhanced Raman scattering (SERS) is emerging as a novel strategy for biofluid analysis. In this review, we delineate four experimental SERS protocols that are frequently used for the profiling of biofluids: 1) liquid SERS for the detection of purine metabolites; 2) iodide-modified liquid SERS for the detection of proteins; 3) dried SERS for...

Cancer is a devastating disease and has recently become the leading cause of death in western countries, representing an immense public health burden. When it comes to cancer treatment, chemotherapy is one of the main pillars, especially for advanced stage tumors. Over the years, natural compounds have emerged as one of the most valuable resources...

The solid tumor microenvironment includes nerve fibers that arise from the peripheral nervous system. Recent work indicates that newly formed adrenergic nerve fibers promote tumor growth, but the origin of these nerves and the mechanism of their inception are unknown. Here, by comparing the transcriptomes of cancer-associated trigeminal sensory neu...

Knockout (KO) of long non-coding RNAs (lncRNAs) enables functional characterization of this still poorly described group of transcripts. One of the most efficient and simplest methods to achieve complete KO of a lncRNA is by employing CRISPR/Cas gene editing. As most lncRNAs are not well annotated, their individual functional regions are often not...

In this study we aimed to develop nomogram models for predicting the overall survival (OS) and cancer-specific survival (CSS) of patients with metaplastic breast cancer (MBC). Data of patients diagnosed with MBC from 1973 to 2015 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox ana...

Objectives Studies on the coronavirus disease 2019 (COVID-19) usually focus on middle aged and older adults. However, younger patients may present with severe COVID-19 and potentially fatal outcomes. For optimized, more specialized therapeutic regimens in this particular patient group, a better understanding of underlying pathomechanisms is of utte...

Background: The mechanisms that induce immunodeficiency after splenectomy remain unknown. The aim of this study was to measure the cytokine releasing capacity of the whole blood as an expression of the innate immunity after total (TS) and subtotal/partial splenectomy (S/PS) in order to assess the impact of splenectomy on the individual cytokine re...

Background and purpose: Despite definitive chemoradiotherapy (CRT) being a recommended therapeutic method for patients with T4b esophageal squamous cell carcinoma (ESCC), treatment response and the complication remain unclear. Esophageal fistula is a severe CRT-related complication when treating locally advanced ESCC, but data on risk factors that...

The study by Zagorac and colleagues represents an important step forward in the field of breast cancer, explaining a novel molecular mechanism of transition from slowly multiplying tumor-initiating cells (TIC) into their more differentiated version characterized by high proliferation. The mechanism involves the transcription factors SOX2 and EZH2,...

Currently, for seemingly every type of cancer, dysregulated levels of non-coding RNAs (ncRNAs) are reported and non-coding transcripts are expected to be the next class of diagnostic and therapeutic tools in oncology. Recently, alterations to the ncRNAs transcriptome have emerged as a novel hallmark of cancer. Historically, ncRNAs were characterize...

Background Metaplastic breast cancer (MBC) is a rare type of breast cancer with an increasing incidence, we aim to develop clinical nomograms to predict the overall survival and cancer-specific survival for patients with MBC. Methods Patients data were collected from the SEER database between 1973 and 2015. All included patients were randomly assig...

Primary myelofibrosis (PMF) is a pluripotent hematopoietic stem cell-derived malignancy, included in the heterogeneous group of myeloproliferative neoplasms (MPNs). PMF diagnosis is based on a composite assessment of clinical and laboratory data. The three major diagnostic criteria are: screening for driver mutations, exclusion of other conditions...

The ability of a receptor to preferentially activate only a subset of available downstream signal cascades is termed biased signaling. Although comprehensively recognized for the G protein–coupled receptors (GPCR), this process is scarcely explored downstream of receptor tyrosine kinases (RTK), including the cancer-relevant insulin-like growth fact...

One of the limitations of cancer research has been the restricted focus on tumor cells and the omission of other non-malignant cells that are constitutive elements of this systemic disease. Current research is focused on the bidirectional communication between tumor cells and other components of the tumor microenvironment (TME), such as immune and...

Background Metaplastic breast cancer (MBC) is a rare type of breast cancer with an increasing incidence, we aim to develop clinical nomograms to predict the overall survival and cancer-specific survival for patients with MBC. Methods Patients data were collected from the SEER database between 1973 and 2015. All included patients were randomly assig...

Non-coding RNAs (ncRNAs) are essential players in many cellular processes, from normal development to oncogenic transformation. Initially, ncRNAs were defined as transcripts that lacked an open reading frame (ORF). However, multiple lines of evidence suggest that certain ncRNAs encode small peptides of less than 100 amino acids. The sequences encod...

Background & Aims Chromosomal instability (CIN) is a carcinogenesis event that promotes metastasis and resistance to therapy, by unclear mechanisms. Expression of the colon cancer associated transcript 2 gene (CCAT2), which encodes a long noncoding RNA (lncRNA), associates with CIN, but little is known about how CCAT2 lncRNA regulates this cancer e...

The generation and organization of the invasion front shape of neoplasms is an intriguing problem. The intimate mechanism is not yet understood, but the prevailing theory is that it represents an example of morphogenesis. Morphogenesis requires the presence of specific molecules, known as morphogens (activators and inhibitors), which can diffuse an...

Bladder cancer (BC) is the tenth most frequent cancer worldwide. Due to the need for recurrent cystoscopies and the lack of non-invasive biomarkers, BC is associated with a high management burden. In this respect, small non-coding RNAs (sncRNAs) have been investigated in urine as possible biomarkers for BC, but in plasma their potential has not yet...

Background Hereditary spherocytosis (HS) is a common inherited disease affecting the erythrocyte membrane. Total splenectomy (TS) is effective in reducing hemolysis and decreasing the need of transfusions, but total removal of the spleen represents a potential risk factor for infectious and non-infectious complications. On the other hand, subtotal...

As one of the most recently (re)discovered types of non-coding RNAs (ncRNA), circular RNAs (circRNAs) differentiate from other ncRNAs by a specific biogenesis, high stability, and distinct functions. The biogenesis of circRNAs can be categorized into three mechanisms that permit the back-splicing reaction: exon-skipping, pairing of neighboring intr...

The solid tumour microenvironment includes nerve fibres that arise from the peripheral nervous system1,2. Recent work indicates that newly formed adrenergic nerve fibres promote tumour growth, but the origin of these nerves and the mechanism of their inception are unknown1,3. Here, by comparing the transcriptomes of cancer-associated trigeminal sen...

One of the most unexpected discoveries in molecular oncology, in the last decades, was the identification of a new layer of protein coding gene regulation by transcripts that do not codify for proteins, the non-coding RNAs. These represent a heterogeneous category of transcripts that interact with many types of genetic elements, including regulator...

Objective To investigate the function of a novel primate-specific long non-coding RNA (lncRNA), named FLANC, based on its genomic location (co-localised with a pyknon motif), and to characterise its potential as a biomarker and therapeutic target. Design FLANC expression was analysed in 349 tumours from four cohorts and correlated to clinical data...

Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by cytopenia and extramedullary hematopoiesis, resulting in splenomegaly. Multiple pathological mechanisms (e.g., circulating cytokines and genetic alterations, such as JAKV617F mutation) have been implicated in the etiology of MF, but the molecular mechanism causing resistance to JA...

One of the major challenges in oncology is drug resistance, which triggers relapse and shortens patients’ survival. In order to promote drug desensitization, cancer cells require the establishment of an ideal tumor microenvironment that accomplishes specific conditions. To achieve this objective, cellular communication is a key factor. Classically,...

Background: Because of the complexity of the blood-brain barrier (BBB), brain tumors, especially the most common and aggressive primary malignant tumor type arising from the central nervous system (CNS), glioblastoma, remain an essential challenge regarding diagnostic and treatment. There are no approved circulating diagnostic or prognostic biomar...

Background Central pancreatectomy (CP) is the alternative to distal pancreatectomy (DP) for specific pathologies of the mid-pancreas. However, the benefits of CP over DP remain controversial. This study aims to compare the two procedures by conducting a meta-analysis of all published papers. Methods A systematic search of original studies comparin...

Cancer is one of the most frequent and devastating diseases. Previous reports have shown that radio and chemo-resistant cancer stem cell (CSC) population is primarily responsible for cancer recurrences after radiotherapy and chemotherapy. Other studies demonstrated that Lissencephaly-1 (LIS1) protein, also known as platelet activating factor acetyl...

Background: Only few studies, with small patient cohorts, have evaluated the effect of radiotherapy (RT) for metaplastic breast cancer (MBC). Hence, it is important to investigate the role of RT in MBC survival using a large population-database. Methods: A retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER) fr...

Splenectomy is a common surgical procedure performed in millions of people worldwide. Epidemiologic data show that splenectomy is followed by infectious (sepsis) and non‐infectious complications, with unknown mechanisms. In order to explore the role of the non‐coding transcripts involved in these complications, we analysed a panel of circulating mi...

A very expensive research was carried out in the last decades to understand the molecular physiology of cancer cells, and despite of this, cancer remains one of the leading causes of death in the world. Cancer research was focused, for decades, mainly on protein-coding genes, and only recently research shifted toward the noncoding component of the...

Richter syndrome is the name given to the transformation of the most frequent type of leukemia, chronic lymphocytic leukemia, into an aggressive lymphoma. Patients with Richter syndrome have limited response to therapies and dismal survival. The underlying mechanisms of transformation are insufficiently understood and there is a major lack of knowl...

[This corrects the article DOI: 10.3389/fonc.2018.00179.].

MicroRNAs (miRNAs) are synonymous with post-transcriptional repression of target genes. A number of studies, however, have reported miRNAs functioning outside this paradigm, and this SnapShot outlines these unconventional ways in which miRNAs can exert regulatory functions. To view this SnapShot, open or download the PDF. MicroRNAs (miRNAs) are syn...

Hereditary spherocytosis (HS) is a common inherited hemolytic anemia caused by a defective erythrocyte cellular membrane. Irrespective of type of surgery performed, several case reports comparing the two type of procedures, have not proven any significant difference between serum bilirubin, serum hemoglobin, red blood cells' and platelets' count, i...