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Myelodysplastic neoplasm (MDS) is a heterogeneous group of clonal hematological disorders that originate from the hematopoietic and progenitor cells and present with cytopenias and morphologic dysplasia with a propensity to progress to bone marrow failure or acute myeloid leukemia (AML). Genetic evolution plays a critical role in the pathogenesis, progression, and clinical outcomes of MDS. This process involves the acquisition of genetic mutations in stem cells that confer a selective growth advantage, leading to clonal expansion and the eventual development of MDS. With the advent of next-generation sequencing (NGS) assays, an increasing number of molecular aberrations have been discovered in recent years. The knowledge of molecular events in MDS has led to an improved understanding of the disease process, including the evolution of the disease and prognosis, and has paved the way for targeted therapy. The 2022 World Health Organization (WHO) Classification and the International Consensus Classification (ICC) have incorporated the molecular signature into the classification system for MDS. In addition, specific germline mutations are associated with MDS development, especially in pediatrics and young adults. This article reviews the genetic abnormalities of MDS in adults with a brief review of germline predisposition syndromes.

With the invention of high-throughput screening technologies, innumerable drug sensitivity data for thousands of cancer cell lines and hundreds of compounds have been produced. Computational analysis of these data has opened a new horizon in the development of novel anti-cancer drugs. Previous deep-learning approaches to predict drug sensitivity showed drawbacks due to the casual integration of genomic features of cell lines and compound chemical features. The challenges addressed include the intricate interplay of diverse molecular features, interpretability of complex deep learning models, and the optimization of drug combinations for synergistic effects. Through the utilization of normalized discounted cumulative gain (NDCG) and root mean squared error (RMSE) as evaluation metrics, the models aim to concurrently assess the ranking quality of recommended drugs and the accuracy of predicted drug responses. The integration of the DRPO model into cancer drug response prediction not only tackles these challenges but also holds promise in facilitating more effective, personalized, and targeted cancer therapies. This paper proposes a new deep learning model, DRPO , for efficient integration of genomic and compound features in predicting the half maximal inhibitory concentrations (IC50). First, matrix factorization is used to map the drug and cell line into latent 'pharmacogenomic' space with cell line-specific predicted drug responses. Using these drug responses, we next obtained the essential drugs using a Normalized Discounted Cumulative Gain (NDCG) score. Finally, the essential drugs and genomic features are integrated to predict drug sensitivity using a deep model. Experimental results with RMSE 0.39 and NDCG 0.98 scores on Genomics of drug sensitivity in cancer (GDSC1) datasets show that our proposed approach has outperformed the previous approaches, including DeepDSC, CaDRRes, and KMBF. These good results show great potential to use our new model to discover novel anti-cancer drugs for precision medicine. [ABSTRACT FROM AUTHOR]

With the invention of high-throughput screening technologies, innumerable drug sensitivity data for thousands of cancer cell lines and hundreds of compounds have been produced. Computational analysis of these data has opened a new horizon in the development of novel anti-cancer drugs. Previous deep-learning approaches to predict drug sensitivity showed drawbacks due to the casual integration of genomic features of cell lines and compound chemical features. The challenges addressed include the intricate interplay of diverse molecular features, interpretability of complex deep learning models, and the optimization of drug combinations for synergistic effects. Through the utilization of normalized discounted cumulative gain (NDCG) and root mean squared error (RMSE) as evaluation metrics, the models aim to concurrently assess the ranking quality of recommended drugs and the accuracy of predicted drug responses. The integration of the DRPO model into cancer drug response prediction not only tackles these challenges but also holds promise in facilitating more effective, personalized, and targeted cancer therapies. This paper proposes a new deep learning model, DRPO, for efficient integration of genomic and compound features in predicting the half maximal inhibitory concentrations (IC50). First, matrix factorization is used to map the drug and cell line into latent ’pharmacogenomic’ space with cell line-specific predicted drug responses. Using these drug responses, we next obtained the essential drugs using a Normalized Discounted Cumulative Gain (NDCG) score. Finally, the essential drugs and genomic features are integrated to predict drug sensitivity using a deep model. Experimental results with RMSE 0.39 and NDCG 0.98 scores on Genomics of drug sensitivity in cancer (GDSC1) datasets show that our proposed approach has outperformed the previous approaches, including DeepDSC, CaDRRes, and KMBF. These good results show great potential to use our new model to discover novel anti-cancer drugs for precision medicine.

Medulloblastomas are the most common malignant brain tumors in the pediatric population. Based on the idea that tumors with identical radio-genomic features should behave similarly, the 4 molecular subtypes are now widely accepted as a guide for the management and prognosis. The radiological features of medulloblastomas can predict the molecular subtype; thus, anticipating the subsequent disease progression. However, this has not been evaluated comprehensively. We aim to thoroughly study the association between the molecular subtypes and radiological features of medulloblastomas. Moreover, we aim to investigate the efficacy of this correlation with the use of progression-free survival and 5-year survival rates. A retrospective analysis was conducted for all histopathological confirmed medulloblastomas in pediatric patients (<16 years old) that were operated on in Kuwait over the past ten years (n = 44). The radiological, histological, and molecular characteristics were justifiably evaluated and analyzed in our sample. The overall progression-free survival after one year was noticed among 27 cases (≈44%) and the nonspecific 5-year survival was seen in 31 cases (≈70%) after a 5-year follow-up. Sonic Hedgehog and Wingless had the best outcomes, while group 3 showed the worst outcomes. Our findings did not support the association between most of the typical magnetic resonance imaging characteristics and survival rate. We further established that Sonic Hedgehog and Wingless biological types have a better prognosis. There was no association observed between the radiographic features, specifically the location, and the molecular subtype. [ABSTRACT FROM AUTHOR]

Background: Microsatellite instability-high (MSI-H) tumors are distinct molecular subtypes in gastric cancer. However, a few studies have comprehensively reported the molecular features of MSI-H tumors and their prognostic factors in locally advanced gastric cancer. This study aimed to clarify the molecular features and prognostic factors of locally advanced MSI-H gastric cancer. Methods: This study included 499 patients with locally advanced gastric cancer who underwent radical gastrectomy. We evaluated the MSI status and compared with previously published whole-exome sequencing, panel sequencing, and gene expression profiling data. Clinicopathological characteristics and molecular profiles were compared between patients with MSI-H and microsatellite stable (MSS) gastric cancer. A subgroup analysis of survival was performed in patients with MSI-H gastric cancer. Results: MSI-H tumors were detected in 79 of 499 patients (15.8%). MSI-H tumors were associated with an increased tumor mutational burden, MLH1 downregulation, CD274 (PD-L1) upregulation, and enrichment of cell cycle pathways. Among patients with MSI-H gastric cancer, the disease-specific survival (DSS) tended to be better in the surgery plus tegafur, gimeracil, and oteracil potassium (S-1) adjuvant chemotherapy group than in the surgery alone group, especially for stage III patients. Furthermore, DSS was better in the T cell-inflamed gene expression signature-high group, and it tended to be worse in the non-solid type poorly differentiated adenocarcinoma group. Conclusions: The molecular features and prognostic factors of locally advanced MSI-H gastric cancer were clarified. S-1 adjuvant chemotherapy appears to be beneficial, and the T cell-inflamed gene expression signature and histopathological type are prognostic factors in MSI-H tumors. [ABSTRACT FROM AUTHOR]

Objective To investigate the clinicopathological and molecular features of appendiceal mucinous neoplasms (AMNs), compare the differences bewteen the LAMN and HAMN. Methods 32 cases of AMNs were collected between January 2015 and September 2021. They were hospitalized in the Affiliated Hospital of Southwest Medical University. 10 samples of them were selected for Next Generation Sequencing (NGS) analysis of 425 genes. Results The majority of AMNs were female (68.8%) . Most patients had positive tumor markers. The proportion of distant metastasis, recurrence and death in HAMN patients were higher than those in LAMN patients. KRAS, GNAS and BRAF gene mutations were common in AMNs patients. The SNP of MTHFR and NQO1 were common in AMNs patients. The TMB of LAMN and HAMN patients were both lower, and there was no statistical significance between them ( P > 0.05). Conclusion AMNs have special clinical pathological and molecular pathological changes, but there is no significant difference between HAMN and LAMN. [ABSTRACT FROM AUTHOR]

As one of the most prevalent digestive system tumours, colorectal cancer (CRC) poses a significant threat to global human health. With the emergence of immunotherapy and target therapy, the prognosis for the majority of CRC patients has notably improved. However, the subset of patients with BRAF exon 15 p.V600E mutation (BRAFV600E) has not experienced remarkable benefits from these therapeutic advancements. Hence, researchers have undertaken foundational investigations into the molecular pathology of this specific subtype and clinical effectiveness of diverse therapeutic drug combinations. This review comprehensively summarised the distinctive molecular features and recent clinical research advancements in BRAF‐mutant CRC. To explore potential therapeutic targets, this article conducted a systematic review of ongoing clinical trials involving patients with BRAFV600E‐mutant CRC. [ABSTRACT FROM AUTHOR]

Borderline ovarian tumours (BOTs) show intriguing characteristics distinguishing them from other ovarian tumours. The aim of the systematic review was to analyse the spectrum of molecular changes found in BOTs and discuss their significance in the context of the overall therapeutic approach. The systematic review included articles published between 2000 and 2023 in the databases: PubMed, EMBASE, and Cochrane. After a detailed analysis of the available publications, we qualified for the systematic review: 28 publications on proto-oncogenes: BRAF, KRAS, NRAS, ERBB2, and PIK3CA, 20 publications on tumour suppressor genes: BRCA1/2, ARID1A, CHEK2, PTEN, 4 on adhesion molecules: CADM1, 8 on proteins: B-catenin, claudin-1, and 5 on glycoproteins: E-Cadherin. In addition, in the further part of the systematic review, we included eight publications on microsatellite instability and three describing loss of heterozygosity in BOT. Molecular changes found in BOTs can vary on a case-by-case basis, identifying carcinogenic mutations through molecular analysis and developing targeted therapies represent significant advancements in the diagnosis and treatment of ovarian malignancies. Molecular studies have contributed significantly to our understanding of BOT pathogenesis, but substantial research is still required to elucidate the relationship between ovarian neoplasms and extraneous disease, identify accurate prognostic indicators, and develop targeted therapeutic approaches.

Objective: Mammographic calcifications are a common feature of breast cancer, but their molecular characteristics and treatment implications in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) breast cancer remain unclear. Methods: We retrospectively collected mammography records of an HR+/HER2− breast cancer cohort (n = 316) with matched clinicopathological, genomic, transcriptomic, and metabolomic data. On the basis of mammographic images, we grouped tumors by calcification status into calcification-negative tumors, tumors with probably benign calcifications, tumors with calcification of low-moderate suspicion for maligancy and tumors with calcification of high suspicion for maligancy. We then explored the molecular characteristics associated with each calcification status across multiple dimensions. Results: Among the different statuses, tumors with probably benign calcifications exhibited elevated hormone receptor immunohistochemical staining scores, estrogen receptor (ER) pathway activation, lipid metabolism, and sensitivity to endocrine therapy. Tumors with calcifications of high suspicion for malignancy had relatively larger tumor sizes, elevated lymph node metastasis incidence, Ki-67 staining scores, genomic instability, cell cycle pathway activation, and may benefit from cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors. Conclusions: Our research established links between tumor calcifications and molecular features, thus proposing potential precision treatment strategies for HR+/HER2− breast cancer.

Myelodysplastic neoplasm (MDS) is a heterogeneous group of clonal hematological disorders that originate from the hematopoietic and progenitor cells and present with cytopenias and morphologic dysplasia with a propensity to progress to bone marrow failure or acute myeloid leukemia (AML). Genetic evolution plays a critical role in the pathogenesis, progression, and clinical outcomes of MDS. This process involves the acquisition of genetic mutations in stem cells that confer a selective growth advantage, leading to clonal expansion and the eventual development of MDS. With the advent of next-generation sequencing (NGS) assays, an increasing number of molecular aberrations have been discovered in recent years. The knowledge of molecular events in MDS has led to an improved understanding of the disease process, including the evolution of the disease and prognosis, and has paved the way for targeted therapy. The 2022 World Health Organization (WHO) Classification and the International Consensus Classification (ICC) have incorporated the molecular signature into the classification system for MDS. In addition, specific germline mutations are associated with MDS development, especially in pediatrics and young adults. This article reviews the genetic abnormalities of MDS in adults with a brief review of germline predisposition syndromes.

Abstract Objective This study aims to analyze the molecular characteristics of the novel coronavirus (SARS-CoV-2) Omicron variant BA.2.76 in Jining City, China. Methods Whole-genome sequencing was performed on 87 cases of SARS-CoV-2 infection. Evolutionary trees were constructed using bioinformatics software to analyze sequence homology, variant sites, N-glycosylation sites, and phosphorylation sites. Results All 87 SARS-CoV-2 whole-genome sequences were classified under the evolutionary branch of the Omicron variant BA.2.76. Their similarity to the reference strain Wuhan-Hu-1 ranged from 99.72 to 99.74%. In comparison to the reference strain Wuhan-Hu-1, the 87 sequences exhibited 77–84 nucleotide differences and 27 nucleotide deletions. A total of 69 amino acid variant sites, 9 amino acid deletions, and 1 stop codon mutation were identified across 18 proteins. Among them, the spike (S) protein exhibited the highest number of variant sites, and the ORF8 protein showed a Q27 stop mutation. Multiple proteins displayed variations in glycosylation and phosphorylation sites. Conclusion SARS-CoV-2 continues to evolve, giving rise to new strains with enhanced transmission, stronger immune evasion capabilities, and reduced pathogenicity. The application of high-throughput sequencing technologies in the epidemic prevention and control of COVID-19 provides crucial insights into the evolutionary and variant characteristics of the virus at the genomic level, thereby holding significant implications for the prevention and control of the COVID-19 pandemic.

Objective: This study aims to analyze the molecular characteristics of the novel coronavirus (SARS-CoV-2) Omicron variant BA.2.76 in Jining City, China. Methods: Whole-genome sequencing was performed on 87 cases of SARS-CoV-2 infection. Evolutionary trees were constructed using bioinformatics software to analyze sequence homology, variant sites, N-glycosylation sites, and phosphorylation sites. Results: All 87 SARS-CoV-2 whole-genome sequences were classified under the evolutionary branch of the Omicron variant BA.2.76. Their similarity to the reference strain Wuhan-Hu-1 ranged from 99.72 to 99.74%. In comparison to the reference strain Wuhan-Hu-1, the 87 sequences exhibited 77–84 nucleotide differences and 27 nucleotide deletions. A total of 69 amino acid variant sites, 9 amino acid deletions, and 1 stop codon mutation were identified across 18 proteins. Among them, the spike (S) protein exhibited the highest number of variant sites, and the ORF8 protein showed a Q27 stop mutation. Multiple proteins displayed variations in glycosylation and phosphorylation sites. Conclusion: SARS-CoV-2 continues to evolve, giving rise to new strains with enhanced transmission, stronger immune evasion capabilities, and reduced pathogenicity. The application of high-throughput sequencing technologies in the epidemic prevention and control of COVID-19 provides crucial insights into the evolutionary and variant characteristics of the virus at the genomic level, thereby holding significant implications for the prevention and control of the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

In recent decades, the prevalence of thyroid cancer has risen substantially, with papillary thyroid microcarcinoma (PTMC) constituting over 50% of cases. Although most PTMCs exhibit indolent growth and a favorable prognosis, some present an increased risk of recurrence and an unfavorable prognosis due to high-risk characteristics such as lymph node metastasis, extrathyroidal extension, and distant metastasis. The early identification of clinically progressing PTMC remains elusive. In this review, the authors summarize findings from PTMC progression-related literature, highlighting that factors such as larger tumor size, cervical lymph node metastasis, extrathyroidal extension, younger age, higher preoperative serum thyroid-stimulating hormone levels, family history, and obesity positively correlate with PTMC progression. The role of multifocality in promoting PTMC progression; however, remains contentious. Furthermore, recent studies have shed light on the impact of mutations, such as BRAF and TERT mutations, on PTMC progression. Researchers have identified several mRNAs, noncoding RNAs, and proteins associated with various features of PTMC progression. Some studies propose that peripheral and tumor tissue-infiltrating immune cells could serve as biomarkers for the clinical progression of PTMC. Collectively, these clinical and molecular features offer a rationale for the early detection and the development of precision theranostic strategies of clinically progressive PTMC. [ABSTRACT FROM AUTHOR]

Abstract As one of the most prevalent digestive system tumours, colorectal cancer (CRC) poses a significant threat to global human health. With the emergence of immunotherapy and target therapy, the prognosis for the majority of CRC patients has notably improved. However, the subset of patients with BRAF exon 15 p.V600E mutation (BRAFV600E) has not experienced remarkable benefits from these therapeutic advancements. Hence, researchers have undertaken foundational investigations into the molecular pathology of this specific subtype and clinical effectiveness of diverse therapeutic drug combinations. This review comprehensively summarised the distinctive molecular features and recent clinical research advancements in BRAF‐mutant CRC. To explore potential therapeutic targets, this article conducted a systematic review of ongoing clinical trials involving patients with BRAFV600E‐mutant CRC.

Abstract Objective This study aimed to investigate the clinicopathological features and prognostic indicators of alveolar soft part sarcoma (ASPS). Methods The characteristics of 26 ASPS patients diagnosed at our hospital between January 2011 and January 2019 were retrospectively analysed. Results The data for 12 male and 14 female patients, with a median age of 27.5 years, were assessed. The clinical symptoms mainly included painless enlarged masses in deep soft tissues. ASPS had a characteristic pathological morphology. Twenty-four patients were positive for TFE3, and TFE3 gene rearrangement was detected in 12 patients. Among the 26 patients who completed follow-up, 14 had metastasis, 1 had local recurrence, and 7 died. Kaplan–Meier survival analysis revealed that prognosis was significantly correlated with sex, tumour size and metastasis (P

The serrated pathway to colorectal cancers (CRCs) is a significant pathway encompassing five distinct types of lesions, namely hyperplastic polyps (HPs), sessile serrated lesions (SSLs), sessile serrated lesions with dysplasia (SSL-Ds), traditional serrated adenomas (TSAs), and serrated adenoma unclassified. In contrast to the conventional adenoma-carcinoma pathway, the serrated pathway primarily involves two mechanisms: BRAF/KRAS mutations and CpG island methylator phenotype (CIMP). HPs are the most prevalent non-malignant lesions, while SSLs play a crucial role as precursors to CRCs, On the other hand, traditional serrated adenomas (TSAs) are the least frequently encountered subtype, also serving as precursors to CRCs. It is crucial to differentiate these lesions based on their unique morphological characteristics observed in histology and colonoscopy, as the identification and management of these serrated lesions significantly impact colorectal cancer screening programs. The management of these lesions necessitates the crucial steps of removing premalignant lesions and implementing regular surveillance. This article provides a comprehensive summary of the epidemiology, histologic features, molecular features, and detection methods for various serrated polyps, along with recommendations for their management and surveillance. [ABSTRACT FROM AUTHOR]

Background: Lung cancer is the most prevalent cancer diagnosis and the leading cause of cancer death worldwide. Therapeutic failure in lung cancer (LUAD) is heavily influenced by drug resistance. This challenge stems from the diverse cell populations within the tumor, each having unique genetic, epigenetic, and phenotypic profiles. Such variations lead to varied therapeutic responses, thereby contributing to tumor relapse and disease progression. Methods: The Genomics of Drug Sensitivity in Cancer (GDSC) database was used in this investigation to obtain the mRNA expression dataset, genomic mutation profile, and drug sensitivity information of NSCLS. Machine Learning (ML) methods, including Random Forest (RF), Artificial Neurol Network (ANN), and Support Vector Machine (SVM), were used to predict the response status of each compound based on the mRNA and mutation characteristics determined using statistical methods. The most suitable method for each drug was proposed by comparing the prediction accuracy of different ML methods, and the selected mRNA and mutation characteristics were identified as molecular features for the drug-responsive cancer subtype. Finally, the prognostic influence of molecular features on the mutational subtype of LUAD in publicly available datasets. Results: Our analyses yielded 1,564 gene features and 45 mutational features for 46 drugs. Applying the ML approach to predict the drug response for each medication revealed an upstanding performance for SVM in predicting Afuresertib drug response (area under the curve [AUC] 0.875) using CIT, GAS2L3, STAG3L3, ATP2B4-mut, and IL15RA-mut as molecular features. Furthermore, the ANN algorithm using 9 mRNA characteristics demonstrated the highest prediction performance (AUC 0.780) in Gefitinib with CCL23-mut. Conclusion: This work extensively investigated the mRNA and mutation signatures associated with drug response in LUAD using a machine-learning approach and proposed a priority algorithm to predict drug response for different drugs. [ABSTRACT FROM AUTHOR]

By presenting a comprehensive analysis of low-grade serous carcinomas (LGSCs), a subset of epithelial ovarian cancers, this review delves into their distinct molecular characteristics, clinicopathological features and systemic therapy options, emphasizing their differences from high-grade serous carcinomas (HGSCs). Notably, LGSCs exhibit prevalent RAS/RAF/MEK/MAPK pathway activation, KRAS and BRAF mutations, and infrequent p53 mutations. While chemotherapy is commonly employed, LGSCs display lower responsiveness compared to HGSCs. Hormone therapy, particularly endocrine maintenance therapy, is explored due to the higher estrogen receptor expression. Novel therapeutic approaches involving CDK4/6 inhibitors, MEK inhibitors, and antiangiogenic agents like bevacizumab are also investigated. Ongoing clinical trials are striving to enhance LGSC treatment strategies, offering valuable insights for future therapeutic advancements in this challenging ovarian cancer subtype.

Alternansucrase (ASR), classified in GH70, produces unique α-glucans with alternating α-1,3 and α-1,6 glycosidic linkages in the backbone chain from renewable sucrose which is easily obtained from nature with low cost. ASR has synthesized many products with valuable functionalities that hold enormous commercial interest and promising applications. The influence of biocatalysis and fermentation parameters on the yields, and properties of products are critical for the propositions made to promote the enzyme application. Investigations on ASR have been compiled in the review to provide information on the enzyme, products and parameters. This review summarizes studies on the characteristics, conversion mechanism, products, and beneficial applications of ASR and exhibits structure-based technologies to improve enzyme activity, specificity, and thermostability for industrial applications. Finally, prospects for further development are also proposed for various ASR applications in food and other fields. • Systematically elaborate the origin, biocatalysis, and current application status of alternansucrases for its applications in foods. • The limitations in practical applications of alternansucrase are explained in depth. • Thorough overview of strategies for engineering or remodeling alternausucrase for industrial application. • Future perspectives were proposed to cope with the challenges of design and applications of the alternausucrase. [ABSTRACT FROM AUTHOR]

Soil-derived dissolved organic matter (DOM) links soil and water carbon pools and is an important source of photochemically produced reactive intermediates (PPRIs) in aquatic environments. Despite its importance, the variations in photochemical reactivity of soil-derived DOM molecules in producing PPRIs across broad geographical regions, and the factors driving these variations, remain unclear. Herein, we resolved the apparent quantum yields (Φ(PPRIs)) of hydroxyl radicals (•OH), singlet oxygen ( 1 O 2 ), and excited triplet-state DOM ( 3 DOM*) for irradiated DOM from 22 representative soil reference materials in China, and linked them to soil pH, mineral weathering degree, and DOM characteristics. Generally, the average Φ(PPRIs) values of the soil-derived DOM followed the order of Φ( 3 DOM*) (1.67× 10 -2 ) > Φ( 1 O 2 ) (1.47× 10 -2 ) > Φ(•OH) (7.31× 10 -5 ). The DOM from less weathered soils showed higher Φ(•OH) and Φ( 3 DOM*) and comparable Φ( 1 O 2 ) than that from more weathered soils. The differences were mainly regulated by the abundance of humic-, lignin-, tannin-, and aromatic-like compounds, as indicated by the correlation and random forest model analyses. Partial least squares and multiple linear regression analyses identified DOM molecular weight, nominal oxidation state of carbon, and soil chemical index of alteration as effective predictors of •OH yields. Soil chemical index of alteration emerged as a prioritized predictor of 3 DOM* yields, while the electron-donating capacity and humic-like compound content of the soil-derived DOM were effective predictors of 1 O 2 yields. This study advances our understanding of how mineral weathering processes regulate the photochemical reactivity of soil-derived DOM in the aquatic environment across wide geographical regions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

As one of the most prevalent digestive system tumours, colorectal cancer (CRC) poses a significant threat to global human health. With the emergence of immunotherapy and target therapy, the prognosis for the majority of CRC patients has notably improved. However, the subset of patients with BRAF exon 15 p.V600E mutation (BRAF V600E ) has not experienced remarkable benefits from these therapeutic advancements. Hence, researchers have undertaken foundational investigations into the molecular pathology of this specific subtype and clinical effectiveness of diverse therapeutic drug combinations. This review comprehensively summarised the distinctive molecular features and recent clinical research advancements in BRAF-mutant CRC. To explore potential therapeutic targets, this article conducted a systematic review of ongoing clinical trials involving patients with BRAF V600E -mutant CRC., (© 2024 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Background: Brain tumours are known to have a high mortality and morbidity rate due to their localised and frequent invasive growth. The concept that glioma resistance could originate from the dissimilarity in the vulnerability of clonogenic glial stem cells to chemotherapeutic drugs and radiation has driven the scientific community to reexamine the comprehension of glioma growth and strategies that target these cells or modify their stemness., Methods: Based on the enrichment scores of 12 stemness signatures, we identified glioma subtypes in both tumour bulks and single cells by clustering analysis. Furthermore, we comprehensively compared molecular and clinical features among the glioma subtypes., Results: Consistently, in seven different datasets, hierarchical clustering uncovered three subtypes of glioma, termed Stem-H, Stem-M, and Stem-L, with high, medium, and low stemness signatures, respectively. Stem-H and Stem-L exhibited the most unfavorable and favourable overall and disease-free survival, respectively. Stem-H showed the highest enrichment scores of the EMT, invasion, proliferation, differentiation, and metastasis processes signatures, while Stem-L displayed the lowest. Stem-H harboured a greater proportion of late-stage tumours compared to Stem-L. Moreover, Stem-H manifested higher tumour mutation burden, DNA damage repair and cell cycle activity, intratumour heterogeneity, and a more frequent incidence of TP53 and EGFR mutations than Stem-L. In contrast, Stem-L had higher O6-Methylguanine-DNA Methyltransferase (MGMT) methylation levels., Conclusion: The classification of glioma based on stemness may offer new insights into the biology of the tumour, as well as more accurate clinical management of the disease., Competing Interests: Declaration of competing interest All authors declare that there is no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

By presenting a comprehensive analysis of low-grade serous carcinomas (LGSCs), a subset of epithelial ovarian cancers, this review delves into their distinct molecular characteristics, clinicopathological features and systemic therapy options, emphasizing their differences from high-grade serous carcinomas (HGSCs). Notably, LGSCs exhibit prevalent RAS/RAF/MEK/MAPK pathway activation, KRAS and BRAF mutations, and infrequent p53 mutations. While chemotherapy is commonly employed, LGSCs display lower responsiveness compared to HGSCs. Hormone therapy, particularly endocrine maintenance therapy, is explored due to the higher estrogen receptor expression. Novel therapeutic approaches involving CDK4/6 inhibitors, MEK inhibitors, and antiangiogenic agents like bevacizumab are also investigated. Ongoing clinical trials are striving to enhance LGSC treatment strategies, offering valuable insights for future therapeutic advancements in this challenging ovarian cancer subtype., Competing Interests: GG, JS, GO, AS, LB, and AM were employed by company Oncoclínicas&Co – Medica Scientia Innovation Research (MEDSIR). The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Giannecchini, da Silva, de Oliveira Bretas, dos Santos, Baltar and de Melo.)

Objective: Mammographic calcifications are a common feature of breast cancer, but their molecular characteristics and treatment implications in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer remain unclear., Methods: We retrospectively collected mammography records of an HR+/HER2- breast cancer cohort ( n = 316) with matched clinicopathological, genomic, transcriptomic, and metabolomic data. On the basis of mammographic images, we grouped tumors by calcification status into calcification-negative tumors, tumors with probably benign calcifications, tumors with calcification of low-moderate suspicion for maligancy and tumors with calcification of high suspicion for maligancy. We then explored the molecular characteristics associated with each calcification status across multiple dimensions., Results: Among the different statuses, tumors with probably benign calcifications exhibited elevated hormone receptor immunohistochemical staining scores, estrogen receptor (ER) pathway activation, lipid metabolism, and sensitivity to endocrine therapy. Tumors with calcifications of high suspicion for malignancy had relatively larger tumor sizes, elevated lymph node metastasis incidence, Ki-67 staining scores, genomic instability, cell cycle pathway activation, and may benefit from cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors., Conclusions: Our research established links between tumor calcifications and molecular features, thus proposing potential precision treatment strategies for HR+/HER2- breast cancer., Competing Interests: No potential conflicts of interest are disclosed., (Copyright: © 2024, The Authors.)

Clear cell papillary renal cell tumour (CCPRCT) is a kind of renal epithelial cell tumor, and was renamed by the 5th WHO due to its specific epidemiology and clinicopathological characteristics. However, the biological mechanism and molecular basis of CCPRCT still need to be further clarified. This study aims to comprehensively evaluate clinicopathologic and molecular characteristics of CCPRCC, and particularly compare it with other more prevalent subtypes of renal cell carcinoma. 12 cases of CCPRCT were collected for analyzing the clinicopathological characteristics. Then, whole-exome sequencing (WES) was employed to reveal the genetic profiles, followed by comparison with the molecular genetic alterations identified in ccRCC (341) and pRCC (200) datasets obtained from the TCGA database. Of the 12 CCPRCT cases, the male-to-female ratio was 4:1 with a mean age of 49.5 years (48.5 ± 10.5) at diagnosis. All patients were diagnosed accidentally during routine physical examinations. All tumors (12/12, 100%）had a solid-cystic appearance with a well-defined fibrous capsule. The median size of the tumors was 3 cm (2.98 ± 1.2). Histologically, the cystic papillary structures were considered to be prominent, lined with cuboidal tumor cells away from basement membrane. The tumor cells were moderately atypia equivalent to grade 1 or grade 2 according to the ISUP nuclear grading system. Typically, the tumor cell diffusely positive for CK7 and CAIX in a "cup-like" pattern. The results of WES revealed recurrent gene alterations (mainly missense mutation) of TTN and FLT in 4 cases (4/12, 33.3%), respectively, of which, the alteration of FLT was not observed in ccRCC and pRCC of the TCGA database. Other gene alterations including POTEC (1 cases), PRADC1 (1 cases) , ZZZ3 (1 case) and PTPRZ1 (1 case), etc. Moreover, all of the CCPRCT cases displayed a lower tumor mutation burden (TMB) compared to ccRCC and pRCC with median TMB of 1.04 (range: 1.94 ± 2.74). None of the patients experienced tumor metastasis, recurrence, or tumor-related deaths. CCPRCT is a renal epithelial cell tumor characterized by specific clinical and pathological features. Our study provides additional evidence supporting the favorable prognosis of CCPRCT. Furthermore, the potential molecular alterations were uncovered by this study in CCPRCT such as the FLT family and TTN. However, due to the limited sample size, larger studies are required to validate these findings. [ABSTRACT FROM AUTHOR]

Arabinoxylan (AX) is well-known for its emulsification and beneficial biological activity, but the roles of AX's molecular features and interfacial properties in AX-based emulsion behaviors were unknown. We first used a multi-scale approach to correlate molecular, interfacial, droplet characteristics, and bulk emulsion of AXs from corn and wheat bran (CAXs and WAXs). Our results showed that among CAXs and WAXs solution (1 %, 2 % and 3 %, w / v), 0.25 M NaOH-treated CAX and WAX showed smaller particle sizes (493 nm and 8621 nm), lower interfacial tension and stronger interfacial layer, whose emulsion exhibited smaller initial droplets (541 nm and 660 nm) and better stability. Moreover, WAXs had bigger particle sizes, lower interfacial tension and stronger interfacial layer than CAXs, but CAXs exhibited better emulsifying and emulsion-stabilizing properties than WAXs. There is a satisfactory correlation among CAXs' or WAXs' molecular features, interfacial properties and emulsion behaviors. However, a good correlation from different grains AXs cannot be established. [Display omitted] • AXs' cereal origin and NaOH concentrations could greatly influenced their particle size and interfacial properties. • CAXs had better emulsifying capacities and emulsion stability than WAXs. • AXs with 0.25 M NaOH exhibited better emulsifying capacity and emulsion stability. • There was a satisfactory correlation among CAXs' or WAXs' particle size, interfacial and emulsion properties. [ABSTRACT FROM AUTHOR]

The serrated pathway to colorectal cancers (CRCs) is a significant pathway encompassing five distinct types of lesions, namely hyperplastic polyps (HPs), sessile serrated lesions (SSLs), sessile serrated lesions with dysplasia (SSL-Ds), traditional serrated adenomas (TSAs), and serrated adenoma unclassified. In contrast to the conventional adenoma-carcinoma pathway, the serrated pathway primarily involves two mechanisms: BRAF/KRAS mutations and CpG island methylator phenotype (CIMP). HPs are the most prevalent non-malignant lesions, while SSLs play a crucial role as precursors to CRCs, On the other hand, traditional serrated adenomas (TSAs) are the least frequently encountered subtype, also serving as precursors to CRCs. It is crucial to differentiate these lesions based on their unique morphological characteristics observed in histology and colonoscopy, as the identification and management of these serrated lesions significantly impact colorectal cancer screening programs. The management of these lesions necessitates the crucial steps of removing premalignant lesions and implementing regular surveillance. This article provides a comprehensive summary of the epidemiology, histologic features, molecular features, and detection methods for various serrated polyps, along with recommendations for their management and surveillance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Xu, Hu, Li, Yao, Han, Zhang and Qu.)