Objective To explore the clinical and immunological significance of CCDC97 in hepatocellular carcinoma (HCC). Methods Clinical data and RNA sequencing results from HCC patients were retrieved from TCGA and ICGC databases. Bioinformatics analysis and in vitro experiments were performed to investigate the role of CCDC97 in HCC. Results The expression level of CCDC97 was elevated in HCC patients and HCC cells, closely associated with pathological features and prognosis. CCDC97 was identified as a novel prognostic biomarker. It is linked to the spliceosome pathway, which is significantly active in tumors and potentially promotes carcinogenesis. CCDC97 is also highly expressed in various immune cells and is associated with microenvironment. Furthermore, knocking down CCDC97 in vitro suppressed cell migration, invasion, and proliferation. Conclusion CCDC97 plays a critical role in HCC progression and the immune microenvironment, making it a potential target for prognosis and therapeutic intervention.

Non-small cell lung cancer, characterized by high incidence and mortality rates, significantly threatens human health. Precisely assessing patient prognosis and implementing adaptive treatment strategies have emerged as pivotal issues in contemporary thoracic oncology. Postoperative minimal residual disease (MRD) detection through liquid biopsy has demonstrated substantial potential. Circulating tumor DNA (ctDNA) enables real-time dynamic monitoring of tumor alterations. With advancements in ctDNA detection technologies, ctDNA has become a core method for MRD assessment. In the context of postoperative surveillance, ctDNA detection facilitates more accurate prognostic stratification and early prediction of tumor recurrence. Regarding therapeutic interventions, ctDNA detection can predict the efficacy of neoadjuvant and adjuvant therapies. In the future, further elucidating the value of assessing ctDNA status in predicting patient prognosis and guiding drug therapies will contribute to the advancement of precision medicine and adaptive treatments.

OTU domain-containing protein 3 (OTUD3) is a crucial deubiquitinase that exhibits significant expression differences across various disease models. OTUD3 plays a role in regulating biological functions such as apoptosis, inflammatory responses, cell cycle, proliferation, and invasion in different cell types. By deubiquitinating key substrate proteins, OTUD3 is involved in essential physiological and pathological processes, including innate antiviral immunity, neural development, neurodegenerative diseases, and cancer. OTUD3 exhibits tumor-suppressive effects in breast cancer, esophageal cancer, colon cancer, and papillary thyroid cancer, but acts as an oncogenic in liver and lung cancers. OTUD3 serves as a biomarker in predicting diagnosing, and assessing prognosis for certain malignancies. Despite its potential, the molecular mechanisms of OTUD3 in many diseases are still not well-understood, and exploring OTUD3's regulatory mechanisms is essential for comprehending its roles in immunity and disease. Future research will focus on developing OTUD3-targeted therapies.

The genomic fusions of the anaplastic lymphoma kinase (ALK) gene have been widely recognized as effective therapeutic targets for non-small cell lung carcinoma (NSCLC). The Second Xiangya Hospital of Central South University has treated 2 NSCLC patients with 2 distinct novel ALK gene fusions. Case 1 was a 55-year-old male with a solid nodule located in the right hilar lobe on enhanced CT scan. Case 2 was a 47-year-old female with enhanced CT showing involvement of the left upper lobe of lung. Histopathological examination of tumor tissues confirmed lung adenocarcinoma in both cases. Immunohistochemical (IHC) staining demonstrated positivity for thyroid transcription factor-1 (TTF-1) and ALK-D5F3 in tumor cells, while negativity for P40. The next-generation sequencing (NGS) tests identified a PNPT1-ALK (Exon22:Exon20) fusion variant in case 1 and a TCEAL2-ALK (Exon3:Exon19) fusion variant in case 2. The TCEAL2-ALK fusion was further confirmed by amplification refractory mutation system (ARMS)-PCR at the mRNA level. Both patients were treated with oral alectinib at a dosage of 600 mg twice daily. The tumors in both patients were significantly decreased after alectinib treatment, achieving partial response. At the time of submission, there was an absence of disease progression and the progression-free survival (PFS) had surpassed 1 year. It offered compelling evidences that the individuals with NSCLC and harboring either a PNPT1-ALK (Exon22:Exon20) fusion or a TCEAL2-ALK (Exon3:Exon19) fusion, experience favorable therapeutic outcomes through the administration of alectinib. This study expands the known ALK fusion variants database and supports the precision treatment of NSCLC using ALK tyrosine kinase inhibitors (TKIs).

Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer subtype with poor prognosis. RNA alternative splicing dysregulation plays a critical role in the initiation and progression of TNBC. This article systematically introduces the basic process of RNA splicing and then focuses on reviewing the aberrant alternative splicing events and their biological effects in TNBC: 1) Multiple splicing-related factors promote tumor cell proliferation and mediate chemotherapy resistance by regulating the alternative splicing of genes involved in cell survival and drug response; 2) dysregulation of splicing regulatory networks leads to altered splicing of multiple metastasis-related genes, promoting tumor invasion and metastasis; 3) aberrant alternative splicing events participate in tumor progression by affecting the expression of DNA damage repair genes; 4) dysregulation of alternative splicing is also involved in the regulation of tumor immune evasion and stem cell properties. A deeper understanding of the mechanisms underlying RNA alternative splicing dysregulation in TNBC is essential for elucidating its molecular pathology, identifying novel prognostic markers, and developing therapeutic strategies.

Monitoring minimal residual disease (MRD) and timely intervention are effective strategies for preventing relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adult acute myeloid leukemia (AML). The WT1 gene, a pan-leukemia marker, can be used as an indicator for MRD monitoring in AML patients. Currently, there is no unified standard for the intervention timing or treatment threshold based on WT1 gene detection after transplantation. This study aims to evaluate the clinical value of WT1 gene-guided preemptive therapy and further explore its optimal intervention threshold.

Long non-coding RNAs (lncRNAs) play an essential role in cancer biology. Cervical intraepithelial neoplasia grade 3 (CIN3) is the most severe precancerous lesion of cervical cancer. However, the mechanism of multiple lncRNAs in CIN3 has not been studied in-depth and is worth exploring. This study aims to summarize the lncRNA expression profile in CIN 3 and screen for lncRNAs with potential oncogenic effects.

The objective of the present study was to investigate the role and mechanism of bone marrow microenvironmental cells in regulating the mitochondrial mass of leukemia cells, and to uncover the mechanism of leukemia progression at the metabolic level. A mouse model of acute myeloid leukemia (AML) induced by the overexpression of the MLL-AF9 (MA9) fusion protein was established, and the bone marrow cells of AML mice were transplanted into mitochondrial fluorescence reporter mice expressing the Dendra2 protein (mito-Dendra2 mice). The proportion of Dendra2+ cells in bone marrow leukemia cells at different stages of AML was quantified by flow cytometry. The effects of transferred mitochondria on leukemia cells were studied by fluorescence-activated cell sorting (FACS), followed by functional experiments and bulk RNA sequencing. Finally, components within the bone marrow niche, such as mesenchymal stromal cells (MSCs) and endothelial cells (ECs), were co-cultured with leukemia cells in vitro. The proportion of leukemia cells that underwent mitochondrial transfer and the apoptosis level of leukemia cells were then detected by flow cytometry. The results showed that mitochondria from bone marrow cells were transferred to leukemia cells in the AML mouse model, and the proportion of mitochondrial transfer decreased with AML progression. The proportion of mitochondria transferred to leukemia stem cells (LSCs) was lower than that of mature AML cells. In AML cells receiving Dendra2+ mitochondria, there was a significant increase in the levels of intracellular reactive oxygen species (ROS) and apoptosis, while the levels of protein translation and their colony-forming capacities were decreased. The transplantation of Dendra2+ AML cells resulted in an extension of the survival of mice. RNA sequencing analysis demonstrated a significant downregulation of pathways related to translation, aerobic respiration and mitochondrial organization in AML cells that had received mitochondria. In vitro co-culture experiments indicated that MSCs within the bone marrow niche tended to transfer their mitochondria to leukemia cells and promoted the apoptosis of leukemia cells. These results indicate that in the MA9-induced AML mouse model, bone marrow niche cells can transfer mitochondria to leukemia cells, resulting in a reduction in the overall survival and function of the leukemia cells. Mitochondrial transfer in the bone marrow microenvironment may serve as a self-defensive mechanism of the host bone marrow niche cells, inhibiting the progression of AML.

Minimal residual disease (MRD), a crucial biomarker for assessing efficacy and predicting recurrence, refers to residual tumor cells remaining in the body of patients with hematological malignancies who achieved complete remission after treatment. This study aimed to conduct a retrospective analysis of the clinical diagnosis, treatment, and MRD monitoring of a pediatric patient with multiple acute B-lymphocytic leukemia relapses, alongside a review of relevant literature. In this case, Ig rearrangement based on next-generation sequencing (NGS) was more accurate in assessing the MRD level, compared with the traditional method of MRD detection, indicating the risk of earlier relapse and guided interventions in time. Additionally, NGS-MRD detected clonal evolution, providing new ideas to further investigate the intrinsic factors of disease development.

This case report presents a patient with pediatric acute myeloid leukemia (AML) with RUNX1∷MTG16, admitted to the Blood Disease Hospital of the Chinese Academy of Medical Sciences in October 2023. He was 13 years old, with a chief complaint of fatigue for 20 days. Bone marrow smear revealed 17.0% blasts, the karyotype was 46,XY,t (16; 21) (q24; q22), molecular biology demonstrated RUNX1∷MTG16 fusion gene, combined with FLT3-ITD mutation. The child was diagnosed with AML (with RUNX1 ∷ MTG16). Complete remission was achieved after chemotherapy induction. The induction therapy regimen was mitoxantrone hydrochloride liposomes combined with cytarabine (MA). The RUNX1 ∷ MTG16 and FLT3-ITD were negative after another MA treatment course. However, the RUNX1 ∷ MTG16 and FLT3-ITD were turning positive during the following intensive treatment, and he then successfully underwent matched sibling donor umbilical cord blood transplantation.

This study aimed to assess the efficacy and safety of gilteritinib combined with chemotherapy in treating newly diagnosed FLT3-mutated acute myeloid leukemia (AML). We retrospectively collected clinical data from 16 patients newly diagnosed with FLT3-mutated AML at Jiangsu Province Hospital. Patients received induction therapy with the classic "3 + 7" regimen or the VA regimen, and all patients were immediately supplied with gilteritinib after detecting FLT3-ITD/TKD mutations. Of the 16 patients, 12 were male and 4 were female, with a median age of 52.5 years (range: 15-76 years). Additionally, 15 patients had FLT3-ITD mutations and 1 had FLT3-TKD mutation. The complete remission (CR/CRi) rate was 93.8% (15/16) after the first cycle of gilteritinib-based induction therapy, with 13 patients achieving MRD negativity detected with flow cytometry. All patients achieved a CR(MRD-) during the consolidation phase. FLT3 mutation clearance was achieved among all 14 patients who underwent next-generation sequencing (NGS) analysis. The 12-month overall survival and relapse-free survival rates were both 73.9%, respectively, with a median followup of 18 months. Nine (56.2%) patients experienced infectious fever during the induction therapy. Three patients had grade 3 QTc prolongation during consolidation and maintenance therapy. Treatment-related adverse events were generally tolerable.

Brain metastasis has emerged as a significant challenge in the comprehensive management of patients with non-small cell lung cancer (NSCLC), particularly in those harboring driver gene mutations. Traditional treatments such as radiotherapy and surgery offer limited clinical benefits and are often accompanied by cognitive dysfunction and a decline in quality of life. In recent years, novel small molecule tyrosine kinase inhibitors targeting epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and other pathways have been developed, effectively penetrating the blood-brain barrier while enhancing intracranial drug concentrations and improving patient outcomes. This advancement has transformed the treatment landscape for brain metastases in NSCLC. Consequently, the Lung Cancer Medical Education Committee of the Chinese Medical Education Association and the Brain Metastasis Collaboration Group of the Lung Cancer Youth Expert Committee of the Beijing Medical Reward Foundation have jointly initiated and formulated the Clinical Practice Guidelines for the Management of Brain Metastases from Non-small Cell Lung Cancer with Actionable Gene Alterations in China (2025 Edition). This guideline integrates the latest research findings with clinical experience, adhering to multidisciplinary treatment principles, and encompasses aspects such as diagnosis, timing of intervention, and systemic and local treatment options for driver gene positive NSCLC brain metastases. Additionally, it proposes individualized treatment strategies tailored to different driver gene types, aiming to provide clinicians with a reference to enhance the overall diagnostic and therapeutic standards for NSCLC brain metastases in China.
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Objective: To investigate the clinicopathological and molecular genetic characteristics of intracranial mesenchymal tumors with FET::CREB fusion transcript. Methods: The clinical and imaging data of 6 cases of intracranial mesenchymal tumors with FET::CREB fusion from December 2018 to December 2023 were collected at the First Affiliated Hospital of Zhengzhou University. Their histological features, immunophenotype and molecular characteristics were analyzed. Results: Among the 6 patients, 4 were males and 2 were females, and the median age was 20 years. The clinical symptoms were increased intracranial pressure in 5 cases and epilepsy in 1 case. The lesion sites were cerebellum (2 cases), frontal lobe (2 cases), parietal lobe (1 case), and cranioorbital communication (1 case). The radiological features mainly showed solid or cystic components, with obvious annular enhancement on MRI. The histopathological features showed a wide spectrum of morphology, clear boundaries and fibrous pseudocapsule. The tumor cells were arranged in a lamellar or nodular pattern, and some in cord or loose network. The tumor cells were spindle, oval, epithelioid or stellate. The stroma was collagenous or mucin-rich, and accompanied by abundant lymphocytes and plasma cells infiltration. By immunohistochemical staining, desmin, CD99 and EMA were expressed in 6 cases, CD68 in 1 case, MUC4 in 1 case, synaptophysin in 2 cases, and ALK in 1 case. The Ki-67 proliferation index was between 1%-15%. Molecular analysis showed EWSR1::ATF1 fusion in 3 cases, EWSR1::CREB1 fusion in 2 cases, and EWSR1::CREM fusion in 1 case. Conclusions: Intracranial mesenchymal tumors with FET::CREB fusion are relatively rare and typically occur in children and younger adults. These tumors have a broad morphological spectrum and often express desmin, CD99 and EMA. The molecular characteristics are the gene fusions of FET family (mainly EWSR1, FUS) with CREB family transcription factors (ATF1, CREB1 or CREM). It is necessary to distinguish these tumors from meningiomas and solitary fibrous tumors, and the combination of immunohistochemical staining and molecular genetic testing can effectively help identify these tumors.

Objective: To investigate the characteristics of RET gene rearrangement revealed by fluorescence in situ hybridization (FISH) in lung cancer. Methods: A total of 616 formalin-fixed paraffin-embedded surgical samples from lung adenocarcinomas with wild-type EGFR gene and no ALK protein expression by immunohistochemistry obtained at Peking Union Medical College Hospital, Beijing, China between December 2019 and April 2022 were included. Thirty-three tumors with RET gene rearrangement determined by imbalanced-based reverse-transcription droplet digital PCR (RT-ddPCR) were analyzed using break-apart FISH. The results were confirmed, and RET gene fusion variants were identified through next generation sequencing (NGS). Results: RET gene rearrangements were found in all 33 RET RT-ddPCR positive cases via NGS, including 27 cases of KIF5B::RET, 3 CCDC6::RET, 2 ERC1::RET and 1 CCDC186::RET rearrangements. Moreover, 32 RET positive and 1 RET negative cases were defined using FISH. Among the RET FISH-positive cases, 25 (78.1%, 25/32) showed break-apart FISH signal pattern in 52%-100% of tumor cells with the rearrangement and 7 cases (21.9%, 7/32) presented isolated 3' signal type in 38%-88% positive tumor cells. There was no RET-positive case with single 5' pattern in the cohort. The most common partner gene was KIF5B (81.8%, 27/33). Most of the patients with RET gene rearrangement were female (72.7%, 24/33). Conclusion: RET FISH-positive lung cancer is commonly characterized by a high proportion of rearrangement cancer cells and break-apart FISH signal type.

Objective: To understand the clinicopathological and molecular genetic characteristics of aggressive renal mucinous tubular and spindle cell carcinoma (MTSCC). Methods: The clinical features, histology, immunophenotype, molecular characteristics and prognosis of 4 cases of metastatic/recurrent renal MTSCC that were submitted to the Peking University Third Hospital (2 cases), Institute of Urology, Peking University (one case) and Zhejiang Provincial People's Hospital (one case) from 2015 to 2020 were retrospectively reviewed and analyzed. Results: Among the four patients, two were male and two were female. The average age was 58 years, ranging from 28 to 77 years. Three patients underwent radical nephrectomy, while one underwent partial nephrectomy. The tumor size was 2-8 cm (mean, 5.6 cm). There were two cases classified as pT3a, one case as pT1b and one case as pT1a. Histologically, the tumors were mainly composed of tubules and spindle cell cords. For nuclear grade, three cases were G3 and one case was G2. Extracellular mucus was present in all four cases. Sarcomatoid features and tumor necrosis were observed in one and three cases, respectively. Immunohistochemistry showed that PAX8 (4/4), AMACR (4/4), CK7 (4/4), CKpan (3/3), vimentin (3/3) and CK8/18 (2/2) were positive in the tumor cells, but CAⅨ (1/4) or CD10 (2/3) were focally positive or negative. Fluorescence in situ hybridization showed that no trisomy of chromosomes 7 and l7 (2/2). Targeted next generation sequencing were performed in all four cases and showed that 3 cases had mutations in Hippo pathway involving MET (2/4), NF2 (1/4) and NTRK1 (1/4) genes. The other potentially pathogenic mutations involved KDM6A, SETD2 and PALB2. The follow-up period was 13 to 99 months. The time between diagnosis and metastasis/recurrence ranged from 6 to 58 months. Two patients died after lung metastasis occurred, one had multi-organ and multi-site lymph node metastases, and one achieved disease-free survival after resection of metastatic/recurrent foci. Conclusions: Renal MTSCC is a rare and distinct entity. The presence of high nuclear grade and pathological stage, high-grade morphology, lymphovascular invasion, and tumor necrosis suggests potential aggressive behaviors. It is thus recommended to report these histological features and conduct active follow-up and surveillance after surgery. The frequent mutations in MET, NF2 and NTRK1 suggest that dysregulation of Hippo pathway may be related to the development and progression of renal MTSCC.

Objective: To investigate the clinicopathological characteristics, immunophenotypes, diagnostic criteria and differential diagnosis of atrophic kidney-like lesion (AKLL). Methods: Three cases of AKLL were collected from April 2021 to October 2023 at the Xiangya Hospital of Central South University, Changsha, Zhejiang Provincial People's Hospital, Hangzhou and Ningbo Clinical Pathology Diagnosis Center, Ningbo, China. The clinical, morphological, and immunohistochemical characteristics were analyzed. Relevant literature was also reviewed. A targeted DNA-based next-generation sequencing (a panel of 150 genes) was performed on one of the three cases. Results: There were 1 female and 2 males, aged 30, 57, and 17 years (mean 34.6 years), respectively. The lesions were all incidentally identified during physical or imaging examination. Radiologically, they were all presented as a unilateral renal parenchymal mass. Grossly, the maximum diameters of the lesions were 1.8, 4.0, and 6.5 cm (mean 4.1 cm), respectively. The tumor cut-surfaces were sponge-like, multilocular cystic, and solid, respectively. At low magnification, the lesions were well-circumscribed, while a thick fibromuscular capsule was noted in cases 1 and 3. Cases 1 and 2 were composed of thin-walled cysts or follicular like structures of varying sizes, with the cyst wall lined by flattened and atrophic, or hobnail cells. The luminal spaces contained dense eosinophilic secretion and associated calcifications, while some cysts contained discohesive cells floating in the eosinophilic material. The tissue between the cysts showed predominantly small atrophic tubular structures. Case 3 was almost entirely composed of atrophic and collapsed tubular structures with focal cyst formation, imparting a solid sheets growth pattern under low magnification. Immunohistochemical staining revealed that the cyst lining cells and the intracystic floating cells were WT1 positive, PAX8 negative and CK7 negative, while the atrophic renal tubules were WT negative, PAX8 positive and CK7 positive. Targeted next-generation sequencing in case 1 showed no significant genetic abnormalities. All 3 patients underwent partial nephrectomy. No evidence of recurrence or metastasis was found with a follow-up of 17 to 36 months. Conclusions: AKLL is a rare and novel benign renal disease. It is easily misdiagnosed as a renal neoplasm grossly and histologically. Careful morphological observation combined with characteristic immunophenotypes can aid in its diagnosis and differential diagnosis.