OBJECTIVE: To explore the clinical significance of circulating tumor DNA (ctDNA) in response evaluation and relapse monitoring for patients with primary mediastinal large B-cell lymphoma (PMBCL). METHODS: The clinical characteristics, efficacy and survival of 38 PMBCL patients in our hospital from January 2010 to April 2020 were retrospectively analyzed. The ctDNA monitoring was conducted by targeted next-generation sequencing (NGS). RESULTS: Among the 38 patients, 26 cases were female, and 32 cases were diagnosed with Ann Arbor stage I-II. The 5-year overall survival (OS) rate and progression-free survival (PFS) rate were 74.7% and 61.7%, respectively. Males and those with high aaIPI scores (3 points) had a relatively poor prognosis. The NGS results of 23 patients showed that STAT6 (65.2%), SOCS1 (56.5%), and TNFAIP3 (56.5%) were the most common mutated genes. Patients with stable disease (SD)/progressive disease (PD) exhibited enrichment in cell cycle, FoxO, and TNF signaling pathways. A total of 29 patients underwent end-of-treatment PET/CT (EOT PET/CT), and 16 of them received ctDNA monitoring with 12 negative. Among 6 patients with EOT PET/CT positive (Deauville 4), 4 underwent ctDNA monitoring, and 3 of them were negative, being still in continuous remission without any subsequent anti-tumor therapy. CONCLUSION CtDNA may be combined with PET/CT to assess efficacy, monitor relapse, and guide treatment of PMBCL.
Humans ; Circulating Tumor DNA/blood* ; Female ; Mediastinal Neoplasms ; Male ; Retrospective Studies ; High-Throughput Nucleotide Sequencing ; Prognosis ; Lymphoma, Large B-Cell, Diffuse/genetics* ; Middle Aged ; Adult ; Aged ; Neoplasm Recurrence, Local ; Mutation

OBJECTIVE: To investigate the correlation of the potential functional microRNA (miRNA)-mRNA regulatory network with recurrence of high-grade serous ovarian carcinoma (HGSOC) and its biological significance. METHODS: This study was performed based on the data of 354 patients with HGSOC from the Cancer Genome Atlas database. In these patients, HGSOC was divided into different subtypes based on the pathways identified by GO analysis, and the correlations of the subtypes with HGSOC recurrence and differentially expressed miRNAs and mRNAs were assessed. Two relapse-related datasets were identified using the Gene Set Enrichment (GSE) database, from which the differentially expressed miRNAs were identified by intersection with the TCGA data. The target genes of these miRNAs were predicted using miRWalk 2.0 database, and these common differentially expressed miRNAs and mRNAs were used to construct the key miRNA-mRNA network associated with HGSOC recurrence. The expression of miR-506-3p and SNAI2 in two ovarian cancer cell lines was detected using RT-qPCR and Western blotting, and their targeted binding was verified using a double luciferase assay. The effect of miR-506-3p expression modulation on ovarian cancer cell migration was detected using scratch assay and Transwell assay. RESULTS: We screened 303 GO terms of HGSOC-related pathways and identified two HGSOC subtypes (C1 and C2). The subtype C1 was associated with a significantly higher recurrence rate than C2. The differentially expressed genes between C1 and C2 subtypes were mainly enriched in epithelial-mesenchymal transition (EMT). Five miRNAs were identified as potential regulators of EMT, and a total of 41 target genes were found to be involved in the differential expressions of EMT pathway between C1 and C2 subtypes. The key miRNA-mRNA network associated with HGSOC recurrence was constructed based on these 5 miRNAs and 41 mRNAs. MiR-506-3p was confirmed to bind to SNAI2, and up-regulation of miR-506-3p significantly inhibited SNAI2 expression and reduced migration and invasion of SKOV3 and CAOV3 cells (P < 0.05), while miR-506-3p knockdown produced the opposite effects (P < 0.05). CONCLUSION MiR-506-3p and SNAI2 are the key molecules associated with HGSOC recurrence. MiR-506-3p may affect EMT of ovarian cancer cells by regulating cell migration and invasion via SNAI2, and its expression level has predictive value for HGSOC recurrence.
Humans ; Female ; MicroRNAs/genetics* ; Neoplasm Recurrence, Local/genetics* ; Ovarian Neoplasms/genetics* ; Computational Biology

We explored clinicopathological features and treatment strategies for thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT). Thoracic SMARCA4-UT is a new entity recently acknowledged in the 2021 edition of World Health Organization Classification of Thoracic Tumors, and doctors are relatively unfamiliar with its diagnosis, treatment, and prognosis. Taking a case of SMARCA4-UT treated in Peking University First Hospital as an example, this multi-disciplinary discussion covered several hot issues on diagnosing and treating thoracic SMARCA4-UT, including histological features, immu- nohistochemical and molecular phenotype, immune checkpoint inhibitor (ICI) therapy, and pathological assessment of neoadjuvant therapy response. The patient was an older man with a long history of smoking and was admitted due to a rapidly progressing solid tumor in the lower lobe of the right lung. Histologically, tumor cells were epithelioid, undifferentiated, diffusely positive for CD34, and partially positive for SALL4.The expression of BRG1 protein encoded by SMARCA4 gene was lost in all of tumor cells, and next-generation sequencing(NGS)confirmed SMARCA4 gene mutation (c.2196T>G, p.Y732Ter). The pathological diagnosis reached as thoracic SMARCA4-UT, and the preoperative TNM stage was T1N2M0 (ⅢA). Tumor proportion score (TPS) detected by immunohistochemistry of programmed cell death 1-ligand 1 (PD-L1, clone SP263) was 2%. Tumor mutation burden (TMB) detected by NGS of 1 021 genes was 16. 3/Mb. Microsatellite detection showed the tumor was microsatellite stable (MSS). Neo-adjuvant therapy was implemented with the combined regimen of chemotherapy and ICI. Right lower lobectomy was performed through thoracoscopy after the two weeks' neoadjuvant. The pathologic assessment of lung tumor specimens after neoadjuvant therapy revealed a complete pathological response (CPR). The post-neoadjuvant tumor TNM stage was ypT0N0M0. Then, five cycles of adjuvant therapy were completed. Until October 2022, neither tumor recurrence nor metastasis was detected, and minimal residual disease (MRD) detection was negative. At present, it is believed that if BRG1 immunohistochemical staining is negative, regardless of whether SMARCA4 gene mutation is detected, it should be classified as SMARCA4-deficient tumors. SMARCA4-deficient tumors include a variety of carcinomas and sarcomas. The essential criteria for diagnosing SMARCA4-UT includes loss of BRG1 expression, speci-fic histological morphology, and exclude other common thoracic malignant tumors with SMARCA4-deficiency, such as squamous cell carcinoma, adenocarcinoma and large cell carcinoma. SMARCA4-UT is a very aggressive malignant tumor with a poor prognosis. It has almost no targeted therapy mutations, and little response to chemotherapy, but ICI is currently the only effective drug. The successful diagnosis and treatment for this case of SMARCA4-UT should enlighten significance for various kinds of SMARCA4-deficient tumors.
Humans ; Immune Checkpoint Inhibitors ; Neoplasm Recurrence, Local ; Lung Neoplasms/genetics* ; Thoracic Neoplasms/pathology* ; Adenocarcinoma ; DNA Helicases ; Nuclear Proteins ; Transcription Factors

BACKGROUND: Breast cancer patients who are positive for hormone receptor typically exhibit a favorable prognosis. It is controversial whether chemotherapy is necessary for them after surgery. Our study aimed to establish a multigene model to predict the relapse of hormone receptor-positive early-stage Chinese breast cancer after surgery and direct individualized application of chemotherapy in breast cancer patients after surgery. METHODS: In this study, differentially expressed genes (DEGs) were identified between relapse and nonrelapse breast cancer groups based on RNA sequencing. Gene set enrichment analysis (GSEA) was performed to identify potential relapse-relevant pathways. CIBERSORT and Microenvironment Cell Populations-counter algorithms were used to analyze immune infiltration. The least absolute shrinkage and selection operator (LASSO) regression, log-rank tests, and multiple Cox regression were performed to identify prognostic signatures. A predictive model was developed and validated based on Kaplan-Meier analysis, receiver operating characteristic curve (ROC). RESULTS: A total of 234 out of 487 patients were enrolled in this study, and 1588 DEGs were identified between the relapse and nonrelapse groups. GSEA results showed that immune-related pathways were enriched in the nonrelapse group, whereas cell cycle- and metabolism-relevant pathways were enriched in the relapse group. A predictive model was developed using three genes ( CKMT1B , SMR3B , and OR11M1P ) generated from the LASSO regression. The model stratified breast cancer patients into high- and low-risk subgroups with significantly different prognostic statuses, and our model was independent of other clinical factors. Time-dependent ROC showed high predictive performance of the model. CONCLUSIONS A multigene model was established from RNA-sequencing data to direct risk classification and predict relapse of hormone receptor-positive breast cancer in Chinese patients. Utilization of the model could provide individualized evaluation of chemotherapy after surgery for breast cancer patients.
Humans ; Female ; Breast Neoplasms/genetics* ; East Asian People ; Neoplasm Recurrence, Local/genetics* ; Breast ; Algorithms ; Chronic Disease ; Prognosis ; Tumor Microenvironment

Circulating tumor DNA (ctDNA) is emerging as a novel biomarker for tumor evaluation, offering advantages such as high sensitivity and specificity, minimal invasiveness, and absence of radiation. Currently, various techniques including gene sequencing and PCR are employed for ctDNA detection. The utilization of ctDNA for monitoring minimal residual disease (MRD) enables comprehensive assessment of tumor status and early identification of tumor recurrence, achieving a remarkable detection sensitivity of 0.01%. Therefore, ctDNA holds promise as a biomarker for early diagnosis, treatment response monitoring, and prognosis prediction in solid tumors. This article reviews the commonly used methods for detecting ctDNA and their advantages in evaluating tumor MRD and guiding clinical diagnosis and treatment.
Humans ; Circulating Tumor DNA/genetics* ; Neoplasm, Residual/genetics* ; Biomarkers, Tumor/genetics* ; Neoplasm Recurrence, Local ; Prognosis

OBJECTIVES: Glioma is the most common malignant tumor in the central nervous system, and the hypoxic microenvironment is prevalent in solid tumors. This study aims to investigate the up-regulation of genes under the condition of hypoxia and their roles in glioma growth, as well as their impact on glioma prognosis. METHODS: The hypoxia-related dataset with glioma was screened in the Gene Expression Omnibus database (GEO), and the differentially expressed genes were analyzed between hypoxia and normoxia through bioinformatics, and chromosome 10 open reading frame 10 (C10orf10) was verified and screened in hypoxia-treated cells through real-time PCR and Western blotting. The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) datasets were downloaded to analyze the mRNA expression of C10orf10 in different grades of glioma and its impact on prognosis. The glioma specimens and follow-up data of 68 gliomas who underwent surgical treatment in Xiangya Hospital of Central South University from March 2017 to January 2021 were collected, and real-time PCR was used to detect the mRNA expression of C10orf10 in different grades of glioma, and the Kaplan-Meier method was used to analyze the relationship between the expression C10orf10 and prognosis. The glioma cells, which could interfere the expression of C10orf10, were constructed, and the effect of C10orf10 on the proliferation of glioma cells was evaluated by cell counting kit-8 (CCK-8) and colony formation assays. RESULTS: Compared with the condition of normoxia, the expression levels of C10orf10 mRNA and protein were significantly up-regulated in glioma cells under hypoxia (P<0.001), and the mRNA expression level of C10orf10 in glioma tissues was up-regulated with the increase of WHO grade in glioma (P<0.001). Based on Kaplan-Meier survival analysis, the higher the mRNA expression level of C10orf10 was, the shorter the survival time of the patient was (P<0.05). And the expression of C10orf10 mRNA was higher in recurrent gliomas than that in primary gliomas in the CGGA database (P<0.001). Knockdown of C10orf10 could significantly inhibit the growth of glioma cells both under hypoxia and normoxia (both P<0.001). CONCLUSIONS The expression level of C10orf10 can promote the proliferation and prognosis of glioma, which is expected to become a prognostic marker and therapeutic target for glioma.
Humans ; Central Nervous System ; Glioma/genetics* ; Hypoxia ; Neoplasm Recurrence, Local ; Prognosis ; Tumor Microenvironment

With the concept of "Precision Medicine" in malignant tumors popularized, many substances carrying valuable clinical information have emerged in the process of exploring the occurrence and development of tumors from a microscopic perspective. Circulating tumor DNA (ctDNA) is one of them. In various clinical stages of cancer, ctDNA exhibits rich diagnostic values including demonstrating the efficacy of treatment, predicting prognosis, and monitoring disease recurrence. This article mainly describes the application and research progress of ctDNA in different stages of clinical diagnosis and treatment of non-small cell lung cancer .
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Biomarkers, Tumor/genetics* ; Carcinoma, Non-Small-Cell Lung/genetics* ; Circulating Tumor DNA/genetics* ; Humans ; Lung Neoplasms/genetics* ; Mutation ; Neoplasm Recurrence, Local

Significant progress has been made in lung cancer screening, surgery, chemoradiation, targeted therapy, and immunotherapy recently. Surgical resection is the most important treatment for localized non-small cell lung cancer (NSCLC) so far, but there are still many patients who develop local recurrence or distant metastases within 5 years of surgery. Currently, the risk factors of recurrence in patients with NSCLC are mainly based on clinical and pathological features, which hardly identify patients at high risk of recurrence accurately. With the development of new detection technologies, a number of molecular markers that may have a predictive risk of recurrence in NSCLC have been discovered over the years. In order to summarize the molecular markers related to postoperative recurrence in NSCLC patients, we have formulated a consensus on the prediction of postoperative recurrence of NSCLC based on molecular markers. This consensus mainly focuses on the early stage NSCLC patients, discusses and summarizes the risk factors of disease recurrence from the molecular level. It is hoped that more and more valuable information can be provided for the management of patients, so as to provide more guidance for the perioperative management of the patients with early stage NSCLC in the future.
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Humans ; Carcinoma, Non-Small-Cell Lung/surgery* ; Lung Neoplasms/surgery* ; Consensus ; Early Detection of Cancer ; Neoplasm Staging ; Neoplasm Recurrence, Local/genetics*

Objective: To investigate the clinical and pathological features of salivary secretory carcinoma (SSC). Methods: Ten cases of SSC confirmed in the Department of Pathology,Capital Medical University School of Stomatology from January 2014 to December 2021 were retrospectively included, including 5 males and 5 females, with a median age of 46.5 years. The microscopic morphology, immunophenotype, special staining and clinical follow-up of 10 cases of salivary secretory carcinoma were observed. Ten patients were tested with S-100, vimentin, mammaglobin, Dog-1, p63 and Ki-67, 9 cases with cytokeratin (CK) 8/18, 8 with CK7, 6 with calponin, 5 with smooth muscle actin (SMA) and GCDFP15, 4 with CK5/6 and 1 with SOX10. The ETV6-NTRK3 fusion gene was detected by fluorescence in situ hybridization. Results: Seven of the 10 SSC were located in the parotid gland and 3 were located in the cheeks. Histomorphology showed solid, papillary-cystic, follicular, microcystic, and macrocystic types. In 7 cases, tumor cells were dominated by single arrangement type, while certain mixed arrangements existed in some areas. The cytoplasm of the tumor cells was rich in eosinophilic, fine granular or vacuolar shapes, and clear cytoplasm was seen in 2 cases. The nuclei were mostly oval-shaped vesicular nuclei, with nucleoli in the center. Immunohistochemistry showed CK7 (8/8) positive, CK8/18 (9/9) positive, S-100 (10/10) positive, vimentin (5/10) positive, (4/10) partially positive and (1/10) less partially positive, mammaglobin (7/10) positive, (1/10) partially positive and (2/10) some individual cells positive, Dog-1 (10/10) negative, CK5/6 (4/4) negative, p63 (7/10) negative and (3/10) partially positive, SMA (5/5) negative, calponin (6/6) negative, and Ki-67 index was 5%-20%. Secretions of 5 cases showed periodic acid-Schiff (PAS) and PAS with diastase (PAS-D) staining positive. All 10 cases showed ETV6-NTRK3 fusion positive. Six cases were successfully followed up for 32-91 months, of which 2 cases recurred after 28 and 74 months and underwent surgical resection again. All cases followed up are alive and disease-free. Conclusions: The salivary secretory carcinoma is a rare low-grade malignant tumor. In certain cases, morphology is atypical and mammaglobin is immunohistochemically positive in only individual tumor cells. Therefore, the diagnosis should be supported with morphology, immunohistochemical staining, and molecular feature preferably.
Female ; Male ; Biomarkers, Tumor ; Carcinoma/pathology* ; In Situ Hybridization, Fluorescence ; Ki-67 Antigen/genetics* ; Neoplasm Recurrence, Local ; Retrospective Studies ; S100 Proteins ; Salivary Gland Neoplasms/pathology* ; Vimentin

Preoperative neoadjuvant chemoradiotherapy, combined with total mesorectal excision, has become the standard treatment for advanced localized rectal cancer (RC). However, the biological complexity and heterogeneity of tumors may contribute to cancer recurrence and metastasis in patients with radiotherapy-resistant RC. The identification of factors leading to radioresistance and markers of radiosensitivity is critical to identify responsive patients and improve radiotherapy outcomes. MicroRNAs (miRNAs) are small, endogenous, and noncoding RNAs that affect various cellular and molecular targets. miRNAs have been shown to play important roles in multiple biological processes associated with RC. In this review, we summarized the signaling pathways of miRNAs, including apoptosis, autophagy, the cell cycle, DNA damage repair, proliferation, and metastasis during radiotherapy in patients with RC. Also, we evaluated the potential role of miRNAs as radiotherapeutic biomarkers for RC.
Humans ; MicroRNAs/metabolism* ; Neoplasm Recurrence, Local ; Rectal Neoplasms/pathology* ; Neoadjuvant Therapy ; Radiation Tolerance/genetics*