Development of a cell adhesion-based prognostic model for multiple myeloma: Insights into chemotherapy response and potential reversal of adhesion effects.

Multiple myeloma (MM) is a hematologic malignancy notorious for its high relapse rate and development of drug resistance, in which cell adhesion-mediated drug resistance plays a critical role. This study integrated four RNA sequencing datasets (CoMMpass, GSE136337, GSE9782, and GSE2658) and focused on analyzing 1706 adhesion-related genes. Rigorous univariate Cox regression analysis identified 18 key prognosis-related genes, including KIF14, TROAP, FLNA, MSN, LGALS1, PECAM1, and ALCAM, which demonstrated the strongest associations with poor overall survival (OS) in MM patients. To comprehensively evaluate the impact of cell adhesion on MM prognosis, an adhesion-related risk score (ARRS) model was constructed using Lasso Cox regression analysis. The ARRS model emerged as an independent prognostic factor for predicting OS. Furthermore, our findings revealed that a heightened cell adhesion effect correlated with tumor resistance to DNA-damaging drugs, protein kinase inhibitors, and drugs targeting the PI3K/Akt/mTOR signaling pathway. Nevertheless, we identified promising drug candidates, such as tirofiban, pirenzepine, erlotinib, and bosutinib, which exhibit potential in reversing this resistance. In vitro, experiments employing NCIH929, RPMI8226, and AMO1 cell lines confirmed that MM cell lines with high ARRS exhibited poor sensitivity to the aforementioned candidate drugs. By employing siRNA-mediated knockdown of the key ARRS model gene KIF14, we observed suppressed proliferation of NCIH929 cells, along with decreased adhesion to BMSCs and fibronectin. This study presents compelling evidence establishing cell adhesion as a significant prognostic factor in MM. Additionally, potential molecular mechanisms underlying adhesion-related resistance are proposed, along with viable strategies to overcome such resistance. These findings provide a solid scientific foundation for facilitating clinically stratified treatment of MM.

Clinical implications of single cell sequencing for bladder cancer.

Bladder cancer (BC) is the 10th most common cancer worldwide, with about 0.5 million reported new cases and about 0.2 million deaths per year. In this scoping review, we summarize the current evidence regarding the clinical implications of single-cell sequencing for bladder cancer based on PRISMA guidelines. We searched PubMed, CENTRAL, Embase, and supplemented with manual searches through the Scopus, and Web of Science for published studies until February 2023. We included original studies that used at least one single-cell technology to study bladder cancer. Forty-one publications were included in the review. Twenty-nine studies showed that this technology can identify cell subtypes in the tumor microenvironment that may predict prognosis or response to immune checkpoint inhibition therapy. Two studies were able to diagnose BC by identifying neoplastic cells through single-cell sequencing urine samples. The remaining studies were mainly a preclinical exploration of tumor microenvironment at single cell level. Single-cell sequencing technology can discriminate heterogeneity in bladder tumor cells and determine the key molecular properties that can lead to the discovery of novel perspectives on cancer management. This nascent tool can advance the early diagnosis, prognosis judgment, and targeted therapy of bladder cancer.

GRIK1 promotes glioblastoma malignancy and is a novel prognostic factor of poor prognosis.

Primary tumors of the central nervous system (CNS) are classified into over 100 different histological types. The most common type of glioma is derived from astrocytes, and the most invasive glioblastoma (WHO IV) accounts for over 57% of these tumors. Glioblastoma (GBM) is the most common and fatal tumor of the CNS, with strong growth and invasion capabilities, which makes complete surgical resection almost impossible. Despite various treatment methods such as surgery, radiotherapy, and chemotherapy, glioma is still an incurable disease, and the median survival time of patients with GBM is shorter than 15 months. Thus, molecular mechanisms of GBM characteristic invasive growth need to be clarified to improve the poor prognosis. Glutamate ionotropic receptor kainate type subunit 1 (GRIK1) is essential for brain function and is involved in many mental and neurological diseases. However, GRIK1's pathogenic roles and mechanisms in GBM are still unknown. Single-nuclear RNA sequencing of primary and recurrent GBM samples revealed that GRIK1 expression was noticeably higher in the recurrent samples. Moreover, immunohistochemical staining of an array of GBM samples showed that high levels of GRIK1 correlated with poor prognosis of GBM, consistent with The Cancer Genome Atlas database. Knockdown of GRIK1 retarded GBM cells growth, migration, and invasion. Taken together, these findings show that GRIK1 is a unique and important component in the development of GBM and may be considered as a biomarker for the diagnosis and therapy in individuals with GBM.

Developing risk models and subtypes of autophagy-associated LncRNAs for enhanced prognostic prediction and precision in therapeutic approaches for liver cancer patients.

Background: Limited research has been conducted on the influence of autophagy-associated long non-coding RNAs (ARLncRNAs) on the prognosis of hepatocellular carcinoma (HCC). Methods: We analyzed 371 HCC samples from TCGA, identifying expression networks of ARLncRNAs using autophagy-related genes. Screening for prognostically relevant ARLncRNAs involved univariate Cox regression, Lasso regression, and multivariate Cox regression. A Nomogram was further employed to assess the reliability of Riskscore, calculated from the signatures of screened ARLncRNAs, in predicting outcomes. Additionally, we compared drug sensitivities in patient groups with differing risk levels and investigated potential biological pathways through enrichment analysis, using consensus clustering to identify subgroups related to ARLncRNAs. Results: The screening process identified 27 ARLncRNAs, with 13 being associated with HCC prognosis. Consequently, a set of signatures comprising 8 ARLncRNAs was successfully constructed as independent prognostic factors for HCC. Patients in the high-risk group showed very poor prognoses in most clinical categories. The Riskscore was closely related to immune cell scores, such as macrophages, and the DEGs between different groups were implicated in metabolism, cell cycle, and mitotic processes. Notably, high-risk group patients demonstrated a significantly lower IC50 for Paclitaxel, suggesting that Paclitaxel could be an ideal treatment for those at elevated risk for HCC. We further identified C2 as the Paclitaxel subtype, where patients exhibited higher Riskscores, reduced survival rates, and more severe clinical progression. Conclusion: The 8 signatures based on ARLncRNAs present novel targets for prognostic prediction in HCC. The drug candidate Paclitaxel may effectively treat HCC by impacting ARLncRNAs expression. With the identification of ARLncRNAs-related isoforms, these results provide valuable insights for clinical exploration of autophagy mechanisms in HCC pathogenesis and offer potential avenues for precision medicine.

IQGAP3 promotes the progression of glioma as an immune and prognostic marker.

Background: IQGAP3 plays a crucial role in regulating cell proliferation, division, and cytoskeletal organization. Abnormal expression of IQGAP3 has been linked to various tumors, but its function in glioma is not well understood. Methods: Various methods, including genetic differential analysis, single-cell analysis, ROC curve analysis, Cox regression, Kaplan-Meier analysis, and enrichment analysis, were employed to analyze the expression patterns, diagnostic potential, prognostic implications, and biological processes involving IQGAP3 in normal and tumor tissues. The impact of IQGAP3 on immune infiltration and the immune microenvironment in gliomas was evaluated using immunofluorescence. Additionally, the cBioPortal database was used to analyze copy number variations and mutation sites of IQGAP3. Experimental validation was also performed to assess the effects of IQGAP3 on glioma cells and explore underlying mechanisms. Results: High IQGAP3 expression in gliomas is associated with an unfavorable prognosis, particularly in wild-type IDH and 1p/19q non-codeleted gliomas. Enrichment analysis revealed that IQGAP3 is involved in regulating the cell cycle, PI3K/AKT signaling, p53 signaling, and PLK1-related pathways. Furthermore, IQGAP3 expression may be closely related to the immunosuppressive microenvironment of glioblastoma. BRD-K88742110 and LY-303511 are potential drugs for targeting IQGAP3 in anti-glioma therapy. In vitro experiments showed that downregulation of IQGAP3 inhibits the proliferation and migration of glioma cells, with the PLK1/PI3K/AKT pathway potentially playing a crucial role in IQGAP3-mediated glioma progression. Conclusion: IQGAP3 shows promise as a valuable biomarker for diagnosis, prognosis, and immunotherapeutic strategies in gliomas.

Investigation of the feasibility of NRAV as a biomarker for hepatocellular carcinoma.

The long non-coding RNA, Negative Regulator of Antiviral Response (NRAV) has been identified as a participant in both respiratory virus replication and immune checkpoints, however, its involvement in pan-cancer immune regulation and prognosis, particularly those of hepatocellular carcinoma (HCC), remains unclear. To address this knowledge gap, we analyzed expression profiles obtained from The Cancer Genome Atlas (TCGA) database, comparing normal and malignant tumor tissues. We found that NRAV expression is significantly upregulated in tumor tissues compared to adjacent nontumor tissues. Kaplan-Meier (K-M) analysis revealed the prognostic power of NRAV, wherein overexpression was significantly linked to reduced overall survival in a diverse range of tumor patients. Furthermore, noteworthy associations were observed between NRAV, immune checkpoints, immune cell infiltration, genes related to autophagy, epithelial-mesenchymal transition (EMT), pyroptosis, tumor mutational burden (TMB), and microsatellite instability (MSI) across different cancer types, including HCC. Moreover, NRAV upregulation expression was associated with multiple pathological stages by clinical observations. Furthermore, our investigation revealed a substantial elevation in the expression of NRAV in both HCC tumor tissues and cells compared to normal tissues and cells. The inhibition of NRAV resulted in the inhibition of cell proliferation, migration, and invasion in HCC cells, while also influencing the expression of CD274 (PD-L1) and CD44, along with various biomarkers associated with EMT, autophagy, and pyroptosis. The aforementioned results propose NRAV as a promising prognostic biomarker for HCC.

Identifying and validating MMP family members (MMP2, MMP9, MMP12, and MMP16) as therapeutic targets and biomarkers in kidney renal clear cell carcinoma (KIRC).

Kidney Renal Clear Cell Carcinoma (KIRC) is a malignant tumor that carries a substantial risk of morbidity and mortality. The MMP family assumes a crucial role in tumor invasion and metastasis. This study aimed to uncover the mechanistic relevance of the MMP gene family as a therapeutic target and diagnostic biomarker in Kidney Renal Clear Cell Carcinoma (KIRC) through a comprehensive approach encompassing both computational and molecular analyses. STRING, Cytoscape, UALCAN, GEPIA, OncoDB, HPA, cBioPortal, GSEA, TIMER, ENCORI, DrugBank, targeted bisulfite sequencing (bisulfite-seq), conventional PCR, Sanger sequencing, and RT-qPCR based analyses were used in the present study to analyze MMP gene family members to accurately determine a few hub genes that can be utilized as both therapeutic targets and diagnostic biomarkers for KIRC. By performing STRING and Cytohubba analyses of the 24 MMP gene family members, MMP2 (matrix metallopeptidase 2), MMP9 (matrix metallopeptidase 9), MMP12 (matrix metallopeptidase 12), and MMP16 (matrix metallopeptidase 16) genes were denoted as hub genes having highest degree scores. After analyzing MMP2, MMP9, MMP12, and MMP16 via various TCGA databases and RT-qPCR technique across clinical samples and KIRC cell lines, interestingly, all these hub genes were found significantly overexpressed at mRNA and protein levels in KIRC samples relative to controls. The notable effect of the up-regulated MMP2, MMP9, MMP12, and MMP16 was also documented on the overall survival (OS) of the KIRC patients. Moreover, targeted bisulfite-sequencing (bisulfite-seq) analysis revealed that promoter hypomethylation pattern was associated with up-regulation of hub genes (MMP2, MMP9, MMP12, and MMP16). In addition to this, hub genes were involved in various diverse oncogenic pathways. The MMP gene family members (MMP2, MMP9, MMP12, and MMP16) may serve as therapeutic targets and prognostic biomarkers in KIRC.

Degradation of FAK-targeting by proteolytic targeting chimera technology to inhibit the metastasis of hepatocellular carcinoma.

Liver cancer is a prevalent malignant cancer, ranking third in terms of mortality rate. Metastasis and recurrence primarily contribute to the high mortality rate of liver cancer. Hepatocellular carcinoma (HCC) has low expression of focal adhesion kinase (FAK), which increases the risk of metastasis and recurrence. Nevertheless, the efficacy of FAK phosphorylation inhibitors is currently limited. Thus, investigating the mechanisms by which FAK affects HCC metastasis to develop targeted therapies for FAK may present a novel strategy to inhibit HCC metastasis. This study examined the correlation between FAK expression and the prognosis of HCC. Additionally, we explored the impact of FAK degradation on HCC metastasis through wound healing experiments, transwell invasion experiments, and a xenograft tumor model. The expression of proteins related to epithelial-mesenchymal transition (EMT) was measured to elucidate the underlying mechanisms. The results showed that FAK PROTAC can degrade FAK, inhibit the migration and invasion of HCC cells in vitro, and notably decrease the lung metastasis of HCC in vivo. Increased expression of E-cadherin and decreased expression of vimentin indicated that EMT was inhibited. Consequently, degradation of FAK through FAK PROTAC effectively suppressed liver cancer metastasis, holding significant clinical implications for treating liver cancer and developing innovative anti-neoplastic drugs.

Prognostic Value of Complete Resection of the High-Frequency Oscillation Area in Intracranial EEG: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: High-frequency oscillations (HFOs; ripples 80-250 Hz; fast ripples [FRs] 250-500 Hz) recorded with intracranial electrodes generated excitement and debate about their potential to localize epileptogenic foci. We performed a systematic review and meta-analysis on the prognostic value of complete resection of the HFOs-area (crHFOs-area) for epilepsy surgical outcome in intracranial EEG (iEEG) accessing multiple subgroups. METHODS: We searched PubMed, Embase, and Web of Science for original research from inception to October 27, 2022. We defined favorable surgical outcome (FSO) as Engel class I, International League Against Epilepsy class 1, or seizure-free status. The prognostic value of crHFOs-area for FSO was assessed by (1) the pooled FSO proportion after crHFOs-area; (2) FSO for crHFOs-area vs without crHFOs-area; and (3) the predictive performance. We defined high combined prognostic value as FSO proportion >80% + FSO crHFOs-area >without crHFOs-area + area under the curve (AUC) >0.75 and examined this for the clinical subgroups (study design, age, diagnostic type, HFOs-identification method, HFOs-rate thresholding, and iEEG state). Temporal lobe epilepsy (TLE) was compared with extra-TLE through dichotomous variable analysis. Individual patient analysis was performed for sex, affected hemisphere, MRI findings, surgery location, and pathology. RESULTS: Of 1,387 studies screened, 31 studies (703 patients) met our eligibility criteria. Twenty-seven studies (602 patients) analyzed FRs and 20 studies (424 patients) ripples. Pooled FSO proportion after crHFOs-area was 81% (95% CI 76%-86%) for FRs and 82% (73%-89%) for ripples. Patients with crHFOs-area achieved more often FSO than those without crHFOs-area (FRs odds ratio [OR] 6.38, 4.03-10.09, p < 0.001; ripples 4.04, 2.32-7.04, p < 0.001). The pooled AUCs were 0.81 (0.77-0.84) for FRs and 0.76 (0.72-0.79) for ripples. Combined prognostic value was high in 10 subgroups: retrospective, children, long-term iEEG, threshold (FRs and ripples) and automated detection and interictal (FRs). FSO after complete resection of FRs-area (crFRs-area) was achieved less often in people with TLE than extra-TLE (OR 0.37, 0.15-0.89, p = 0.006). Individual patient analyses showed that crFRs-area was seen more in patients with FSO with than without MRI lesions (p = 0.02 after multiple correction). DISCUSSION: Complete resection of the brain area with HFOs is associated with good postsurgical outcome. Its prognostic value holds, especially for FRs, for various subgroups. The use of HFOs for extra-TLE patients requires further evidence.

Predicting Stage Progression in Binet Stage a Chronic Lymphocytic Leukemia.

INTRODUCTION: The variable clinical course of chronic lymphocytic leukemia (CLL) and the lack of consensus on follow-up and treatment strategies have necessitated a prognostic model for identifying high-risk patients at the time of diagnosis. METHODS: We involved a retrospective analysis of demographic and clinical characteristics of 212 patients diagnosed with Binet stage A CLL and thus eligible for risk stratification by both the International Prognostic Score for Early-stage CLL (IPS-E) and the alternative IPS-E (AIPS-E). We evaluated the applicability of these prognostic indices in our young, Middle Eastern cohort (median age 59 at diagnosis). RESULTS: During the study period with a median follow-up of 3.5 years, 67 patients (32 %) experienced progression to first treatment and cumulative incidence of treatment was 13 % at 1 year and 28 % at 3 years after diagnosis. Sixty-nine (51 % of the 136 with a known value) patients harbored an unmutated immunoglobulin heavy chain gene (IGHV) and 21 (10 %) an 11q or 17p deletion with 11 % lacking FISH results. For each early-stage CLL prognostic index, more patients were identified as high-risk for disease progression (51 % of 124 patients evaluable for IPS-E; 42 % of 109 patients evaluable for AIPS-E) than intermediate-risk and low-risk. Multivariable models involving the IPS-E and AIPS-E components revealed that unmutated IGHV and elevated absolute lymphocyte count were significant predictors of earlier treatment requirement. Both prognostic scores were discriminative of time to first treatment (log-rank p < 0.001; c-statistics of 0.74 for IPS-E and 0.69 for AIPS-E). CONCLUSION: Although clarity on clinical behavior with regard to initiation of treatment remains elusive, IPS-E and AIPS-E are valuable tools for identifying high-risk patients.

[Clinical characteristics and prognosis of primary aldosteronism associated with subclinical Cushing syndrome].

Objective: To analyze the clinical characteristics and prognosis of patients with primary aldosteronism (PA) associated with subclinical Cushing syndrome (SCS). Methods: This retrospective cohort study was conducted at the First Affiliated Hospital of Chongqing Medical University in China. Patients with PA were included between January 2014 and December 2022. According to the results of 1-mg overnight dexamethasone suppression test, the patients were divided into the PA group and PA associated with SCS (PA/SCS) group. The demographic information, hormone levels, and follow-up results were analyzed. Independent sample t-test, chi-square test and Mann-Whitney U test were used for data comparison. Results: A total of 489 PA patients were enrolled in this study, of which 109 had PA/SCS (22.3%). Patients with SCS were on average older (54.4±10.7 vs. 47.4±11.0, P<0.001); had a larger proportion of women (69.7%, 76/109 vs. 57.4%, 218/380; P=0.020); and a longer duration of hypertension [96 (36, 180) vs. 60 (12, 120) months, P=0.001] than patients without SCS. There were 215 and 51 patients in the PA group and PA/SCS group, who completed adrenalectomy and follow-up, respectively. The remission rate of autonomous cortisol secretion in the PA/SCS group was 85.3% (29/34). There was no significant difference in the remission rate of autonomous aldosterone secretion among patients between the PA/SCS and PA group (94.1%, 48/51 vs. 94.4%, 203/215; P=1.000), while the clinical remission rate in the PA/SCS group was lower than that in the PA group (39.2%, 20/51 vs. 61.9%, 133/215; P=0.003). Conclusions: SCS is common in PA patients (22.3%), and the clinical remission rate is low. Screening using the 1-mg overnight dexamethasone suppression test is recommended for all patients with PA.

Identifying Predictors of Mortality in Sepsis Patients with Malignancy: A Retrospective Cohort Study.

BACKGROUND: Sepsis is a major problem that contributes to a high mortality rate. Its mortality is especially high in patients with malignancy. One study reported that sepsis patients with malignancy have a 2.32 times higher risk of mortality compared to patients without malignancy. For this reason, factors that influence mortality in sepsis patients with malignancy become especially important to provide effective and efficient therapy. This study aims to identify factors that influence mortality in sepsis patients with malignancy. METHODS: This study is a retrospective cohort study using medical records of sepsis patients with malignancy who were treated at Cipto Mangunkusumo Hospital from 2020 to 2022. A bivariate analysis was carried out and followed by a logistic regression analysis on variables with p-value<0.25 on the bivariate analysis. RESULTS: Among the 350 eligible sepsis subjects with malignancy, there was an 82% mortality rate (287 subjects). Bivariate and multivariate analyses revealed significant associations between mortality and both SOFA score (adjusted Odds Ratio of 5.833, 95%CI 3.214-10.587) and ECOG performance status (adjusted Odds Ratio of 3.490, 95%CI 1.690-7.208). CONCLUSION: SOFA score and ECOG performance status are significantly associated with sepsis patient mortality in malignancy cases.

[The research of the contralateral ear hearing thresholds and the hearing prognosis in unilateral Meniere's disease].

Objective:This study analyzed the pure tone audiometry results of the affected ear and the contralateral ear of unilateral Meniere's disease to investigate the correlation of the hearing threshold of the contralateral ear and the hearing prognosis of unilateral Meniere's disease. Methods:In this study, the follow-up data of 135 patients with unilateral Meniere's disease in Beijing Tongren Hospital were used to analyze the pure tone audiometry results of the affected and contralateral ears at the first visit and 1 year later. Results:①At the first visit, there was no statistically significant difference between the mean hearing thresholds of the affected ear in the normal hearing group and the high-frequency hearing loss group of the contralateral ear（P>0.05）. ②The range of improvement of hearing thresholds in the affected ear was greater in the contralateral ear normal hearing group than in the contralateral ear high-frequency hearing loss group. In the normal hearing group of the contralateral ear, the hearing thresholds of the affected ear at 0.25 kHz（P<0.01）, 0.50 kHz（P<0.01）, 1.00 kHz（P<0.01）, and 2.00 kHz（P<0.05） were significantly improved; and in the high-frequency hearing loss group of the contralateral ear, the hearing thresholds at 0.25 kHz（P<0.01） hearing thresholds improved significantly, and there was no significant difference between the rest of the frequencies before and after treatment（P>0.05）. A consistent pattern was observed in both higher and lower age groups. ③After 1 year of follow-up, the low and mid-frequency hearing of the affected ear improved. 0.25 kHz（P<0.01）, 0.50 kHz（P<0.01）, 1.00 kHz（P<0.01） hearing thresholds improved significantly; 8.00 kHz hearing thresholds decreased slightly（P<0.05）. Conclusion:After standardized treatment, the results of 1-year follow-up suggested that the low-frequency hearing of MD patients could be improved, but the high-frequency hearing was slightly decreased. The hearing prognosis of the affected ear with normal hearing threshold of the contralateral ear may be better.

[Clinicopathological characteristics and immune microenvironment of breast squamous cell carcinoma].

Objective: To investigate the clinicopathological characteristics of breast squamous cell carcinoma and to analyze the relationship between its immune microenvironment tumor infiltrating lymphocytes (TILs) and prognosis. Methods: Forty-four cases of primary squamous cell carcinoma of the breast diagnosed and treated in the First Affiliated Hospital of Air Force Medical University, Xi'an, China from January 2006 to July 2022 were selected. Their clinicopathological characteristics were analyzed. The cell composition of TILs was evaluated using immunohistochemistry (Mainly markers of B lymphocytes, T lymphocytes and plasma cells). The relationship between TILs and prognosis was also analyzed. Results: The 44 patients of breast squamous cell carcinoma were all female and all were invasive carcinoma. Eight cases (8/44, 18.2%) were squamous cell carcinoma, while 36 cases (36/44, 81.8%) were mixed squamous cell carcinoma. The mixed components included non-specific carcinoma and spindle cell metaplastic carcinoma (17 cases each). One case contained ductal carcinoma in situ of the breast and 1 case contained tubular carcinoma. The proportion of squamous cell carcinoma was 10% to 90%. The cases with pure squamous cell carcinoma often had a large cystic cavity, which was lined by atypical squamous epithelium, while infiltrating squamous cell carcinoma nests were seen in the breast tissue around the cystic cavity. Immunohistochemical staining showed that p63 and CK5/6 were expressed in the squamous cell carcinoma component, but ER, PR and HER2 were not, except for one case of HER2 1+. The positive rates of TRPS1 and PDL-1 were 76% and less than 1%, respectively. Fifteen cases were in the high TILs group (TILs≥30%) and 29 cases were in the low TILs group (TILs<30%). Twenty-three patients were followed up for 5 to 118 months. Among them, 12 died within 3 years and 9 were alive at the end of the follow up. There was no significant difference in TNM stage, TILs and prognosis between simple squamous cell carcinoma and mixed squamous cell carcinoma. Conclusions: Breast squamous cell carcinoma can be divided into simple squamous cell carcinoma and mixed squamous cell carcinoma. There are differences in gross findings and histology between the simple and mixed squamous cell carcinoma of the breast. Sufficient samples should be taken to avoid missing the diagnosis of a minor squamous component. The prognosis of patients with high TILs is significantly better than that of patients with low TILs. The expression rate of TRPS1 in primary squamous cell carcinoma of breast is high and helpful to the differential diagnosis from metastatic squamous cell carcinoma.

[Congenital spindle cell/sclerosing rhabdomyosarcoma: a clinicopathological analysis].

Objective: To investigate the clinicopathological features, immunophenotype and molecular genetic characteristics of congenital spindle cell/sclerosing rhabdomyosarcoma. Methods: Sixteen cases (including 10 consultation cases) of congenital spindle cell/sclerosing rhabdomyosarcoma diagnosed at the Beijing Children's Hospital, Capital Medical University, Beijing China, from April 2017 to January 2022 were collected. These cases were evaluated for clinical profiles, histomorphological features, immunophenotype and molecular characteristics. Results: Among the 16 patients, 9 were male and 7 were female. Five cases were present during maternal pregnancy and 11 cases were found immediately after birth. The tumors were located in the chest wall, low back, retroperitoneum, extremities or perineum. The tumors consisted of fasciculated spindle-shaped cells with localized mesenchymal sclerosis and vitreous metaplasia. Immunohistochemistry showed that the tumor cells expressed Desmin, Myogenin, MyoD1, SMA, CD56 and ALK to varying degrees, but not other markers such as CD34, CD99, pan-TRK, S-100 and BCOR. FISH analyses with NCOA2 (8q13) and VGLL2 (6q22) gene breakage probes revealed a breakage translocation in chromosome NCOA2 (8q13) in 4 cases (4/11). In the 6 cases subject to sequencing, a mutation at the p.L122R locus of MYOD1 gene was detected in 1 case (1/6). Two cases were examined by electron microscopy, which showed bundle-arranged myofilaments with some primitive myofilament formation. Five cases were resected with simple surgery, 2 cases were biopsied and followed up with observation only, and 9 cases were treated with surgery and adjuvant chemotherapy. Follow-up was available in 12 cases. At the end of the follow-up, 2 of the 12 patients developed local recurrences and 2 patients survived with disease. Conclusions: Congenital spindle cell/sclerosing rhabdomyosarcoma is a rare subtype of congenital rhabdomyosarcoma. It more commonly occurs in the chest, back and lower limbs of infants than other sites. NCOA2/VGLL2 gene fusion seems to be the most common genetic change. Its prognosis is better than other subtypes of rhabdomyosarcoma and those in adolescents and adults with the same subtype. Analysis and summary of its clinicopathological features can help differentiate it from other soft tissue tumors in infants and children and provide the information for appropriate treatments.

[Interpretation of myeloid neoplasms in the 5th WHO classification of haematolymphoid tumors].

The 5th edition of the WHO classification of haematolymphoid tumors ß version had been released online, in which the section of myeloid neoplasms had undergone significant changes in the classification framework,standards of diagnosis and classification criteria. The principle of comprehensive diagnosis based on clinicopathologic multi-parameter was maintained, especially strengthening the priority importance of biological features in diagnosis and classification, and highlighting the biological characteristics of the disease and thus providing the basis for targeted treatment and prognostic evaluation. This article introduces the main updates and changes in the myeloid neoplasms of the 5th edition of the WHO haematolymphoid tumor classification, in order to better understand and guide clinical diagnosis and therapeutic treatment in the future.

MicroRNA expression as a prognostic biomarker of tongue squamous cell carcinoma (TSCC): a systematic review and meta-analysis.

BACKGROUND: Recent studies have indicated that microRNA (miRNA) expression in tumour tissues has prognostic significance in Tongue squamous cell carcinoma (TSCC) patients. This study explored the possible prognostic value of miRNAs for TSCC based on published research. METHODS: A comprehensive literature search of multiple databases was conducted according to predefined eligibility criteria. Data were extracted from the included studies by two researchers, and HR results were determined based on Kaplan‒Meier curves according to the Tierney method. The Newcastle‒Ottawa Scale (NOS) and GRADE (Grading of Recommendations Assessment, Development, and Evaluation) pro-GDT were applied to assess the quality of all studies. Publication bias was estimated by funnel plot, Egger's rank correlation test and sensitivity analysis. RESULTS: Eleven studies (891patients) were included, of which 6 reported up-regulated miRNAs and 7 mentioned down-regulated miRNAs. The pooled hazard ratio (HR) from the prognostic indicator overall survival (OS) was 1.34 (1.25-1.44), p < 0.00001, indicating a significant difference in miRNA expression between TSCC patients with better or worse prognosis. CONCLUSION: MiRNAs may have high prognostic value and could be used as prognostic biomarkers of TSCC.

The prognosis of patients treated with everolimus for advanced ER-positive, HER2-negative breast cancer is driven by molecular features.

Everolimus is widely used in patients with advanced ER-positive, HER2-negative breast cancer. We looked at alterations in the PIK3CA/AKT/mTOR pathway in a multicenter cohort as potential biomarkers of efficacy. Patients with advanced ER-positive, HER2-negative breast cancer treated with everolimus and endocrine therapy between 2012 and 2014 in two cancer centers were included. Targeted sequencing examined mutations in PIK3CA, ESR1, and AKT1 genes. An immunochemical analysis was conducted to evaluate expression of PTEN, INPP4B, STK11, p4EBP1, and pS6. We analyzed 71 patients (44 primary tumors; 27 metastatic tissues). Median age was 63 years [58-69]. All patients had heavily pretreated advanced disease. A mutation in the PIK3CA pathway was observed in 32 samples (PIK3CA exons 10 and 21 and AKT1 exon 4 in 15.5%, 24.0%, and 5.6% of samples), and in ESR1 in 5 samples (7.0%), respectively. Most samples showed cytoplasmic expression of the PIK3CA pathway proteins. Progression-free survival was longer in patients with a pS6 or p4EBP1 histoscore ≥ median value (6.6 versus 3.7 months, p = 0.037), and in patients with a PTEN histoscore ≤ median value (7.1 versus 5.3 months, p = 0.02). Overall survival was longer in patients with pS6 ≥ 3rd quartile (27.6 versus 19.3 months, p = 0.038) and in patients with any mutation in the PIK3CA/AKT/mTOR pathway (27.6 versus 19.3 months, p = 0.011). The prognosis of patients treated with everolimus for advanced ER-positive, HER2-negative breast cancer appears primarily driven by molecular features associated with the activation of the PIK3CA/AKT/mTOR pathway.

Prognostic value of depression and anxiety on colorectal cancer-related mortality: a systematic review and meta-analysis based on univariate and multivariate data.

BACKGROUND: Depression and anxiety are common mental disorders in patients with colorectal cancer (CRC); however, it remains unclear whether they are related to cancer mortality. METHOD: Based on a systematic literature search, 12 eligible studies involving 26,907 patients with CRC were included in this study. RESULTS: Univariate analysis revealed that anxiety was associated with an all-cause mortality rate of 1.42 (1.02, 1.96), whereas multivariate analysis revealed that anxiety was not associated with an all-cause mortality rate of 0.73 (0.39, 1.36). In univariate and multivariate analyses, depression was associated with all-cause mortality rates of 1.89 (1.68, 2.13) and 1.62 (1.27, 2.06), respectively, but not with the cancer-associated mortality rate of 1.16 (0.91, 1.48) in multivariate analyses. Multivariate subgroup analysis of depression and all-cause mortality showed that younger age (≤65 years), being diagnosed with depression/anxiety after a confirmed cancer diagnosis, and shorter follow-up time (<5 years) were associated with poor prognosis. CONCLUSIONS: Our study emphasizes the key roles of depression and anxiety as independent factors for predicting the survival of patients with CRC. However, owing to the significant heterogeneity among the included studies, the results should be interpreted with caution. Early detection and effective treatment of depression and anxiety in patients with CRC have public health and clinical significance.

UTRN as a potential biomarker in breast cancer: a comprehensive bioinformatics and in vitro study.

Utrophin (UTRN), known as a tumor suppressor, potentially regulates tumor development and the immune microenvironment. However, its impact on breast cancer's development and treatment remains unstudied. We conducted a thorough examination of UTRN using both bioinformatic and in vitro experiments in this study. We discovered UTRN expression decreased in breast cancer compared to standard samples. High UTRN expression correlated with better prognosis. Drug sensitivity tests and RT-qPCR assays revealed UTRN's pivotal role in tamoxifen resistance. Furthermore, the Kruskal-Wallis rank test indicated UTRN's potential as a valuable diagnostic biomarker for breast cancer and its utility in detecting T stage of breast cancer. Additionally, our results demonstrated UTRN's close association with immune cells, inhibitors, stimulators, receptors, and chemokines in breast cancer (BRCA). This research provides a novel perspective on UTRN's role in breast cancer's prognostic and therapeutic value. Low UTRN expression may contribute to tamoxifen resistance and a poor prognosis. Specifically, UTRN can improve clinical decision-making and raise the diagnosis accuracy of breast cancer.