Independent Prognostic Factor Research Articles

Pan-cancer landscape analysis of NOP58 and its oncogenic driving role in lung adenocarcinoma.

Despite improvements in treatment in recent years, patients with lung adenocarcinoma (LUAD) still face poor prognoses. In this study, we elucidated the potential role of NOP58 ribonucleoprotein in pan-cancer and validated its oncogenic significance in LUAD using bioinformatics and in vitro and in vivo functional assays. NOP58 was found to be overexpressed in various types of tumors. It had great precision for predicting 20 distinct cancer types using receiver operating characteristic curve (ROC) as well as significant connections with the prognoses in particular cancers. In LUAD, NOP58 expression was correlated substantially with the TNM stage, pathologic stage, smoking status, and effectiveness endpoints, when we analyzed its association with clinical characteristics in LUAD. Elevated NOP58 expression was shown as connected with Th2 cell infiltration while also negatively linked with infiltrating other immune cells, such as CD8 T, cytotoxic, and Th1. By inhibiting NOP58 within the LUAD cells, we found a decrease in cells' capability to proliferate, migrate, and invade. Knockdown of NOP58 inhibited tumor growth in mouse xenograft models. Furthermore, the tissue microarray study indicated that there was a greater expression of NOP58 in the tumor tissues compared to adjacent normal tissues in LUAD. Our findings revealed that NOP58 could be an outstanding bio-index for pan-cancer diagnosis and prognosis and an independent prognostic risk factor in LUAD.

CNSC-45. EXTRINSIC ELECTRICAL MODULATION IMPACTS GLIOBLASTOMA TUMOR GROWTH BY DISRUPTING ITS INTERCELLULAR COMMUNICATION

Abstract Glioblastoma (GBM) is an incurable primary malignant neoplasm of the central nervous system. GBM as an electrically active neoplasm diffusely colonizes healthy brain tissues, disrupting the neurotransmission balance and causing glioma-related epilepsy (GRE) in up to 50% of patients. Interestingly, GRE is an independent favorable prognostic factor for survival in GBM. The therapeutic induction of seizure may have a previously unexplored oncologic value in GBM. We have previously reported in CT-2A-bearing mice subjected to daily extrinsic electrical modulation (EEM) diminished tumor progression and increased overall survival relative to sham-treated mice, but the mechanism by which EEM produces its anti-tumor effect remains uncertain. Therefore, GBM-bearing mice (CT-2A cells xenografted into 5-7 weeks old C57BL/6 female mice, n=5/group) received either a single EEM of 2.0 millicoulombs (mC) or sham treatment. The mice were terminated at 3 hours, 24 hours, 4, 7, and 10 days post-EEM, and tumors and contralateral brain cortex were analyzed using bulk RNA-sequencing and Sequential immunofluorescence (SeqIFTM). SeqIFTM revealed how EEM activates neuronal activity via cFOS expression and induces tumor-specific cell damage through cleaved caspase-3 expression, without affecting healthy brain tissue. Furthermore, RNA-seq performed post-EEM revealed gene expression changes of not only synapse organization markers but also of several tumor-tumor and tumor-neuron connectivity key markers, such as growth-associated protein 43 (GAP43), neuroligin-3 (NLGN3), and glutamate receptors such as GRIA4 and GRIN1 between others. However, the expression of these markers diminished significantly 96h after-EEM, indicating a reduction in intercellular electrical communication by the inhibition of the neoplasm cells electrical integration with neuronal circuits by downregulating glutamatergic receptor expression, blocking the synapse-forming protein NLGN3, and the network-connecting protein GAP43. Taken together, our findings reveal how by the disruption of these critical interactions within the tumor microenvironment though EEM impacts on GBM growth making it more susceptible to therapeutic interventions.

PATH-14. UTILITY OF DNA METHYLATION ANALYSIS IN HISTOLOGICALLY-CONFIRMED PA PATIENTS WITH POOR PROGNOSIS

Abstract INTRODUCTION Pilocytic astrocytoma (PA) is a circumscribed low-grade astrocytic glioma, generally considered to be associated with a good prognosis. However, some PA patients experience unfavorable outcomes; advanced age was known as an independent poor prognostic factor. This study retrospectively reviewed PA patients and conducted molecular analyses for elderly patients. METHODS We analyzed data from 29 histologically confirmed PA patients treated at a single center from 2002 to 2021 and conducted integrated molecular analyses including DNA methylation profiling for elderly PA patients. RESULTS The median age at diagnosis was 14 years (range 3-82 years), with 4 patients (14%) being elderly (patients≥60years old). Elderly patients had significantly worse progression-free survival and overall survival. DNA methylation analysis was performed on 2 of the 4 elderly patients. Despite histological diagnoses of PA, methylation profiling classified one case as high-grade astrocytoma with piloid features (methylation class scores below 0.3 in both v11b4 and v12.5) and the other as glioblastoma, IDH-wildtype (score over 0.5 in both v11b4 and v12.5), using classifiers from the German Cancer Research Center and t-SNE analysis. CONCLUSION Elderly patients with PA morphology showed unfavorable outcomes in this cohort. In those patients, DNA methylation profiling revealed the possibility of high-grade astrocytic tumors, including newly defined entities.

Predicting first-line VEGFR-TKI resistance and survival in metastatic clear cell renal cell carcinoma using a clinical-radiomic nomogram.

This study aims to construct predicting models using radiomic and clinical features in predicting first-line vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFR-TKI) early resistance in metastatic clear cell renal cell carcinoma (mccRCC) patients. We also aim to explore the correlation of predicting models with short and long-term survival of mccRCC patients. In this retrospective study, 110 mccRCC patients from 2009 to 2019 were included and assigned into training and test sets. Radiomic features were extracted from tumor 3D-ROI of baseline enhanced CT images. Radiomic features were selected by Lasso method to construct a radiomic score. A combined nomogram was established using the combination of radiomic score and clinical factors. The discriminative abilities of the radiomic, clinical and combined nomogram were quantified using ROC curve. Cox regression analysis was used to test the correlation of nomogram score with progression-free survival (PFS) and overall survival (OS). PFS and OS were compared between different risk groups by log-rank test. The radiomic, clinical and combined nomogram demonstrated AUCs of 0.81, 0.75, and 0.83 in training set; 0.79, 0.77, and 0.88 in test set. Nomogram score ≥ 1.18 was an independent prognostic factor of PFS (HR 0.22 (0.10, 0.47), p < 0.001) and OS (HR 0.38 (0.20, 0.71), p = 0.002), in training set. PFS in low-risk group were significantly longer than high-risk group in training (p < 0.001) and test (p < 0.001) set, respectively. OS in low-risk group were significantly longer than high-risk group in training (p = 0.003) and test (p = 0.009) set, respectively. A nomogram combining baseline radiomic signature and clinical factors helped detecting first-line VEGFR-TKI early resistance and predicting short and long-term prognosis in mccRCC patients.

CNSC-21. THE EFFICACY OF TUMOR TREATING FIELDS IN TREATING IDH-MUTANT ASTROCYTOMA, WHO GRADE 4: AN EARLY RESULT FROM SHANGHAI HUASHAN HOSPITAL

Abstract OBJECTIVES There is ongoing debate regarding the efficacy of Tumor Treating Fields (TTFields) for treating IDH-mutant grade 4 astrocytoma (IDHmA4). In fact, the evidence supporting TTFields in treating IDHmA4 is largely extrapolated from EF-14, of which the results stem form heterogeneous entities of glioblastoma lack of IDH status. This study was conducted by reviewing the database in our center following the release of WHO CNS 5, aiming to preliminarily explore the efficacy of TTFields and prognosticators of newly-diagnosed IDHmA4. METHODS This retrospective analysis included 53 consecutive patients with newly-diagnosed IDHmA4, who underwent radiotherapy at Huashan Hospital, Fudan University between September 2021 and December 2023. All patients were administered with concurrent and adjuvant temozolomide. Eleven patients received adjuvant TTFields after surgery. Information regarding patient baseline characteristics, treatment approaches and molecular markers were collected with the purpose of analyzing prognostic factors. RESULTS The median follow-up was 15.7 months. At the time of data cutoff of this analysis, 20 patients had tumor relapse; 3 patients died, all of them were without TTFields therapy. The most common tumor failure pattern was local recurrence (80%, 16/20). The median PFS for the entire cohort was 19.3 months, the median OS was not reached. Univariate analysis indicated that patients who received TTFields therapy tended to have longer median PFS than that of patients without TTFields therapy (24.4 months vs. 18.5 months, P=0.097). Additionally, patients younger than 40 years (24.4 vs. 18.5 months, P=0.107) or without homozygous deletion of CDKN2A/B (23.7 vs. 18.0 months, P=0.108) tended to have better median PFS. No significant independent prognostic factor was found in the multivariate analysis. CONCLUSIONS The overall prognosis of IDHmA4 is poor. TTFields may help to improve the outcome of patients with newly-diagnosed IDHmA4. Longer follow-up, larger sample size and prospective clinical trials are warranted for deeper comprehension.

MET amplification correlates with poor prognosis and immunotherapy response as a subtype of melanoma: a multicenter retrospective study.

Mesenchymal epithelial transition factor (MET) variant is an independent prognostic factor for worse prognosis in patients with lung cancer or gastroesophageal adenocarcinoma. MET gene variants can be regarded as a subtype of melanoma but there is a lack of studies regarding the frequency of MET genetic alterations and the efficacy of immunotherapy in melanoma patients. The purpose of this study is to explore potential therapeutic strategies for melanoma subtypes with MET alterations. A total of 1751 malignant melanomas were analyzed to illustrate the landscape of MET mutations. We collected 55 melanoma cases from multicenter for a retrospective cohort from 2010 to 2023. We analyzed the impact of MET amplification on the efficacy of immunotherapy in the retrospective cohort after propensity score matching (PSM) and a pancancer cohort. CIBERSORT was used to evaluate the immune infiltration. There were no instances of MET 14 exon skipping, and only instances of MET amplification were found in the 1751 melanomas and our retrospective cohort. Cox proportional hazards model analysis showed that MET amplification (P = 0.006) was significantly associated with poorer overall survival (OS) in patients who received immunotherapy as the first-line treatment. Compared with patients with MET amplification, patients in the negative control (NC) group had a significantly better OS (P = 0.022) after PSM. Analysis of 1661 pancancer cases with the MSK-IMPACT assay showed that patients receiving immunotherapy in the MET amplification group had a trend toward worse OS than those without MET amplification (P = 0.025). This database analysis showed that the main type of MET mutation is amplification in malignant melanoma. MET-amplified solid tumors might be considered for targeted therapy, as MET amplification can be regarded as a risk factor affecting the prognosis of patients with tumors treated with immunotherapy.

Factors Contributing to Early Recovery of Urinary Continence Following Radical Prostatectomy: A Narrative Review

Stress urinary incontinence (SUI) is a common condition in patients following radical prostatectomy (RP), which has a significant impact on all aspects of quality of life and is associated with significant social stigma. The factors that improve urinary incontinence in patients following surgery remain controversial. The aim of our narrative review was to identify and synthesise the latest evidence on pre-, intra- and post-operative factors and predictors that contribute to early continence recovery after RP. In this narrative review, primary resources were identified by searching PubMed, EMBASE and Medline, and secondary resources were collected by cross-referencing citations in the relevant articles. We started our review by searching for systematic reviews of factors and predictors that contribute to early recovery of urinary continence after RP. We then reviewed societal guidelines such as the American Urological Association and European Urological Association guidelines on male urinary incontinence. This review focuses on the pre-, intra and postoperative factors that influence postoperative SUI after RP, as well as highlighting modifications in surgical techniques that lead to early continence recovery. Increasing age, higher BMI, shorter membranous urethral length (MUL), and larger PV are independent prognostic factors for SUI within 3 months after RP. Factors such as modified surgical technique preservation of anatomical structure lead to influence postoperative early continence recovery. SUI after RP is influenced by various factors. These factors include not only anatomical landmarks and patient-related factors such as age, BMI, length of MUL and prostate volume, but also prior transurethral resection or laser enucleation of the prostate, the surgeon’s expertise, the surgical approach and NS technique.

Identification of a coagulation-related gene signature for predicting prognosis in recurrent glioma.

Recurrent gliomas rapidly progress and have high mortality and poor prognosis in the central nervous system. Therefore, further investigation of prognostic and therapeutic markers is needed. The mRNA expression, clinical data, and coagulation-related genes (CRGs) associated with recurrent glioma were obtained and calculated from the Chinese Glioma Genome Atlas and Kyoto Encyclopedia of Genes and Genomes databases. The significant CRGs were calculated by Weighted gene co-expression network analysis and PPI network. A prediction model was constructed using the least absolute shrinkage and selection operator regression analysis. Recurrent gliomas were stratified into high and low-risk groups based on the median risk score (RS). The Kaplan-Meier curve was used to analyze the difference in overall survival (OS) between these groups, while the receiver operating characteristic (ROC) curve was used to evaluate the accuracy of the gene model at 1-, 3-, and 5-years. Clinical factors, including age, gender, MGMT methylation status, radiotherapy, chemotherapy, and RS, were included in the univariate and multivariate regression analysis. A prognostic nomogram and calibration curve were established based on these factors. Overall, seven CRGs associated with the prognosis were identified, including BTK, ITGB1, GNAI3, CFH, LYN, CFI, and F3. OS and survival rates were lower in the high-risk group compared with the low-risk group. The ROC curve demonstrated the area under the curve values >0.65 at 1-, 3-, and 5-years, confirming the reliability of the prognostic model. The univariate regression analysis indicated that tumor grade (grades 2, 3, and 4), histopathology (GBM or not), chemotherapy, IDH mutation, and 1p19q co-deletion status were independent prognostic indicators. Univariate and multivariate regression analyses indicated that RS was an independent prognostic factor for patients with recurrent glioma. Immune analysis revealed low infiltration of resting dendritic cells and high expression of programmed death receptor 1 in the high-risk group. This study comprehensively investigated the correlation between CRGs and recurrent glioma prognosis, offering crucial insights for further research into glioma recurrence mechanisms and treatment strategies.

CNSC-16. ASSOCIATION BETWEEN RESTING-STATE-NETWORK FUNCTIONAL CONNECTIVITY AND SURVIVAL IN RECURRENT GLIOMAS DIAGNOSED USING FET PET

Abstract BACKGROUND Functional connectivity between glioma-infiltrated brain tissue and remote cortical regions has been linked to overall survival (OS) in patients with newly diagnosed glioblastoma. We studied the association of functional connectivity between tumor and resting-state networks and OS in patients with recurrent gliomas. PATIENTS AND METHODS The study included 82 patients (26-81 years; median ECOG performance score, 0) with recurrent gliomas (grade 4 glioblastoma, n=57; grade 3 and 4 astrocytoma, n=12; grade 2 and 3 oligodendroglioma, n=13) who had undergone first-line therapy. Diagnosis of recurrence was confirmed by amino acid PET using the tracer O-(2-[18F]-fluoroethyl)-L-tyrosine (FET). FET PET and resting-state functional MRI were simultaneously acquired on a 3T hybrid PET/MR scanner. We performed a seed-based dual regression analysis to determine the functional connectivity between metabolically active tumors and seven canonical resting state networks. RESULTS Average functional connectivity was highest in oligodendrogliomas (z-score, 6.9±1.9) and was inversely related to the tumor grade (p=0.031). Univariate Cox regression analysis revealed a significant (p&amp;lt;0.05) positive association between OS and tumor connectivity with the visual, somatomotor, and dorsal attention networks. Subsequent stepwise multivariate Cox regression analysis refined this association to the dorsal attention network alone (HR, 0.88; 95% CI, 0.80-0.97; p=0.007). Patients with the highest functional connectivity (z-score&amp;gt;8.3, n=21) had a median OS of 31.4 months, while those with the lowest functional connectivity (z-score&amp;lt;4.3, n=21) had 10.6 months. Functional connectivity between tumors and the dorsal attention network showed an independent association with OS (HR, 0.90; 95% CI, 0.81-0.99; p=0.033) in a multivariate model, including various prognostic factors. CONCLUSION Recurrent gliomas exhibit significant functional connectivity to most of the major known resting-state networks, highest in oligodendrogliomas. The data suggest that high functional connectivity between the tumor and the dorsal attention network is an independent prognostic factor for improved OS.

CTNI-13. 18-FET-PET ENHANCED DIAGNOSIS OF PSEUDOPROGRESSION IN GLIOBLASTOMA IS AN INDEPENDENT PROGNOSTIC FACTOR FOR OVERALL SURVIVAL

Abstract INTRODUCTION Detecting pseudoprogression (PSP) in glioblastoma during first-line treatment remains challenging and has significant clinical implications for patient management. The detection of PSP has been shown feasible using FET-PET. The prognostic impact of FET-PET diagnosed PSP on overall survival is still uncertain, as retrospective studies provide limited insights due to the substantial differences in the distribution of prognostic factors between tumor progression (TP) and PSP groups. This study aims to address these uncertainties by leveraging advanced analysis techniques. METHODS Patients with newly diagnosed glioblastoma (WHO 2021) who underwent chemoradiation and contrast-enhanced MRI suspected for TP and subsequent FET-PET scan at Essen University Hospital were retrospectively evaluated. The modified Response Assessment in Neuro-Oncology (RANO) criteria were used to diagnose PSP. FET-PET analysis included mean (TBRmean) and maximum tumor-to-brain ratios (TBRmax). The two groups (TP/PSP) were balanced using a propensity score analysis including age at diagnosis, extent of resection, Karnofsky-Performance-Status Scale (KPS) and MGMT methylation status. Overall survival was predicted using Kaplan-Meier and multivariate analysis as well as conventional FET-PET parameters, PET/MRI volumetry, and FET/MRI-derived radiomics. An independent cohort was used for validation. RESULTS Out of the 165 patients analysed in this study, 38 were diagnosed with PSP. Following balancing analysis, our study cohort consisted of 40 patients (20 TP/20 PSP). Patients with PSP had a significantly longer mean overall survival (mOS) compared to those with TP (mOS TP 20.24 months; mOS PSP 33.25 months; p=0.0023). The multivariate Cox-Regression analysis confirmed PSP as a significant prognostic marker for overall survival (p=0.0153). Confirmation of these results on an independent validation cohort is pending and will be presented at the meeting. CONCLUSION This study shows that PSP is an independent prognostic factor for overall survival in newly diagnosed glioblastoma patients.

A nomogram model to predict recurrence of early-onset endometrial cancer after resection based on clinical parameters and immunohistochemical markers: a multi-institutional study

ObjectiveThis study aimed to investigate the prognosis value of the clinical parameters and immunohistochemical markers of patients with early-onset endometrial cancer (EC) and establish a nomogram to accurately predict recurrence-free survival (RFS) of early-onset EC after resection.MethodsA training dataset containing 458 patients and an independent testing dataset consisting of 170 patients were employed in this retrospective study. The independent risk factors related to RFS were confirmed using Cox regression models. A nomogram model was established to predict RFS at 3 and 5 years post-hysterectomy. The C-index, area under the curve (AUC) of the receiver operating characteristic (ROC) curve, and calibration curve were calculated to assess the predictive accuracy of the nomogram.ResultsIn all early-onset EC patients, more than half (368/628, 58.6%) were diagnosed in the age range of 45-49 years. Meanwhile, the recurrence rate of early-onset EC is approximately 10.8%. Multivariate Cox regression analyses showed that histological subtype, FIGO stage, myometrial invasion, lymphovascular space invasion (LVSI), P53 expression, and MMR status were independent prognostic factors related to RFS (all P &amp;lt; 0.05) and established the nomogram predicting 3- and 5-year RFS. The C-index and calibration curves of the nomogram demonstrated a close correlation between predicted and actual RFS. Patients were divided into high- and low-risk groups according to the model of RFS.ConclusionsCombining clinical parameters and immunohistochemical markers, we developed a robust nomogram to predict RFS after surgery for early-onset EC patients. This nomogram can predict prognosis well and guide treatment decisions.

RBM15 facilitates osimertinib resistance of lung adenocarcinoma through m6A-dependent epigenetic silencing of SPOCK1.

Lung cancer is the leading cause of cancer-related mortality globally. N6-methyladenosine (m6A) is the most abundant modification in mammalian mRNA and is involved in the biological regulation of tumors, including lung cancer. However, the role of m6A-related proteins, such as RNA-binding motif protein 15 (RBM15), in lung cancer progression remains largely unknown. Our study indicated that RBM15 is significantly overexpressed in lung adenocarcinoma, serving as an independent prognostic factor for poor outcomes and facilitating tumor cell proliferation and migration. RBM15 was markedly elevated in patients with EGFR mutations, correlating with a poorer prognosis, while it had negligible prognostic value in EGFR wild-type patients. As EGFR-tyrosine kinase inhibitors (TKIs) are the standard treatment for patients with EGFR mutations, we subsequently determined that RBM15 drives osimertinib resistance via a novel mechanism: enhancing m6A modification of cwcv- and kazal-like domains proteoglycan 1 (SPOCK1) mRNA, promoting epithelial-mesenchymal transition-mediated osimertinib resistance through a bypass activation pathway. These findings were validated in osimertinib-resistant H1975 cells and organoids from patients with osimertinib-resistant lung adenocarcinoma. Furthermore, the RBM15-SPOCK1 axis was activated in drug-tolerant persister cells, indicating that early targeting of RBM15 during EGFR-TKI treatment could dramatically extend the patient response and benefit from TKI therapy. Our results emphasize the critical role of RBM15 in reversing EGFR-TKI resistance and propose it as a promising therapeutic target for prolonging TKI treatment benefits in patients with lung adenocarcinoma.

TMIC-28. TITLE: AN IMMUNE-RELATED, SEX-SPECIFIC T-CELL SIGNATURE IN GLIOBLASTOMA MICROENVIRONMENT WITH PROGNOSTIC IMPACT

Abstract BACKGROUND Glioblastoma, IDH-wildtype (GBM), is the most prevalent and aggressive primary brain cancer with a poor prognosis. Immune checkpoint inhibitors (ICIs) have been explored in GBM with limited success, highlighting the need for a better understanding of the tumor microenvironment (TME). This study investigated whether the expression of specific immune checkpoints on tissue-resident memory T cells (Trm) predicts patient outcomes. METHODS In a single cohort observational study, tumor samples from 45 histologically confirmed GBM patients were processed to obtain single-cell suspensions. Multiparametric flow cytometry was used to analyze the correlation of Trm phenotypes with overall survival (OS) and progression-free survival (PFS). Univariate and multivariate analyses were conducted to assess the prognostic significance of Trm subsets. RESULTS Low frequency of exausted Trm expressing programmed cell death protein 1 (PD1) and T cell immunoglobulin and mucin domain-containing protein 3 (TIM3) was associated with better clinical outcomes. Multivariate analysis identified low CD8+CD103+PD1+TIM3+ Trm and Karnofsky performance status (KPS) ≥70 as the most significant independent prognostic factors for longer OS (hazard ratios—HR [95%CI]: 0.14 [0.04–0.52] p &amp;lt; 0.001, 0.39 [0.16–0.96] p = 0.04, respectively). Additionally, younger patients (&amp;lt;63 years) and males had distinct immune profiles affecting prognosis. Notably, the proportion of exausted CD8+CD103+PD1+ Trms had a prognostic correlate only in male patients, consistent with findings by other groups on the existance of gender-specific immune TME in GBM. CONCLUSIONS Further exploration of Trm-based immune profiling has the potential to shed light on GBM resistance to ICIs and to help in personalizing treatment strategies.

Clinicopathological features and prognosis of mucinous breast carcinoma with a micropapillary structure.

To conduct a comparative analysis of clinicopathological data between mucinous micropapillary breast carcinoma (MUMPC) and pure mucinous carcinoma (PMC) without a micropapillary structure to elucidate the distinctive clinicopathological characteristics of MUMPC and their impact on prognosis. This retrospective analysis included 325 patients diagnosed with mammary mucinous carcinoma admitted to Tianjin Cancer Hospital between July 2014 and December 2019, including 197 patients with MUMPC and 128 patients with PMC without a micropapillary structure. Clinicopathological features were compared, and factors influencing the prognosis of MUMPC were analyzed. Survival analysis was conducted using the Kaplan-Meier method, and univariate and multivariate prognostic analyses for MUMPC were performed using the Cox proportional hazard regression model. The median follow-up period was 76 months. In the MUMPC and PMC groups, the disease-free survival (DFS) rates at 3, 5, and 7 years were 95.4%, 90.4%, 89.8%, and 100%, 98.4%, and 96.9%, respectively, with a statistically significant difference between the two groups (p = 0.009). Tumor, node, and metastasis (TNM) stage, lymph node metastasis, and endocrine treatment were significant factors influencing the prognosis of the MUMPC group (p < 0.001). Multivariate analysis revealed that lymph node metastasis and endocrine therapy were independent prognostic factors in patients with MUMPC (p < 0.001). Compared with PMC, the MUMPC group exhibited a higher prevalence of HER2 (11.2% vs. 3.1%, p = 0.009) and Ki-67 overexpression (79.7% vs. 60.2%, p < 0.001). The lymph node stage is the most crucial clinicopathological feature of MUMPC. Endocrine treatment strategy is an independent risk factor affecting the prognosis of MUMPC.

Individualised prediction of chemotherapy benefit in early-onset colorectal cancer

PurposesWhether patients with early-onset colorectal cancer (EOCRC) receive chemotherapy has been controversial, so our study aimed to screen patients with EOCRC who benefit from chemotherapy.MethodsA total of 2166 EOCRC patients were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were divided into chemotherapy and non-chemotherapy groups, propensity score matching (PSM) was performed to balance the differences between the groups, and the Kaplan–Meier method was used to calculate the cancer-specific survival (CSS) of EOCRC patients. Multifactorial COX regression analysis was used to identify independent prognostic factors for CSS and to construct a nomogram for predicting CSS in EOCRC patients. The overall risk score was calculated based on Nomogram, and EOCRC patients were classified into high-risk and low-risk groups to assess further chemotherapy's therapeutic effect on patients with different risk stratification.ResultsBefore PSM, patients in the chemotherapy group had poorer CSS (p < 0.001). After PSM, there was no significant difference in patient CSS between the two groups (p = 0.057). Independent prognostic factors (Race, Grade, Pathology, AJCC.N, AJCC.M, CEA, Marital. Status) were screened according to multifactorial COX regression analyses and included in the Nomogram predicting CSS in EOCRC patients. A risk stratification system for EOCRC patients was further developed, and the results showed that chemotherapy had no significant effect on CSS in the low-risk group of patients, but in the high-risk group, chemotherapy significantly improved CSS in EOCRC patients.ConclusionsWe developed a clinical risk model by combining different risk factors, which can accurately screen those with high-risk EOCRC for benefit from chemotherapy. For low-risk EOCRC patients, our results did not observe a better survival benefit from chemotherapy, and more prospective studies are needed in the future to prove our conclusions.

The Risk Genes SIRP5, CMC1, and ASAH1 as Potential Targets for the Diagnosis, Immunotherapy, and Treatment of Colon Adenocarcinoma by Single-Cell and Bulk RNA Sequencing Analysis.

Globally, one of the main causes of cancer-related mortality is Colon Adenocarcinoma (COAD). In this study, a new special Immune Cell Functions (ICF) risk model was constructed using single-cell and bulk RNA sequencing data to develop a new understanding and clinical applications for COAD. The immune function gene sets were downloaded from a literature reference, and the COAD single-cell dataset GSE146771 was downloaded from the Tumour Immune Single Cell Hub database. Using Lasso analysis, a multiple gene signature was made from the enrichment scores of immune function gene sets that were enriched in different ways. Robust validation of the signature was then performed in multiple independent cohorts. After that, we built the model using a 10-fold cross-test and evaluated its independence for clinical usage using a nomogram. We also investigated the connection between signature and immune function, genetic variation, immunotherapy, and the cancer immunological microenvironment. Lastly, we used qPCR and immunohistochemistry to examine the expression of the unreported model genes. To find the regulatory functions of unreported model genes, an EdU assay was employed. First, 20 differentially enriched immune function gene sets were identified. Ten genes can be used as a risk profile to assess the prognosis of colon cancer, according to Lasso regression analysis. Signature performance was stable in both the training cohort and two independent GEO external cohorts, and risk scores were confirmed as independent prognostic factors. At the same time, our risk model continued to be highly predictive across various clinical clusters and clinical characteristics, such as immune checkpoints, tumour genome mutations, and chemotherapeutic drug resistance. Patients in the low-risk group have exhibited a higher chance of benefiting from immunotherapy, according to immunotherapy response research. qPCR and immunohistochemistry analysis have revealed SIRP5 expression as high in COAD tissues, while CMC1 and ASAH1 expression has been found to be low. According to the findings of the functional experiment, SIRP5, CMC1, and ASAH1 may control the ability of CRC cells to proliferate. In this study, using scRNA-seq and bulk RNA-seq data, we created a risk model to predict the prognosis and effectiveness of immunotherapy in patients with COAD. In addition, we have discovered three model genes (SIRP5, CMC1, and ASAH1) that have not been reported before. These genes have the potential to be novel therapeutic targets in Colorectal Cancer (CRC). These findings suggest that this model could be used to evaluate the prognostic risk and identify potential targets for COAD patient treatment.

International Metabolic Prognostic Index Is Superior to Other Metabolic Tumor Volume-Based Prognostication Methods in a Real-Life Cohort of Diffuse Large B-Cell Lymphoma.

Baseline metabolic tumor volume (MTV) is a promising prognostic marker in diffuse large B-cell lymphoma (DLBCL). We assessed the prognostic value of 4 novel metabolic risk scores in a real-life DLBCL cohort and compared them with the revised international prognostic index (IPI). Methods: We included a consecutive series of untreated DLBCL, not otherwise specified cases that were diagnosed in our hospital from 2008 to 2021 with available baseline [18F]FDG PET/CT. Clinical data were collected retrospectively, including the individual components of the revised IPI. MTV and other radiomic features, including lesion dissemination and tumor volume surface ratio, were calculated. Four novel metabolic risk scores including the international metabolic prognostic index (IMPI), the MTV/World Health Organization performance status, the MTV/standardized maximum distance, and clinical PET models were used to calculate the risk of progression using predefined cutoffs. Survival outcomes considered were 3-y progression free survival (PFS), 3-y time to progression (TTP), and 3-y overall survival (OS). The Harrell C-index was used to assess the discriminative performance of the risk scores. A multivariable model was built. Results: We included 355 DLBCL, not otherwise specified cases with a median MTV of 219 cm3 (range, 0-5,656 cm3). The IMPI had the highest C-index for 3-y PFS, 3-y TTP, and 3-y OS among the 4 metabolic risk scores (0.674, 0.696, and 0.677, respectively). For the 3-y TTP, the IMPI outperformed the strongest clinical risk score, the IPI, although the difference in the Harrell C-indices was small (0.696 vs. 0.693). Regarding the 3-y PFS and 3-y OS, the IPI has the highest C-index of all risk scores (0.696 and 0.693). The IMPI, the MTV/World Health Organization performance status, and the IPI score can recognize a poor risk group with a 3-y OS below 50% (43%, 32%, and 39%, respectively). In multivariable analysis, the IMPI remains an independent prognostic factor (P = 0.0089; hazard ratio, 1.207; 95% CI, 1.048-1.389). MTV and standardized maximum distance have the strongest prognostic values when used as a continuous variable. The tumor volume surface ratio has no significant prognostic value in our analysis. Conclusion: The IMPI has the strongest prognostic performance compared with the other 3 novel metabolic risk scores. However, in our real-world dataset, the IMPI could not replace the IPI, and further prospective trials are needed to compare their performance.

Is Adjuvant Therapy Necessary for Stage IB Gastric Cancer: A Retrospective Cohort Study.

The benefit of adjuvant therapy for patients with IB gastric cancer (GC) is a topic of debate. This study aimed to evaluate the benefit of adjuvant therapy for patients with IB GC. Overall, the study selected 510 IB GC patients after gastrectomy at the First Medical Center of the Chinese PLA General Hospital, Beijing, China between 2005 and 2018. Overall survival (OS) and disease-free survival (DFS) were analyzed using the Kaplan-Meier method and the log-rank test. Cox regression analyses were used to confirm the independent prognostic factors. Patients who received postoperative adjuvant therapy had a longer 5-year OS (92.9 %) than those who received surgery alone (86.7 %; P < 0.05), but the 5-year DFS did not differ significantly between the two groups (92.6 vs. 95.0 %; P > 0.05). Moreover, DFS did not differ between monotherapy, and combination therapy. Uni- and multivariate analyses showed that older age was a significant risk factor for tumor recurrence. Subgroup analyses also failed to identify suitable candidates for chemotherapy. Because adjuvant therapy did not demonstrate any benefits in terms of tumor recurrence or DFS, these treatment strategies may be unnecessary for IB GC patients after gastrectomy. Further studies are required to identify subgroups of IB GC patients who may benefit from adjuvant treatments.

Preoperative anemia is associated with increased length of stay in adult spinal deformity surgery: evaluation of a large single-center patient cohort and future suggestions for patient optimization.

This study aimed to investigate the relationship of preoperative hemoglobin levels as an independent prognostic factor for hospital and intensive care unit (ICU) length of stay (LOS) in patients undergoing surgery for adult spinal deformity (ASD), with the intent of determining whether there exists a correlation and enhancing patient preoperative optimization protocols. The authors reviewed consecutive patients who underwent elective thoracolumbosacral posterior spinal fusion (PSF) involving six or more vertebrae for ASD from January 1, 2013, to December 13, 2021, with a minimum follow-up period of two years. This study primarily investigated the association of preoperative hemoglobin levels with hospital and ICU LOS. To analyze the data, both unadjusted and adjusted generalized linear models (GLM), incorporating cubic splines for non-linear variables, were applied. A total of 598 patients were included. GLMs for hospital and ICU LOS demonstrated nonlinear relationships with preoperative hemoglobin levels. Specifically, hospital LOS decreased with increasing preoperative hemoglobin until a significance threshold of 13.5g/dl. Similarly, ICU LOS significantly decreased with increasing preoperative hemoglobin until 13.0g/dl. Lower preoperative hemoglobin was associated with more perioperative transfusions, less likely discharge to home, and greater risk of reoperation. Preoperative anemia is an independent non-linear risk factor that significantly affects LOS, disposition, and outcomes after surgery for ASD. These findings advocate for a systemic preoperative approach and highlight the need for future research to improve postoperative outcomes and reduce hospital resource utilization. IV.

Nucleolar casein kinase 2 alpha as a prognostic factor in patients with surgically resected early‑stage lung adenocarcinoma.

Lung cancer remains a leading cause of global cancer‑related deaths, therefore the identification of prognostic factors for lung cancer is critical. Casein kinase 2 alpha (CK2α) is one of the driver kinases in various cancers, and it was previously demonstrated that CK2α localization was associated with a poor prognosis in invasive breast cancer. In the present study, the importance of CK2α in the nucleolus was explored as a potential prognostic marker for surgically resected early‑stage lung adenocarcinoma. The present study included 118 patients who underwent pulmonary lobectomy between 2014 and 2018 in Fukushima Medical University Hospital (Fukushima, Japan), and in whom CK2α localization in tumor samples was assessed by immunohistochemistry. Patient and tumor characteristics, including pathological stage, histological type and histological grade, were analyzed. Recurrence‑free survival (RFS) and overall survival were evaluated in relation to nucleolar CK2α staining. CK2α staining in the nucleoli was observed in 50.8% of lung adenocarcinoma tumors. Positive nucleolar CK2α staining was independent of pathological stage, histological type and histological grade. Patients with positive nucleolar CK2α staining exhibited significantly worse RFS compared with patients with negative staining. Multivariate analysis identified nucleolar CK2α staining and lymph node metastasis as independent poor prognostic factors. The results of the present study suggested that nucleolar CK2α staining is a novel and independent prognostic factor in surgically resected early‑stage lung adenocarcinoma. These findings indicated the potential of nucleolar CK2α as a predictive biomarker for future recurrence, and a guide to treatment decisions. Further research is required, particularly in understanding the molecular mechanisms linking nucleolar CK2α to recurrence.