Disease-specific Survival Research Articles

Treatment Outcomes of Squamous Cell Carcinoma of the Soft Palate and the Prognostic Significance of HPV/p16 Status.

Squamous cell carcinoma of the soft palate (SCCSP) represents a rare subtype of oropharyngeal cancer. This study aims to evaluate the treatment outcomes of SCCSP and to assess the prognostic significance of HPV status. Patients diagnosed with SCCSP between January 1981 and December 2021 were collected. Survival outcomes were compared. RESULTS $$ \MATHRM{RESULTS} $$: In univariate analysis, primary surgery resulted in superior progression-free survival (PFS), overall survival (OS), and disease-specific survival (DSS) compared with definitive radiotherapy (p < 0.05). Furthermore, multivariate analysis revealed that primary surgery independently correlated with superior PFS (HR = 0.37, p = 0.002), OS (HR = 0.55, p = 0.012), and DSS (HR = 0.45, p = 0.020) in early-stage SCCSPs. Additionally, no significant prognostic differences were observed between HPV/p16 positive and HPV/p16 negative SCCSPs (p > 0.05). CONCLUSION $$ \MATHRM{CONCLUSION} $$: Surgery yields superior oncological outcomes for early-stage SCCSP patients. HPV status does not demonstrate prognostic significance in SCCSP.

Risk of secondary myeloid neoplasms following treatment in patients with grade I–II follicular lymphoma: a retrospective cohort study

BackgroundTo assess the association between initial treatment modalities and the risk of developing subtypes of myeloid neoplasms (MNs) in survivors with grade I-II follicular lymphoma (FL) and to evaluate their impact on survival outcomes.MethodsPatients diagnosed with grade I–II FL as their first malignancy were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Fine-Gray competing risk regression and Poisson regression were used to evaluate the treatment-associated risk (RR) for MNs and the Kaplan–Meier method was applied to assess the survival outcomes.ResultsAmong 19,326 FL patients, 9539 patients (49.36%) received chemotherapy, and 2890 patients (14.95%) received radiotherapy as part of their initial treatment. With a median follow-up time of 103 months, 90, 82, and 23 patients developed myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and myeloproliferative neoplasms (MPN), respectively. In both multivariable competing risk regression analysis and Poisson regression analysis, chemotherapy was found to be associated with a higher risk of developing MDS (adjusted hazard ratio (HR), 1.85; 95% confidence interval (CI), 1.13–3.02; adjusted RR, 1.88; 95% CI, 1.18–3.04), total AML (adjusted HR, 2.22; 95% CI, 1.33–3.71; adjusted RR, 2.24; 95% CI, 1.37–3.78), and AML with myelodysplasia-related changes (AML-MRC) (adjusted HR, 3.42; 95% CI, 1.24–9.44; adjusted RR, 3.48; 95% CI, 1.52–9.07). Additionally, radiotherapy also increased the risk of AML-MRC (adjusted HR, 2.74; 95% CI, 1.12–6.72; adjusted RR, 2.73; 95% CI, 1.10–6.08). The development of AML or MDS was associated with worse overall survival (OS) and disease-specific survival (DSS) in grade I–II FL survivors.ConclusionInitial chemotherapy and radiotherapy in patients with grade I–II FL were associated with increased risk of certain subtypes of MNs, such as MDS and AML. The importance of balancing risks and benefits should be emphasized in initial FL treatment.

Rare but Complex: Outcomes and Challenges in Managing Composite Follicular-Anaplastic Thyroid Cancer.

A subset of follicular thyroid cancers (FTC) can dedifferentiate into anaplastic thyroid cancer (ATC), forming composite FTC/ATC tumors. The effect of this dedifferentiation on survival outcomes remains unclear. This study aimed to characterize the clinicopathologic features of composite FTC/ATC tumors and assess their disease-specific survival (DSS). The Surveillance, Epidemiology, and End Results (SEER) database (2000-2020) was used to identify patients with FTC, composite FTC/ATC, and ATC. Propensity score matching (PSM) was performed on the basis of age, sex, race, and histologic subtype. Clinicopathologic characteristics, DSS, and treatment outcomes were compared. A total of 60 patients with composite FTC/ATC were matched to 180 patients with FTC and 180 patients with ATC. Compared with FTC, composite tumors were associated with larger size (p < 0.001), extra-thyroidal extension (ETE) (p < 0.001), lymph node (p < 0.001) and distant metastases (p = 0.002), more external beam radiation (p < 0.001), and chemotherapy (p < 0.001), but less radioactive iodine (RAI) (p < 0.001). Compared with ATC, composite tumors showed less ETE (p = 0.01), fewer lymph node metastases (p = 0.01), less chemotherapy (p = 0.002), and more RAI (p = 0.002). The median survival of patients with co-FTC/ATC was 7 months (p < 0.001). Advanced age (hazard ratio, HR 1.05; 95% confidence intervals, CI 1.02-1.08) and incomplete thyroidectomy (HR 2.58, 95% CI 1.20-5.56) predicted worse DSS. Composite FTC/ATC tumors have survival outcomes that fall between those of FTC and ATC. Total thyroidectomy is a key component of treatment, as incomplete thyroidectomy is linked to poorer survival. Further research is needed to explore how the proportion of ATC within composite tumors influences survival outcomes.

PD-L1/PD-1 Expression in the Treatment of Oral Squamous Cell Carcinoma and Oral Potentially Malignant Disorders: An Overview of Reviews

Objective: In this overview, we present compelling evidence from multiple systematic reviews and meta-analyses (SRMAs) and examine the prognostic role of the PD-L1/PD-1 axis, as well as the potential of personalized treatment strategies targeting this axis, in patients with oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs). Methods: Six databases were searched to retrieve systematic review and meta-analysis studies. The population of interest was patients with OSCC and OPMDs in whom the expression of PD-L1 and PD-1 had been investigated. At least one of the following outcomes was reported, along with at least one clinicopathological feature: overall survival, disease-free survival, or disease-specific survival. All studies were assessed for risk of bias using the AMSTAR 2 tool. Results: A total of 195 studies were found through the initial search, and after duplicate removal, 97 studies were screened by title and abstract. Finally, five systematic reviews and meta-analysis studies fit our inclusion criteria and were included in this review. Conclusions: Based on two published systematic reviews, our study revealed a lack of evidence for the prognostic value of PD-L1 in improving overall survival in oral cancer patients. However, it showed a correlation with specific clinicopathological features such as sex, lymph node metastasis, and HPV status.

Lung Cancer Survival Period Prediction: Exploring Machine Learning Approaches

Lung cancer imposes the highest disease burden among all cancers and has the highest expected mortality rate, with 1.8 million deaths annually. It also has the lowest five-year survival rate, averaging at 20% among all diagnosed cancers. Machine learning (ML) offers a novel approach that has been utilized in healthcare for early detection, treatment planning, and survival time estimation. In this study, we applied various supervised, ensemble, and unsupervised ML algorithms to surveillance, epidemiology, and end results (SEER) lung cancer data to predict disease-specific survival (DSS) at 0.5-year, one-year, three-year, and five-year intervals. Our results show that ML models were effective in predicting short-term survival outcomes, but their ability to predict three-year and five-year survival was suboptimal. The limited performance of the models to predict survival outcomes may be attributed to the class imbalance that inherently exists in lung cancer patients. It may also be an indication of limited capacity of the selected features to predict long-term survival. Among the models tested, logistic regression (LR) and XGBoost were most robust algorithms to predict survival outcomes using given features. K-nearest neighbour (K-NN) and deep neural network (DNN) showed relatively weak performance as compared to other models in survival prediction. Additionally, the study found that household income, a socioeconomic factor, was the most significant predictor of survival across all time intervals. These findings highlight the potential of ML in survival prediction, particularly in the short term for lung cancer. The study also emphasizes the importance of addressing socioeconomic disparities as part of public health strategies to improve lung cancer outcomes.

Tumor-Stroma Ratio in Head and Neck Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.

Tumor-stroma ratio (TSR) has been recognized as a significant prognostic factor in various cancers. This systematic review evaluates the role of TSR in head and neck squamous cell carcinoma (HNSCC) and its association with patient outcomes such as overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), and lymph node metastasis (LNM). A comprehensive search was conducted across Scopus, Embase, PubMed, and Web of Science. Nineteen studies were included. Data extraction and quality assessment were performed progressively, with meta-analyses. All studies assessed TSR using hematoxylin and eosin staining of tissue samples. The meta-analyses focused on the impact of TSR on OS, DFS, DSS, and LNM, providing pooled hazard ratios (HRs) and odds ratios (ORs) with corresponding confidence intervals (CIs). Meta-analysis revealed a significant association between TSR and OS (HR 1.99, 95% CI 1.71-2.32, p < 0.001), DFS (HR 2.07, 95% CI 1.80-2.39, p < 0.001), DSS (HR 2.33, 95% CI 1.95-2.78, p < 0.001), and LNM (OR 1.76, 95% CI 1.15-2.70, p = 0.01). Minimal to low heterogeneity was detected among studies, and no publication bias was observed. TSR can effectively identify high-risk patients, being a reliable prognostic marker that could be readily integrated into routine pathology practice for HNSCC.

Characterizing Adenoid Cystic Carcinoma of the Middle Ear-A Rare Entity.

To characterize patient demographics, tumor features, treatment patterns, and survival outcomes of adenoid cystic carcinoma of the middle ear. Retrospective review of the Surveillance, Epidemiology, and End Results Database of the National Cancer Institute for all cases of histopathologically confirmed adenoid cystic carcinoma of the middle ear as the primary location. Twenty-one patients with adenoid cystic carcinoma of the middle ear were identified. Patients had a median age of 61 years (range 16-86) and were more commonly female (57.1%) and Caucasian (85.7%). Tumors had a median size of 11 mm (range 5-22) with disease involvement most frequently locally (70%), followed by distant (20%), then regional disease (10%). Most underwent upfront surgery (85.7%) compared to radiation therapy (14.3%). Surgery was often followed by radiation. Five- and ten-year disease-specific survival remained stable at 67.3%. Demographics of middle ear adenoid cystic carcinoma reflect that of other primary locations, with a predilection for middle-aged and female patients. Tumors more often present with local involvement, though distant metastasis is not uncommon. Surgery, followed by radiation, appears to be the favored treatment modality and generally portends a good prognosis, despite involvement of a complicated anatomic location. Further research is necessary to better characterize the disease and define its optimal management.

Prognostic Significance of Immune and Stromal Components in Colorectal Cancer: Practical Tools for Routine Pathologic Assessment.

In colorectal cancer (CRC), the tumor microenvironment includes cancer-associated fibroblasts and a variety of immune cells, which are increasingly recognized for their prognostic significance. To evaluate the tumor microenvironment in CRC using methodologies applicable in routine pathologic practice. A comprehensive evaluation of the local immune response and tumor to stroma ratio (TSR) was performed in 930 CRC cases by thoroughly reviewing the whole hematoxylin-eosin (H&E) slides. Local immune responses were assessed using peritumoral inflammatory infiltration (Klintrup-Mäkinen and modified Klintrup-Mäkinen methods), intratumoral stromal tumor-infiltrating lymphocytes (TILs; International TILs Working Group system and deep stromal TIL system), and Crohn-like lymphoid reaction (CLR). In the multivariate analysis, age (>68 years), stage III-IV, microsatellite stability, signet ring cell/undifferentiated carcinoma, extramural venous invasion, high TSR (>50%), and CLR were independent prognostic factors for disease-specific survival. Excluding microsatellite stability, these factors also served as significant prognostic indicators for progression-free survival. Among the 4 methods for measuring local immune response, evaluating the proportion of TILs within the deepest intratumoral stroma was an independent predictor of progression-free survival. We suggest that evaluating CLR, TSR, and stromal TILs on hematoxylin-eosin-stained slides represent a practical and straightforward approach with significant prognostic value.

Impact of Surgical Resection After Induction Gemcitabine Plus S-1-Based Chemoradiotherapy in Patients with Locally Advanced Pancreatic Ductal Adenocarcinoma: A Focus on UR-LA Cases

Background: This study aimed to assess the safety and efficacy of gemcitabine plus S-1-based chemoradiotherapy (GS-CRT) among patients with locally advanced pancreatic ductal adenocarcinoma (PDAC), especially among those with unresectable locally advanced (UR-LA) cases. Methods: A total of 351 consecutive PDAC patients were enrolled and prognostic predictors of disease-specific survival (DSS) were identified. Results: The treatment completion rate was 98.9% and Grade 3 or higher adverse events occurred in 181 cases (51.6%). Among 319 re-evaluated patients, pancreatectomy was performed in 184 (57.7%). Based on resectability, the 5-year DSS rates for the entire cohort were 39.6% (R), 43.8% (BR-PV), 21.2% (BR-A) and 13.3% (UR-LA), while the predictors of DSS were performance status (PS), hemoglobin (Hb) level, celiac artery (CA) involvement of ≥180 degrees and JPS 8th T category. In the resected cases, the predictors of DSS were preoperative PS, preoperative CA19-9 level, preoperative JPS-T factor, degree of histological response and adjuvant chemotherapy. In UR-LA resected patients, preoperative prognostic nutritional index (PNI), absence of pathological venous invasion and adjuvant chemotherapy were predictors of DSS. Conclusions: Even though Grade 3 or higher adverse events were encountered in about half of the cases, they were uneventfully managed. Therefore, GS-CRT is safe and highly tolerable with potential to improve patients‘ prognosis. Preoperative PS, CA19-9 levels and histological response are important prognostic factors, as well as adjuvant therapy. In UR-LA patients, prognostic nutritional index (PNI) and adjuvant chemotherapy were important for curative intent surgery.

SurvDB: Systematic Identification of Potential Prognostic Biomarkers in 33 Cancer Types.

The identification of cancer prognostic biomarkers is crucial for predicting disease progression, optimizing personalized therapies, and improving patient survival. Molecular biomarkers are increasingly being identified for cancer prognosis estimation. However, existing studies and databases often focus on single-type molecular biomarkers, deficient in comprehensive multi-omics data integration, which constrains the comprehensive exploration of biomarkers and underlying mechanisms. To fill this gap, we conducted a systematic prognostic analysis using over 10,000 samples across 33 cancer types from The Cancer Genome Atlas (TCGA). Our study integrated nine types of molecular biomarker-related data: single-nucleotide polymorphism (SNP), copy number variation (CNV), alternative splicing (AS), alternative polyadenylation (APA), coding gene expression, DNA methylation, lncRNA expression, miRNA expression, and protein expression. Using log-rank tests, univariate Cox regression (uni-Cox), and multivariate Cox regression (multi-Cox), we evaluated potential biomarkers associated with four clinical outcome endpoints: overall survival (OS), disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI). As a result, we identified 4,498,523 molecular biomarkers significantly associated with cancer prognosis. Finally, we developed SurvDB, an interactive online database for data retrieval, visualization, and download, providing a comprehensive resource for biomarker discovery and precision oncology research.

PRSS53 is a potential novel biomarker related to prognosis and immunity in clear cell renal cell carcinoma

ObjectiveTo analyze the expression levels, clinical significance, Immune infiltration and prognostic value of PRSS53 (Protease Serine 53) in clear cell renal cell carcinoma (ccRCC) using bioinformatics methods.MethodsData on PRSS53 in ccRCC were extracted from databases and platforms, including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), The Gene Expression Omnibus (GEO), Xiantao Academic Tool, Human Protein Atlas (HPA) and so on. We analyzed the relationship between PRSS53 expression and the clinical and pathological characteristics, diagnosis, immune infiltration and prognosis in ccRCC patients. Additionally, immunohistochemical analysis was performed on 9 pairs of ccRCC patient samples.ResultsPRSS53 was significantly upregulated in ccRCC and was closely associated with the TNM stage and histological grade of ccRCC. Receiver operating characteristic (ROC) curve analysis demonstrated the excellent diagnostic performance of PRSS53 in ccRCC (AUC = 0.928). Patients with high PRSS53 expression exhibited lower overall survival (OS) and disease-specific survival (DSS). Gene set enrichment analysis (GSEA) revealed that PRSS53 is involved in cellular functions such as anchored component of membrane, basement membrane and RNA-binding involved in post-transcriptional gene silencing. Single-sample GSEA (ssGSEA) indicated a positive correlation between PRSS53 expression and T helper cells infiltration levels, and a negative correlation with T gamma delta (Tgd) cell infiltration. PRSS53 was predominantly expressed in renal proximal tubules. The immunohistochemical results and HPA database showed that PRSS53 protein expression was significantly lower in clinical ccRCC tissues compared to normal tissues.ConclusionPRSS53 is a new prognostic biomarker and potential therapeutic target for ccRCC.

Prognostic factors and clinical significance of preoperative systemic therapy in patients with borderline resectable hepatocellular carcinoma: A JSHBPS project study 2023, Part 2.

To explore factors influencing the prognosis in patients with borderline-resectable hepatocellular carcinoma (BR-HCC) undergoing surgery. The clinical data of patients with BR-HCC according to the definition in the Expert Consensus Statement 2023 were collected from board-certified HPB training centers and analyzed in detail. Data of a total of 1509 patients with BR-HCC (BR1, n = 718 and BR2, n = 791) who underwent surgery were collected. The 5-year disease-specific survival rate (DSS) and 3-year recurrence-free survival rate (RFS) were determined as 40.8% and 19.7%, respectively. Multivariate analysis identified the oncological resectability category (i.e., BR2 vs. BR1) as a significant prognostic factor, and also the number of criteria fulfilled for classification into BR2 disease as being predictive of the DSS (hazard ratio (HR) [95% CI]: one factor: 1.32 [1.13-1.54]; two to three factors: 1.51 [1.15-1.96]). Preceding systemic therapy was significantly correlated with a longer DSS (HR, 0.41: 95% CI, 0.18-0.91) and RFS (HR, 0.80: 95% CI, 0.66-0.97) in the patients with BR1 disease, while its clinical significance was unclear in the patients with BR2 disease. Multicenter data confirm the clinical relevance of the oncological resectability category and the potential advantage of preceding systemic therapy in a specific group of BR-HCC.

RAC1 promotes the occurrence and development of tongue squamous cell carcinoma by regulating RAC1/PAK1/LIMK1 signaling pathway

Tongue squamous cell carcinoma (TSCC) remains an unsolved medical problem due to its poor local recurrence rate and prognosis. The purpose of this study was to investigate the expression characteristics of RAC-related C3 botulinum toxin substrate 1(RAC1) in TSCCS and its role in tumor invasion and metastasis. In this study, immunohistochemical staining was used to detect RAC1 expression in 150 tongue cancer specimens. The correlation between RAC1 and clinical-pathological characteristics is analyzed, along with the association between protein levels and disease-specific survival, metastasis-free survival, and local recurrence-free survival. In vitro experiments, RAC1 was knocked down by short hairpin RNA transfection to reveal the role of RAC1 in the invasion and metastasis of TSCC. The regulatory effects of RAC1 on CAL27 cell migration and invasion were evaluated by scratch and invasion methods. The influence of RAC1 expression on tumor growth was scrutinized using a subcutaneous transplant model in nude mice. RAC1 is overexpressed in TSCC and positively correlates with tumor invasion and metastasis. Moreover, elevated RAC1 expression is associated with poorer differentiation. Survival analysis further indicates that high expression of RAC1 is linked to increased recurrence and metastasis rates, as well as poorer prognosis. Additionally, both in vivo and in vitro studies demonstrate that RAC1 may impact tumor progression by modulating the epithelial–mesenchymal transition process through the RAC1/PAK1/LIMK1 signaling pathways. RAC1 overexpression is closely related to the progression of TSCC, and may provide a new prognostic indicator and therapeutic target for tongue cancer.

Necessity of selective neck dissection for T1-2N0 TSCC patients: a retrospective cohort study

BackgroundThis study aimed to assess the prognosis of T1-2N0 stage tongue cancer patients who underwent surgery for the primary lesion without elective neck dissection and to identify the risk factors for prognosis.MethodsWe retrospectively analyzed early-stage tongue cancer patients in our center. Statistical analyses were performed using SPSS and R software.ResultsThe study reviewed 168 patients, revealing a 3-year overall survival rate of 90.5%, a 3-year cervical lymph node metastasis-free survival rate of 73.2%, and a 3-year disease-specific survival rate of 89.3%. A depth of invasion of 3 mm showed significant prognostic value for overall survival (P = 0.001), cervical lymph node metastasis-free survival (P = 0.002), and disease-specific survival (P < 0.001). Patients were categorized into four subgroups (thick T1, thin T1, thick T2, and thin T2) to further explore the prognostic significance of depth of invasion across different T stage categories. The combination of T stage and a 3 mm depth of invasion demonstrated significant prognostic value in univariate analysis for overall survival (P = 0.002), cervical lymph node metastasis-free survival (P = 0.010), and disease-specific survival (P < 0.001). COX regression analysis confirmed the statistical significance of T stage combined with a 3 mm depth of invasion for overall survival (OR = 10.653; 95% CI, 2.394 to 47.404; P = 0.002) and lymph node metastasis-free survival (OR = 3.016; 95% CI, 1.365 to 6.667; P = 0.006).ConclusionsThe findings highlight depth of invasion and T stage as key prognostic factors in early-stage tongue squamous cell carcinoma. Consideration of elective neck dissection is advised for patients with T2 tumors and a depth of invasion exceeding 3 mm to potentially enhance their prognosis.Trial registrationThe current research was registered in Chinese Clinical Trial Registry on April 8, 2021. The trial registration number is ChiCTR2100045188.

Mesothelin (MSLN) is Highly Expressed in Triple Negative Breast Cancer and is Associated with Enhanced Cell Proliferation and Proinflammatory Tumor Microenvironment.

Mesothelin (MSLN), a cell surface glycoprotein, is commonly expressed in several cancers, including 40% of triple negative breast cancer (TNBC) cases. Although its cellular or physiologic functions remain unclear, MSLN has been leveraged as a target for molecular therapies. This study investigates MSLN's potential role in TNBC, the breast cancer (BC) subtype with poorest outcomes. The breast cancer (BC) cohorts from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC, n = 313), The Cancer Genome Atlas (TCGA, n = 160), and SCAN-B (n = 155) were used to obtain biological variables and gene expression data. High MSLN expression was primarily observed in epithelial cells, and its expression was associated with reduced stromal adipocytes in the tumor microenvironment (TME), supporting its role as a TNBC surface marker. MSLN expression was also associated with the TNBC subtype and advanced N stages in BC. However, MSLN expression did not correlate with long-term survival outcomes, including overall survival (OS), disease-specific survival (DSS), or disease-free survival (DFS); nevertheless, it was still associated with favorable response to neoadjuvant chemotherapy (NAC). Indeed, MSLN-high tumors exhibited a proinflammatory microenvironment, higher cancer-testis antigen (CTA) scores, and increased immune cell activity, notably immature dendritic cells (iDCs) and M1 macrophages. Biologically, MSLN expression was linked to increased cellular proliferation, with gene set enrichment analysis (GSEA) showing enrichment in pathways related to rapid proliferation, such as G2M checkpoint and E2F targets. MSLN-high TNBC is characterized by increased tumor grade, enhanced cell proliferation, and a proinflammatory microenvironment, showing better response to neoadjuvant chemotherapy without significant impact on long-term survival outcomes.

Development and validation of a dynamic prognostic nomogram for conditional survival in hepatocellular carcinoma: an analysis from the Korea Liver Cancer Registry

Compared to overall survival, conditional survival is a more relevant measure of prognosis in surviving patients over time. This study developed and validated a nomogram-based dynamic prognostic model to predict the conditional survival estimates of patients with hepatocellular carcinoma (HCC) through an analysis of a nationwide cancer registry. This retrospective cohort study included 2492 patients with HCC registered in the Korea Liver Cancer Registry. Patients underwent hepatic resection (HR) from 2008 to 2017, were followed up until December 2019, and were divided into development and validation cohorts. Univariate and multivariate Cox regression analyses were conducted to determine the risk factors for conditional survival of patients who underwent HR. The patients were scored based on the Cox regression coefficients; the nomogram was predicted by calculating the survival probability with Cox model. Our dynamic prognostic model nomogram for predicting conditional overall survival demonstrated Harrell’s C-index of 0.622 and 0.674 in the development and validation sets; for conditional disease-specific survival, it was 0.623 and 0.686 in the development and validation sets. The prediction power of the model is applicable in clinical practice. Factors incorporated in our nomogram included age, albumin, the ADV score, lymph node metastasis, and T stage in American Joint Commission on Cancer staging system. We developed and validated a nomogram to predict conditional survival estimates for overall survival and disease-specific survival. The proposed nomogram incorporating the ADV score presents a more accurate and useful prognostic prediction for patients with HCC who received HR.

Evaluation of the Apoptotic, Prooxidative and Therapeutic Effects of Odoroside A on Lung Cancer: An In Vitro Study Extended with In Silico Analyses of Human Lung Cancer Datasets.

The apoptotic effects of odoroside A on lung cancer cells were studied in our project. We also supported and extended our experimentally-proven results via bioinformatics analysis on human lung cancer tissues. In vitro studies were conducted using the A549 cell line. Cell proliferation was evaluated through a CCK-8 assay. For gene expression analysis, the qRT-PCR method was used, while CASP3 protein levels were detected using Western blotting and ELISA. Moreover, the oxidant status of cells was determined by measuring TAS and TOS levels. To construct a protein-protein interaction network, STRING analysis was performed. For the determination of differential expression of apoptosis-related genes, the GEPIA tool was utilized. Kaplan-Meier plots with overall survival, disease-specific survival and progression free intervals were obtained from UCSC Xena to evaluate the prognostic value of caspases. The gene expression levels of CASP3, CASP7, CASP8, CASP9, FAS, and FADD were elevated between 4-16 fold in Odo A-treated lung cancer cells compared to controls. CASP3 protein expression was significantly higher in Odo A-treated cancerous cells than the control group. Low TAS (0.5700 ± 0.0067 in Odo A vs. 0.6437 ± 0.0151 in control) and high TOS (0.82800 ± 0.0208 in Odo A vs. 0.6263 ± 0.0258 in control) levels as well as high OSI values (1.4531 ± 0.0414 in Odo A vs. 0.9748 ± 0.0539 in control) were obtained. Correlogram and protein-protein network analyses suggested strong correlations and interactions among target genes. Lastly, Kaplan-Meier analysis showed no prognostic value of caspases, but potential therapeutic targets in lung cancer. Anti-cancer, prooxidative and therapeutic effects of Odo A on lung cancer cells were shown in our study. These data were supported and extended via computational analyses that we performed. In conclusion, Odo A could be used in clinics to treat patients with lung cancer.

BUB1 serves as a biomarker for poor prognosis in liver hepatocellular carcinoma

BackgroundHepatocellular carcinoma (HCC) is the most frequent kind of liver cancer with high morbidity and mortality rates worldwide. Altered expression of BUB1 (budding uninhibited by benzimidazole 1) gene leads to chromosome instability and aneuploidy. This study investigated the expression of BUB1 and its prognostic value as well as its correlation with immune cell infiltration and immune checkpoints in HCC.ResultsUsing the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases, we found that BUB1 was up-regulated in HCC, thus prompting us to validate this observation by immunohistochemistry on 57 HCC paraffin embedded tissues from Wuxi No.2 People’s Hospital. Kaplan-Meier survival analysis revealed that HCC patients with high BUB1 expression had shorter overall survival (OS) time as well as progression-free interval (PFI), and disease-specific survival (DSS) time compared to the patients with low BUB1 expression. Besides, STRING database showed that the top 10 co-expression genes were mainly involved in the regulation of cell division during the mitosis. Gene Ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that BUB1 had a connection to cancer related pathways. Lastly, The Tumor Immune Estimation Resource (TIMER) analysis found that BUB1 was positively related to immune cell infiltration and some immune checkpoint gene in HCC.Clinical trial numberNot applicable.ConclusionsOur present study demonstrated that BUB1 is a potential prognostic biomarker, and BUB1 may play a role in the tumor immune microenvironment in HCC.Graphical

Predictive significance of microcystic elongated and fragmented (MELF) growth pattern in the prognosis of no specific molecular profile endometrial endometrioid carcinoma

Objective: To investigate the association between the microcystic, elongated, and fragmented (MELF) growth pattern and the prognosis of no specific molecular profile endometrial endometrioid carcinoma (NSMP-EEC). Methods: A retrospective study was conducted on 911 NSMP-EEC patients diagnosed at the Pathology Department of Peking University Third Hospital from January 2015 to September 2023. Complete hysterectomy specimens were obtained from these patients. Utilizing sanger sequencing, next generation sequencing and immunohistochemical techniques, we conducted endometrial carcinoma molecular classification according to WHO 2020 criteria, and identified clinical staging based on the International Federation of Gynecology and Obstetrics (FIGO) 2023 criteria. The primary endpoints were progression-free survival and disease-specific survival. Patients were divided into MELF (+) and MELF (-) groups based on the presence or absence of the MELF growth pattern, and clinicopathological characteristics were compared between the two groups. Kaplan-Meier survival curves were used to analyze the association between the MELF growth pattern and prognosis, and log-rank tests were performed to compare differences between groups. Results: The age of the 911 patients was (54.4±10.7) years, with a follow-up time [M (Q1,Q3)] of 24.0 (11.0, 41.0) months, and of which 147 patients (16.1%) belonged to the MELF (+) group. The MELF (+) group had a higher proportion of postmenopausal patients and G1/G2, deep myometrial invasion, lymphovascular space invasion, and lymph node metastasis, higher FIGO stages, higher ESGO risk groups, and higher tumor recurrence rates compared to the MELF (-) group (all P<0.05). The cumulative 5-year progression-free survival rate for MELF (-) and MELF (+) patients were 92.2% and 85.8%, respectively (P=0.015). In the G1/G2 NSMP-EEC cohort, the cumulative 5-year progression-free survival rate for MELF (-) and MELF (+) patients were 94.2% and 86.6%, respectively (P=0.003). The prognosis of NSMP-EEC patients with 2023 FIGO stage I was better, exhibiting a cumulative 5-year progression-free survival rate of 95.2% and a cumulative 5-year disease-specific survival rate of 99.1%, respectively, and MELF (+) was not associated with a decrease in either the cumulative progression-free survival rate (P=0.213) or the cumulative disease-specific survival rate (P=0.373) of patients. Conclusions: In NSMP-EEC patients, MELF (+) is associated with various adverse clinicopathological indicators and increased recurrence risk, providing a simple and rapid morphological indicator for risk stratification. The prognosis of NSMP-EEC patients with 2023 FIGO stage Ⅰis better, and the use of MELF alone is insufficient for risk stratification.

A Proposal for a Modified Evaluation System of Tumor-Infiltrating Lymphocytes Using HE-Stained Sections in Breast Cancer.

Tumor-infiltrating lymphocyte (TIL) scoring in tumor specimens has gained increasing attention in determining patients who are likely to benefit from immunotherapies. However, the histological evaluation methods of TILs in breast cancer remain limited. This study aimed to assess four components of lymphocytic reaction and overall lymphocytic score (L-score) used in colorectal cancer, investigate its association with clinicopathological factors, and examine the effect of TILs on postoperative mortality using 231 invasive breast cancers without neoadjuvant chemotherapy. Besides L-score, increasing modified L-score lacking peritumoral lymphocytic reaction was significantly associated with aggressive breast cancer phenotypes, including larger invasive size, higher tumor stage, higher Ki-67 labeling index, triple negative and HER2-enriched subtypes, and higher Nottingham histological grade. Importantly, modified L-score status but not L-score or TIL-Working Group (WG) score status was positively correlated with the disease-specific survival rate of the overall patients as well as the patients with luminal type or histological Grade III breast cancers. These results indicated that the modified L-score is a favorable method to comprehensively assess lymphocytic reaction to predict prognosis among patients with breast cancer, even compared with the currently used TIL-WG method, which may possess their potential integration into clinical practice.