Risk Factor For Overall Survival Research Articles

Integrating machine learning and multi-omics analysis to develop an immune-derived multiple programmed cell death signature for predicting clinical outcomes in gastric cancer

Abstract Objectives Metastasis of tumor cells is the leading reason for mortality among patients diagnosed with gastric cancer (GC). Emerging evidence indicated a strong correlation between programmed cell death (PCD) and the invasion and metastasis of tumor cells. Therefore, we aimed to develop a programmed cell death signature to assess the prognosis and therapeutic efficacy in GC patients. Methods Here, we collected 1911 PCD-related genes from 19 different PCD patterns, and developed an immune-derived multiple programmed cell death index (MPCDI) using the integrating machine learning and multi-omics analysis, and systematically dissected heterogeneity in GC patients. Subsequently, we divided GC patients into two categories, namely high-MPCDI group and low-MPCDI group, using the median MPCDI as the threshold. We performed a comprehensive analysis of the clinical characteristics, somatic mutations, immune infiltration, drug sensitivity, and immunotherapeutic efficacy of the two groups. Results Survival and immunotherapy response analyses indicated that the high-MPCDI patients experienced a poorer overall survival (p=0.018) and were more resistant to commonly used chemotherapeutic drugs but benefited from immunotherapy compared to the low-MPCDI patients. In addition, MPCDI was confirmed as a standalone risk factor for overall survival, and nomograms can provide a precise tool for the clinical diagnosis of GC patients. Conclusions Taken together, the MPCDI can serve as a robust clinical diagnostic classifier to guide medication administration and improve outcomes in GC patients.

203. THE NUMBER OF RESECTED LYMPH NODES FROM THE UPPER MEDIASTINAL AREA PREDICTS LONG-TERM OUTCOMES OF ESOPHAGEAL CANCER AFTER MIE

Abstract Background The total number of resected lymph nodes (LNs) is an important determinant of longer survival after esophagectomy for esophageal squamous cell carcinoma (ESCC). However, resected LN counts from which areas affect long-term outcomes remain unclear. Methods: This study comprised 406 patients who underwent minimally invasive esophagectomy (MIE) at Kobe University Hospital. Resected LN counts were evaluated in the following areas: upper mediastinal (UM), middle mediastinal (MM), lower mediastinal (LM), and abdominal (Abd). Cut-off values for LN counts from each area were determined using receiver operating characteristics analysis to the survival status. Cox proportional hazards regression analyses were performed to identify prognostic factors. Results: The cut-off values for large or small numbers of resected LN counts in the UM, MM, LM, and Abd areas were 4, 8, 5, and 18 in patients with upper and middle thoracic (Ut/Mt) ESCC, respectively, and 7, 6, 5, and 24 in patients with lower thoracic (Lt) ESCC, respectively. Multivariate analysis in patients with Ut/Mt ESCC revealed that tumor invasion depth, lymph node metastasis and the resected LN count from the UM area were independent risk factors for overall survival (hazard ratio = 7.04; 95% confidence interval = 4.47-11.1, hazard ratio = 4.01; 95% confidence interval = 1.96-8.21, hazard ratio = 2.18; 95% confidence interval = 1.24-3.82, respectively). In patients with Lt ESCC, tumor invasion depth, lymph node metastasis and pulmonary complication were independent risk factors for overall survival (hazard ratio = 4.23; 95% confidence interval = 2.14-8.35, hazard ratio = 3.83; 95% confidence interval = 1.75-8.38, hazard ratio = 2.80; 95% confidence interval = 1.38-5.65, respectively). Resected LN counts from no areas were prognostic factors. Conclusions: The number of resected LNs from the UM area influenced survival outcomes of patients with Ut/Mt ESCC after MIE.

Preoperative Prognostic Stratification and Prediction of Long-term Outcomes after Pancreatoduodenectomy for Distal Cholangiocarcinoma

BackgroundPatients with distal cholangiocarcinoma (DCC) frequently receive adjuvant chemotherapy in preoperative and postoperative settings, but prediction of prognostic risk at the time of treatment selection remains challenging. MethodsThis single-center retrospective study enrolled DCC patients who underwent initial pancreatoduodenectomy (PD) between 2009 and 2022. Preoperative clinical parameters were collected, and Cox regression analysis was used to identify risk factors for overall survival (OS). ResultsAmong 170 patients examined, the median tumor depth was 10 mm, and 37% of the patients were diagnosed with pT3. Overall, 46% of patients had lymph node metastasis. The median and 5-year OS was 58.2 months and 50%, respectively. Multivariate analysis revealed tumor size on computed tomography (CT) ≥15 mm and main pancreatic duct (MPD) dilatation (≥3 mm) as independent risk factors for OS among various preoperative parameters; the prognosis was stratified based on these two parameters. Patients with one risk factor had similar outcomes (5-year OS: 39%) to pStage IIB DCC (pT2N1 or pT3), while those with two risk factors had a prognosis akin to pStage IIIA (pN2), with a high early recurrence rate of 64% (5-year OS: 8%). Among non-risk group patients with low carbohydrate antigen (CA)19-9 levels (<37 U/mL), the prognosis was comparable (5-year OS: 72%) to those with pStage I DCC. ConclusionA simple stratification approach was developed to predict long-term postoperative outcomes. To improve poor prognosis, intensive therapy, including neoadjuvant chemotherapy, should be considered for patients with two risk factors.

Integrated machine learning survival framework to decipher diverse cell death patterns for predicting prognosis in lung adenocarcinoma.

Various forms of programmed cell death (PCD) collectively regulate the occurrence, development and metastasis of tumors. Nevertheless, a comprehensive analysis of the diverse types of PCD in lung adenocarcinoma (LUAD) is currently lacking. The study encompassed a total of 1481 genes associated with the regulation of 13 distinct PCD patterns. Ten machine learning algorithms were amalgamated into 101 combinations, from which the optimal algorithm was chosen to formulate an artificial intelligence-derived prognostic signature based on the average C-index across four multicenter cohorts. The established optimal cell death index (CDI) model emerged as an independent risk factor for overall survival, demonstrating robust and consistent performance. Notably, CDI exhibited significantly higher accuracy compared to traditional clinical variables and molecular features. It exhibited superior performance than other published models. By integrating CDI with relevant clinical features, a nomogram with excellent predictive performance was developed. LUAD patients with low CDI score had a higher immune modulators, TIDE scores and immune scores, indicating a better immunotherapy benefit. More importantly, we found that the regulation of antigen presentation is the crucial mechanism of PCD. SCG2 is a key molecule that inhibits the malignant progression of LUAD. CDI holds great potential as a robust and promising tool for enhancing clinical outcomes in patients with LUAD.

Comparison between AWGC-cachexia and GLIM-malnutrition in patients with gastric cancer

BackgroundThe newly released Asian Working Group for Cachexia (AWGC) criteria share similar diagnostic items with the Global Leadership Initiative on Malnutrition (GLIM) criteria. This study aims to compare the AWGC cachexia and GLIM malnutrition in patients with gastric cancer and investigate whether one diagnosis continues to be a prognostic factor in individuals diagnosed with the other condition. MethodsData of patients who underwent radical gastrectomy for gastric adenocarcinoma were prospectively collected from 2013 to 2019. The AWGC and GLIM criteria were applied to diagnosis cachexia and malnutrition, respectively. Univariate and multivariate logistic and Cox regression were used to verify the effect of relevant factors on postoperative complications and overall survival. ResultsA total of 1420 patients were included, among whom 174 (12.3 %) were diagnosed with AWGC-cachexia alone, 85 (6.0 %) were diagnosed with GLIM-malnutrition alone, and 324 (22.8 %) had both AWGC-cachexia and GLIM-malnutrition. Both AWGC-cachexia and GLIM-malnutrition were independent risk factors for complications and overall survival. When they coexisted, the odds ratios (OR) and hazard ratios (HR) tended to be higher. In the AWGC-cachexia subset, GLIM-malnutrition remained an independent risk factor (HR = 1.544, 95 % CI = 1.098–2.171, P = 0.012) for overall survival after the adjustment of confounding factors. Similarly, in the GLIM-malnutrition subset, AWGC-cachexia remained an independent risk factor for overall survival (HR = 1.697, 95 % CI = 1.087–2.650, P = 0.020). Patients with both cachexia and malnutrition had the worst overall survival. ConclusionAWGC-cachexia and GLIM-malnutrition criteria were two non-redundancy tools in reflecting mortality risk in preoperative nutritional assessment.

The impact of uncertainty resection on the prognosis of non-small cell lung cancer

Objective: To explore the impact of uncertain resection on postoperative survival in non-small cell lung cancer. Methods: This is a retrospective cohort study. A retrospective analysis was conducted on the data of 477 patients with non-small cell lung cancer who underwent lobectomy in the Department of Thoracic Surgery, the Fourth Hospital of Hebei Medical University from December 2012 to December 2013. There were 302 males and 175 females, aged (59±8) years (range: 27 to 79 years). According to the surgical resection criteria issued by the International Association for the Study of Lung Cancer, the patients were divided into the intact resection group (R0 group, 286 cases) and the uncertain resection group (R (un) group, 191 cases). Clinical data between the two groups were compared using χ2 test, and propensity score matching (PSM) was performed on patients using the R language, with matching variables including gender, age, smoking history, adjuvant therapy, TNM stage, pathological type, and tumor site. The nearest-neighbor method was used for 1∶3 matching and the caliper value was 0.02. The survival curve was plotted using the Kaplan-Meier method and compared using the Log-rank test. The Cox proportional hazards regression model was used to identify risk factors in overall survival (OS). Subgroup analysis was based on TNM staging and mediastinal lymph node metastasis status. Results: In the R (un) group, 68 patients had positive lymph in the highest group and 129 patients did not undergo complete dissection of the mediastinal lymph nodes. The baseline data for the R0 group and the R (un) group were corrected using PSM, and a total of 369 patients were successfully matched, including 227 cases in the R0 group and 142 cases in the R (un) group. After PSM, the 5-year survival rates of the R0 group and the R (un) group were 64.3% and 52.1%, respectively (P=0.021). The 5-year survival rates of stage Ⅰ, Ⅱ, and Ⅲ patients were 85.2%, 65.9%, and 34.8%, respectively (P<0.01). TNM stage (χ2=46.913, P<0.01), pathological classification of adenosquamous cell carcinoma (HR=5.970, 95% CI: 3.117 to 11.431, P<0.01) and R (un) resection (HR=1.512, 95% CI: 1.065 to 2.147, P=0.021) were prognostic factors for postoperative survival. Subgroup analysis showed that in stage Ⅲ patients, 5-year survival rates of the R0 group and the R (un) group after resection were 45.8% and 9.5%, respectively (P=0.002). Among patients with mediastinal lymph node metastasis, 5-year survival rates of the R0 group and the R (un) group were 50.6% and 7.1%, respectively (P<0.01). Conclusions: TNM staging, pathological type, and R (un) resection are prognostic factors for overall postoperative survival in non-small cell lung cancer. In stage Ⅰ and Ⅱ patients, R (un) is not a prognostic factor for postoperative survival of non-small cell lung cancer. In patients with stage Ⅲ and mediastinal lymph node metastasis, R (un) is a prognostic factor for non-small cell lung cancer after surgery.

Correlation between tumor budding and the long-term follow-up outcomes after endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma.

The effect of tumor budding (TB) on the prognosis of patients with esophageal squamous cell carcinoma (ESCC) after endoscopic submucosal dissection (ESD) remains unclear. We evaluated the long-term outcomes of patients with superficial ESCC after ESD and the risk factors of TB for the long-term prognosis. We conducted a retrospective study in a Chinese hospital. All patients with ESCC treated by ESD and reported TB were included consecutively. Comparative analyses were conducted in three parts: specimen analysis, follow-up analyses of unmatched patients, and propensity score-matched (PSM) patients. Cox proportional hazard regression models were constructed to identify risk factors for overall survival and recurrence-free survival (RFS). A total of 437 patients were enrolled [154TB and 283 no tumor budding (NTB)], and 258 patients (52TB and 206 NTB) were included in the follow-up analysis. Results showed that the invasion depth, differentiation type, and positive vascular invasion (all p < 0.001) of the TB group were significantly different from the NTB group. The all-cause mortality and the median RFS time between the two groups were comparable. RFS rate at 5years were 84.6% and 80.6%, respectively (p = 0.43). Cox analyses identified that having other cancers but not TB, as a risk factor independently associated with overall survival and RFS after ESD. TB tends to be associated with invasion depth, differentiation type, and positive vascular invasion. However, it might not affect the long-term outcomes of patients with superficial ESCC after ESD when other high-risk factors are negative.

A novel T1a/b classification for testicular cancer: not only seminoma.

The 8th edition of the American Joint Committee on Cancer (AJCC) manual divides T1 stage testicular cancer into T1a and T1b, but it is only applicable to seminoma. The purpose of this observational study is to discuss further the possibility of extending this classification system to any T1 testicular cancer. Testicular cancer patients from 2000 to 2018 in the Surveillance, Epidemiology, and End Results (SEER) database were included in this analysis. After patient selection, univariate and multivariate Cox regression were used to evaluate the impact of tumor size on survival in patients with T1 testicular cancer. A time-dependent receiver operation curve (ROC) was used to determine the best tumor size cut-off value for further T1 subgroup classification. Restricted cubic splines (RCS) analysis was used to compare different tumor sizes with the best tumor size cut-off value. Propensity score matching (PSM) analysis was conducted to generate baseline balanced data to validate findings. A total of 6,630 patients were included in this study. In the Cox regression model, we found that T1b staged tumor (>34 mm) was an independent risk factor of overall survival [OS, adjusted hazard ratio (HR): 1.57, 95% confidence interval (CI): 1.12-2.21] and cancer-specific survival (CSS, adjusted HR: 5.027, 95% CI: 1.95-12.93). Further PSM analysis consolidated our results. For any T1 testicular cancer, a tumor size of 34 mm could be used as the demarcation point to assess the prognosis. Adopting personalized treatments and follow-up plans may help improve the OS and CSS rate for testicular cancer patients.

Interim efficacy of a multicenter cohort study for China Net Childhood Lymphoma mature B-cell lymphoma 2017 regimen in the treatment of pediatric High-grade-B cell lymphoma

Objective: To analyze the mid-term efficacy of the China Net Childhood Lymphoma mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen in treating children with high-grade B-cell lymphoma (HGBL). Methods: Clinical and pathological data of HGBL children aged≤18 years admitted to 16 hospitals of the Chinese Children's Lymphoma Collaborative Group (CNCL) from May 2017 to April 2021 were collected retrospectively. They were divided in to high-grade B-cell lymphoma with double hit/triple hit (HGBL-DH/TH) group and high-grade B-cell lymphoma non-specified (HGBL-NOS) group, according to the 2016 version of the World Health Organization (WHO) Hematopoietic and Lymphoid Tissues Cancer Classification. Both groups of patients were treated with stratified chemotherapy by risk according to the CNCL-B-NHL-2017 scheme. The deadline for follow-up was December 31, 2023. All the patients were examined by chromosome fluorescence in situ hybridization (FISH), and the rearrangement of genes MYC, BCL-2 and BCL-6 was confirmed. The clinical and pathological characteristics of patients at disease onset were analyzed, and the therapeutic effects of patients in different clinical stages and risk groups were compared. Survival analysis was drawn by Kaplan Meier method, the log-rank test was used to compare the differences in the cumulative survival rate between different groups, and multivariate Cox regression model was used to identify the prognostic factors. Results: A total of 62 patients were included, with an onset age [M(Q1, Q3)] of 7 (4, 11) years, including 48 males and 14 females. There were 11 (17.7%) patients in stageⅡ, 33(53.2%)patients in stage Ⅲ and 18(29.1%)patients in stage Ⅳ. FISH testing showed that 4 cases (6.5%) were HGBL-DH and 3 (4.8%) were HGBL-TH. The remaining 55 cases (88.7%) were HGBL-NOS, with 18 cases accompanied by MYC rearrangement. There were 7 cases in the HGBL-DH/TH group and 55 cases in the HGBL-NOS group. Thirteen cases (20.9%) were treated with the B1 regimen, 3 cases (4.8%) with B2 regimen, 37 cases (59.6%) with C1 regimen, and 9 cases (14.7%) with the C2 regimen. Forty-eight cases (77.4%) received rituximab therapy at the same time. Five cases (8.0%) progressed during treatment. The follow-up time [M(Q1, Q3)] was 43.5 (36.1, 53.7) months. The complete remission rate was 91.9% (57/62). The 3 year overall survival rate was 93.5% and event-free survival (EFS) rate was 91.9%. The 3-year overall survival rate in the HGBL-NOS group was higher than that in the HGBL-DH/TH group (96.3% vs 71.4%, P=0.011). The 3-year EFS rate of the HGBL-NOS group was higher than that of the HGBL-DH/TH group (94.5% vs 71.4%, P=0.037). In the HGBL-NOS subgroup, the overall survival rate of children with MYC rearrangement was lower (100% vs 88.9%,P=0.039). Multivariate Cox regression analysis showed that central invasion (HR=6.05, 95%CI: 1.96-38.13, P=0.046) was a risk factor for overall survival. Conclusion: CNCL-B-NHL-2017 regimen shows significant effects in the treatment of pediatric HGBL, with a good prognosis.

GATIS score for predicting the prognosis of rectal neuroendocrine neoplasms: A Chinese multicenter study of 12-year experience.

There is currently a shortage of accurate, efficient, and precise predictive instruments for rectal neuroendocrine neoplasms (NENs). To develop a predictive model for individuals with rectal NENs (R-NENs) using data from a large cohort. Data from patients with primary R-NENs were retrospectively collected from 17 large-scale referral medical centers in China. Random forest and Cox proportional hazard models were used to identify the risk factors for overall survival and progression-free survival, and two nomograms were constructed. A total of 1408 patients with R-NENs were included. Tumor grade, T stage, tumor size, age, and a prognostic nutritional index were important risk factors for prognosis. The GATIS score was calculated based on these five indicators. For overall survival prediction, the respective C-indexes in the training set were 0.915 (95% confidence interval: 0.866-0.964) for overall survival prediction and 0.908 (95% confidence interval: 0.872-0.944) for progression-free survival prediction. According to decision curve analysis, net benefit of the GATIS score was higher than that of a single factor. The time-dependent area under the receiver operating characteristic curve showed that the predictive power of the GATIS score was higher than that of the TNM stage and pathological grade at all time periods. The GATIS score had a good predictive effect on the prognosis of patients with R-NENs, with efficacy superior to that of the World Health Organization grade and TNM stage.

The combination of handgrip strength and CONUT predicts overall survival in patients with gastrointestinal cancer: A multicenter cohort study

BackgroundThe controlled nutritional status score (CONUT) and handgrip strength (HGS) were both predictive indexes for the prognosis of cancers. However, the combination of CONUT and HGS for predicting the prognosis of gastrointestinal cancer had not been developed. This study aimed to explore the combination of CONUT and HGS as the potential predictive prognosis in patients with gastric and colorectal cancer. MethodsA cohort study was conducted with gastric and colorectal cancer patients in multicenter in China. Based on the optimal HGS cutoff value for different sex, the HGS cutoff value was determined. The patients were divided into high and low HGS groups based on their HGS scores. A CONUT score of 4 or less was defined as a low CONUT, whereas scores higher than 4 were defined as high CONUT. The Kaplan-Meier method was used to create survival curves, and the log-rank test was used to compare time-event relationships between groups. A Cox proportional hazard regression model was used to determine independent risk factors for overall survival (OS). ResultsA total 2177 gastric and colorectal patients were enrolled in this study, in which 1391 (63.9%) were men (mean [SD] age, 66.11 [11.60] years). Multivariate analysis revealed that patients with high HGS had a lower risk of death than those with low HGS (hazard ratio [HR],0.87; 95% confidence interval [CI], 0.753-1.006, P=0.06), while high CONUT had a higher risk of death than those with low CONUT (HR, 1.476; 95% CI, 1.227-1.777, P< 0.001). Patients with both low HGS and high CONUT had 1.712 fold increased risk of death (HR, 1.712; 95% CI, 1.364-2.15, P < 0.001). Moreover, cancer type and sex were stratified and found that patients with high CONUT and low HGS had lower survival rate than those with low CONUT and high HGS in both gastric or colorectal cancer, and both male and female. ConclusionA combination of low HGS and high CONUT was associated with poor prognosis in patients with gastrointestinal cancer, which could probably predict the prognosis of gastrointestinal cancer more accurate than HGS or CONUT alone.

ELOVL1 is upregulated and promotes tumor growth in hepatocellular carcinoma through regulating PI3K-AKT-mTOR signaling

BackgroundThe functions of the ELOVLs are mainly involved in the elongation of saturated and polyunsaturated fatty acids, thus influencing the metabolism of fatty acids. Abnormal lipid metabolism may result in NAFLD and NASH, which may lead to cirrhosis and liver cancer. These results suggest that ELOVLs-mediated metabolism might be involved in the development of HCC. The purpose of this study was to study the expression and function of ELOVL1 in human liver cancer. MethodUsing TCGA, GEPIA and other databases, we analyzed the relationship between the expression of ELOVL1 and liver cancer. The expression of ELOVL1 was detected by immunohistochemical method and Western blot method in hepatic carcinoma and hepatic carcinoma cells. Then, the effects of ELOVL1 on proliferation, apoptosis and invasion in vitro and in vivo were investigated by means of different methods. ResultOur results indicate that ELOVL1 is more highly expressed in liver cancer than in normal tissues. Survival analysis showed that OS and DSS were shorter in patients with high ELOVL1 expression than in those with low expression. Multivariate Cox analysis further demonstrated that over-expression of ELOVL1 was an independent risk factor for overall survival in HCC. The results of ROC also confirmed the value of ELOVL1 in the diagnosis of liver cancer. The results of KEGG enrichment and GSEA indicate that ELOVL1 is associated with lipid metabolism and NAFLD, as well as PPAR, PI3K-AKT-mTOR. Compared with the control group, it was found that silencing ELOVL1 in Huh7 and HepG2 cells could inhibit the growth of cells, promote the apoptosis and decrease the metastasis and invasion. Changes in ELOVL1 induced cell proliferation and metastasis may be related to PI3K/AKT/mTOR. Low expression of ELOVL1 inhibited the growth of xenograft tumors in hepatocellular carcinoma xenograft model. ConclusionOur data indicate that the activation of PI3K/AKT/mTOR pathway in HCC may contribute to the promotion of cancer. Thus, ELOVL1 may be a promising therapeutic target for HCC.

The effect of BMI on survival outcome of breast cancer patients: a systematic review and meta-analysis.

The main goal of the present research is to explore the potential link of body mass index (BMI) with different survival metrics in breast cancer patients. Our aim is to offer the latest and most thorough meta-analysis, assessing the strength and reliability of the connection that BMI has with prognostic indicators in this disease. As of January 2024, we conducted a systematic literature search across PubMed, Embase, Web of Science, and the Cochrane Library databases. Our search aimed to identify studies examining BMI as an exposure factor, with breast cancer patients constituting the study population, and utilizing adjusted hazard ratio (HR) as the data type of interest. The evidence synthesis incorporated a total of 61 eligible articles involving 201,006 patients. Being underweight posed a risk factor for overall survival (OS) in breast cancer patients compared to normal weight (HR 1.15, 95% CI 0.98-1.35; P = 0.08). Overweight or obesity, in comparison to normal weight, was a risk factor for OS (HR 1.18, 95% CI 1.14-1.23; P < 0.00001), disease-free survival (DFS) (HR 1.11, 95% CI 1.08-1.13; P < 0.00001), relapse-free survival (RFS) (HR 1.14, 95% CI 1.06-1.22; P = 0.03), and breast cancer-specific survival (BCSS) (HR 1.18, 95% CI 1.11-1.26; P < 0.00001), but not for progression-free survival (PFS) (HR 0.91, 95% CI 0.76-1.10; P = 0.33). Notably, in subgroup analyses, overweight patients achieved prolonged PFS (HR 0.80, 95% CI 0.64-0.99; P = 0.04), and compared to the obese population, the overweight cohort exhibited a significant difference in OS (HR 1.11, 95% CI 1.05-1.16; P < 0.00001) and DFS (HR 1.06, 95% CI 1.03-1.10; P = 0.0004), with a considerably stronger association. Furthermore, compared to HER- patients, HER + patients exhibited a greater predictive value for OS (HR 1.23, 95% CI 1.10-1.37; P = 0.0004), RFS (HR 1.30, 95% CI 1.03-1.64; P < 0.00001), and DFS (HR 1.10, 95% CI 1.03-1.17; P = 0.003). The results of our meta-analysis reveal a notable association between BMI and various survival measures in breast cancer prognosis. These findings provide a solid basis for predicting breast cancer outcomes and implementing more effective therapeutic approaches.

Clinical Characteristics and Prognosis of Early-Onset Hepatocellular Carcinoma: A Retrospective Cohort Study Based on Population Data.

The incidence of young patients diagnosed with hepatocellular carcinoma (HCC) is projected to rise. This study aimed to investigate the distinctive characteristics of adolescent and young adult (AYA) patients with HCC and identify the risk factors that impact their survival. This study included 1005 AYA patients and 55,435 older adult (OA) patients with HCC, using data from the Surveillance, Epidemiology, and End Results database. Propensity score matching was used to adjust for baseline differences in patient characteristics. The Kaplan-Meier curve and log-rank test are utilized to compare the overall survival between the two groups. The Cox proportional hazards regression model was used for subgroup analysis to identify risk factors for overall survival in AYA patients. AYA patients exhibited a higher proportion of advanced clinical stage (49.15% vs 37.57%, P < 0.001) and fibrolamellar hepatocellular carcinoma (14.13% vs 0.09%, P < 0.001), but a lower incidence of alpha-fetoprotein positivity (32.04% vs 45.32%, P < 0.001) and cirrhosis (8.86% vs 18.32%, P < 0.001). The subgroup analysis results indicated that AYA patients had a more favorable prognosis than OA patients in most subgroups. Undifferentiated carcinoma emerged as the predominant risk factor for AYA patients (Hazard Ratio [HR], 6.08 [2.53-14.62]), whereas partial hepatectomy was determined to be the most advantageous factor (HR, 0.29 [0.23-0.37]). AYA patients with HCC exhibit more aggressive characteristics but demonstrate a better prognosis compared to the OA group, necessitating personalized surveillance and treatment.

A Simple Prognostic Scoring System for Hepatocellular Carcinoma Treated with DEB-TACE.

To develop a simple and effective prognostic scoring system to predict the efficacy of drug-eluting bead-transcatheter arterial chemoembolization (DEB-TACE) in the treatment of hepatocellular carcinoma (HCC). Data were retrospectively collected from 230 patients with HCC who received DEB-TACE treatment at six medical centers between January 2019 and December 2022. We developed a predictive score based on independent risk factors for overall survival (OS), validated the model using a validation cohort, and compared its prognostic accuracy with commonly used HCC staging systems. The number of tumors, albumin-bilirubin levels, alpha-fetoprotein levels, and portal vein thrombus grade were identified as independent factors influencing OS. Based on these factors, we established the DEB-TACE treatment of HCC (DTH) scoring system. The DTH score correlated well with OS, which decreased as the DTH score increased. According to the DTH score, patients were categorized into three risk groups: low-risk (DTH-A, 0-4 points), medium-risk (DTH-B, 5-6 points), and high-risk (DTH-A, 7 points). The OS of each risk group was 18.73±0.62 months, 12.73±0.10 months, and 6.93±0.19 months, respectively (p<0.001). The external cohort validation confirmed the accuracy of the DTH score, demonstrating superior predictive performance compared to other commonly used HCC scoring systems. The DTH-HCC scoring system effectively predicts the outcomes of HCC patients undergoing DEB-TACE as initial treatment. This model can aid in the initial planning and decision-making process for DEB-TACE treatment in HCC patients.

Multi-omics data analysis reveals the complex roles of age in differentiated thyroid cancer

AimsAge is a major risk factor for differentiated thyroid cancer (DTC); however, the mechanisms underlying aging-regulated progression of DTC remains unclear. MethodsBased on multi-omics data (transcriptional files, somatic mutation files, methylation files) derived from the TCGA database, we comprehensively investigated the genomic and biological features associated with aging in patients with DTC. ResultsWe confirmed that age was an independent risk factor for overall survival and progression-free survival of patients with DTC, and confirmed that 55 years of age (adopted in the 8th AJCC staging system) is an appropriate cutoff for patients with DTC rather than 45 years (adopted in the 7th AJCC staging system). Using 55 years as the cutoff, we demonstrated DNA methylation-driven transcriptional regulation during aging, and identified the landscape of somatic mutations in young and old patients with DTC along with two aging-related mutations: TTN and EIF1AX. Subsequently, we investigated the infiltration of immune cells in DTC, and found that old patients exhibited decreased CD8+ T cells infiltration with lower cytotoxicity. Finally, we constructed a prognosis prediction model based on three age-related genes (PTK2B, E2F1, and GHR) that showed satisfactory performance in predicting patients prognosis. ConclusionsWe comprehensively investigated the complex interplay between age and biological features of DTC, which may provide new insights into the role of aging in DTC.

Impact of pancreatic ductal occlusion on postoperative outcomes in pancreatic head cancer patients undergoing neoadjuvant therapy

BackgroundPancreatic ductal occlusion can accompany pancreatic head cancer, leading to pancreatic exocrine insufficiency (PEI) and adverse effects on nutritional status and postoperative outcomes. We investigated its impact on nutritional status, body composition, and postoperative outcomes in patients with pancreatic head cancer undergoing neoadjuvant therapy (NAT).MethodsWe analyzed 136 patients with pancreatic head cancer who underwent NAT prior to intended pancreaticoduodenectomy (PD) between 2015 and 2022. Nutritional and anthropometric indices (body mass index [BMI], albumin, prognostic nutritional index [PNI], Glasgow prognostic score, psoas muscle index, subcutaneous adipose tissue index [SATI], and visceral adipose tissue index) and postoperative outcomes were compared between the occlusion (n = 78) and non-occlusion (n = 58) groups, in which 61 and 44 patients, respectively, ultimately underwent PD.ResultsThe occlusion group showed significantly lower post-NAT BMI, PNI, and SATI (p = 0.011, 0.005, and 0.015, respectively) in the PD cohort. The occlusion group showed significantly larger main pancreatic duct, smaller pancreatic parenchyma, and greater duct–parenchymal ratio (p < 0.001), and these morphological parameters significantly correlating with post-NAT nutritional and anthropometric indices. Postoperative 3-year survival and recurrence-free survival (RFS) rates were significantly poorer (p = 0.004 and 0.013) with pancreatic ductal occlusion, also identified as an independent postoperative risk factor for overall survival (hazard ratio [HR]: 2.31, 95% confidence interval [CI] 1.08–4.94, p = 0.030) and RFS (HR: 2.03, 95% CI 1.10–3.72, p = 0.023), in multivariate analysis.ConclusionsPancreatic ductal occlusion may be linked to poorer postoperative outcomes due to PEI-related malnutrition.

Abdominal aortic calcification volume as a preoperative prognostic predictor for pancreatic cancer.

Atherosclerosis and cancer may progress through common pathological factors. This study was performed to investigate the association between the abdominal aortic calcification (AAC) volume and outcomes following surgical treatment for pancreatic cancer. The subjects of this retrospective study were 194 patients who underwent pancreatic cancer surgery between 2007 and 2020. The AAC volume was assessed through routine preoperative computed tomography. Univariate and multivariate analyses were performed to evaluate the impact of the AAC volume on oncological outcomes. A higher AAC volume (≥ 312 mm3) was identified in 66 (34%) patients, who were significantly older and had a higher prevalence of diabetes and sarcopenia. Univariate analysis revealed several risk factors for overall survival (OS), including male sex, an AAC volume ≥ 312 mm3, elevated carbohydrate antigen 19-9, prolonged operation time, increased intraoperative bleeding, lymph node metastasis, poor differentiation, and absence of adjuvant chemotherapy. Multivariate analysis identified an AAC volume ≥ 312 mm3, prolonged operation time, lymph node metastasis, poor differentiation, and absence of adjuvant chemotherapy as independent OS risk factors. The OS rate was significantly lower in the high AAC group than in the low AAC group. The AAC volume may serve as a preoperative prognostic indicator for patients with pancreatic cancer.

Prognostic value of the Naples prognostic score in patients with intrahepatic cholangiocarcinoma after hepatectomy

BackgroundThe Naples Prognostic Score (NPS), integrating inflammatory and nutritional biomarkers, has been reported to be associated with the prognosis of various malignancies, but there is no report on intrahepatic cholangiocarcinoma (ICC). This study aimed to explore the prognostic value of NPS in patients with ICC.MethodsPatients with ICC after hepatectomy were collected, and divided into three groups. The prognosis factors were determined by Cox regression analysis. Predictive efficacy was evaluated by the time-dependent receiver operating characteristic (ROC) curves.ResultsA total of 174 patients were included (Group 1: 33 (19.0%) patients; Group 2: 83 (47.7%) patients; and Group 3: 58 (33.3%) patients). The baseline characteristics showed the higher the NPS, the higher the proportion of patients with cirrhosis and Child-Pugh B, and more advanced tumors. The Kaplan-Meier curves reflect higher NPS were associated with poor survival. Multivariable analysis showed NPS was an independent risk factor of overall survival (NPS group 2 vs. 1: HR = 1.671, 95% CI: 1.022–3.027, p = 0.009; NPS group 3 vs. 1: HR = 2.208, 95% CI: 1.259–4.780, p = 0.007) and recurrence-free survival (NPS group 2 vs. 1: HR = 1.506, 95% CI: 1.184–3.498, p = 0.010; NPS group 3 vs. 1: HR = 2.141, 95% CI: 2.519–4.087, P = 0.001). The time ROC indicated NPS was superior to other models in predicting prognosis.ConclusionsNPS is a simple and effective tool for predicting the long-term survival of patients with ICC after hepatectomy. Patients with high NPS require close follow-up, and improving NPS may prolong the survival time.

Assessment of AURKA expression and prognosis prediction in lung adenocarcinoma using machine learning-based pathomics signature

ObjectiveThis study aimed to develop quantitative feature-based models from histopathological images to assess aurora kinase A (AURKA) expression and predict the prognosis of patients with lung adenocarcinoma (LUAD). MethodsA dataset of patients with LUAD was derived from the cancer genome atlas (TCGA) with information on clinical characteristics, RNA sequencing and histopathological images. The TCGA-LUAD cohort was randomly divided into training (n = 229) and testing (n = 98) sets. We extracted quantitative image features from histopathological slides of patients with LUAD using computational approaches, constructed a predictive model for AURKA expression in the training set, and estimated their predictive performance in the test set. A Cox proportional hazards model was used to assess whether the pathomic scores (PS) generated by the model independently predicted LUAD survival. ResultsHigh AURKA expression was an independent risk factor for overall survival (OS) in patients with LUAD (hazard ratio = 1.816, 95 % confidence intervals = 1.257–2.623, P = 0.001). The model based on histopathological image features had significant predictive value for AURKA expression: the area under the curve of the receiver operating characteristic curve in the training set and validation set was 0.809 and 0.739, respectively. Decision curve analysis showed that the model had clinical utility. Patients with high PS and low PS had different survival rates (P = 0.019). Multivariate analysis suggested that PS was an independent prognostic factor for LUAD (hazard ratio = 1.615, 95 % confidence intervals = 1.071–2.438, P = 0.022). ConclusionPathomics models based on machine learning can accurately predict AURKA expression and the PS generated by the model can predict LUAD prognosis.