Conditional survival analysis and real-time prognosis prediction in stage III T3-T4 colon cancer patients after surgical resection: a SEER database analysis.

BACKGROUND: Conditional survival (CS) takes into consideration the duration of survival post-surgery and can provide valuable additional insights. The aim of this study was to investigate the risk factors associated with reduced one-year postoperative conditional survival in patients diagnosed with stage III T3-T4 colon cancer and real-time prognosis prediction. Furthermore, we aim to develop pertinent nomograms and predictive models. METHODS: Clinical data and survival outcomes of patients diagnosed with stage III T3-T4 colon cancer were obtained from the Surveillance, Epidemiology, and End Results (SEER) database, covering the period from 2010 to 2019. Patients were divided into training and validation cohorts at a ratio of 7:3. The training set consisted of a total of 11,386 patients for conditional overall survival (cOS) and 11,800 patients for conditional cancer-specific survival (cCSS), while the validation set comprised 4876 patients for cOS and 5055 patients for cCSS. Univariate and multivariate Cox regression analyses were employed to identify independent risk factors influencing one-year postoperative cOS and cCSS. Subsequently, predictive nomograms for cOS and cCSS at 2-year, 3-year, 4-year, and 5-year intervals were constructed based on the identified prognostic factors. The performance of these nomograms was rigorously assessed through metrics including the concordance index (C-index), calibration curves, and the area under curve (AUC) derived from the receiver operating characteristic (ROC) analysis. Clinical utility was further evaluated using decision curve analysis (DCA). RESULTS: A total of 18,190 patients diagnosed with stage III T3-T4 colon cancer were included in this study. Independent risk factors for one-year postoperative cOS and cCSS included age, pT stage, pN stage, pretreatment carcinoembryonic antigen (CEA) levels, receipt of chemotherapy, perineural invasion (PNI), presence of tumor deposits, the number of harvested lymph nodes, and marital status. Sex and tumor site were significantly associated with one-year postoperative cOS, while radiation therapy was notably associated with one-year postoperative cCSS. In the training cohort, the developed nomogram demonstrated a C-index of 0.701 (95% CI, 0.711-0.691) for predicting one-year postoperative cOS and 0.701 (95% CI, 0.713-0.689) for one-year postoperative cCSS. Following validation, the C-index remained robust at 0.707 (95% CI, 0.721-0.693) for one-year postoperative cOS and 0.700 (95% CI, 0.716-0.684) for one-year postoperative cCSS. ROC and calibration curves provided evidence of the model's stability and reliability. Furthermore, DCA underscored the nomogram's superior clinical utility. CONCLUSIONS: Our study developed nomograms and predictive models for postoperative stage III survival in T3-T4 colon cancer with the aim of accurately estimating conditional survival. Survival bias in our analyses may lead to overestimation of survival outcomes, which may limit the applicability of our findings.

Comparing the short-term clinical outcomes and therapeutic effects of different colectomies in patients with refractory slow-transit constipation in eastern countries: a network meta-analysis.

Surgical treatment has been widely used in patients with refractory slow transit constipation (RSTC). The aim of this network meta-analysis (NMA) was to compare the effects of different colectomies on short-term postoperative complications and quality of life in patients with RSTC. Electronic literature searches were performed in the PubMed, Web of Science, EMBASE, WANFANG DATA, and Cochrane Central Register of controlled trials databases and were searched up to December 2022. Selected to compare the short-term clinical outcomes and quality of life of the treatment of RSTC. A random-effects Bayesian NMA was conducted to assess and rank the effectiveness of different surgical modalities. This study included a total of six non-randomized controlled trials involving 336 subjects. It was found that subtotal colectomy with cecorectal anastomosis (CRA) demonstrated superior effectiveness in several aspects, including reduced hospital stay (MD 0.06; 95% CI [0.02, 1.96]), shorter operative time (MD 4.75; 95% CI [0.28, 14.07]), lower constipation index (MD 0.61; 95% CI [0.04, 1.71]), improved quality of life (MD 4.42; 95% CI [0.48, 4.42]). Additionally, in terms of short-term clinical outcomes, subtotal colectomy with ileosigmoidal anastomosis (SC-ISA) procedure ranked the highest in reducing small bowel obstruction (OR 0.24; 95% CI [0.02, 0.49]), alleviating abdominal pain (OR 0.53; 95% CI [0.05, 1.14]), minimizing abdominal distension (OR 0.33; 95% CI [0.02, 0.65]), and reducing incision infection rates (OR 0.17; 95% CI [0.01, 0.33]). Furthermore, SC-ISA ranked as the best approach in terms of patient satisfaction (OR 0.66; 95% CI [0.02, 1.46]). Based on our research findings, we recommend that CRA be considered as the preferred treatment approach for patients diagnosed with RSTC.

Mitochondrial DNA Haplogroups and SNPs: Risk Factors in Multiple Cancers Based on a Cross-Tumor Analysis in Chinese Population.

BACKGROUND: Mitochondrial DNA's (mtDNA) haplogroups and SNPs were associated with the risk of different cancer. However, there is no evidence that the same haplogroup or mitochondrial SNP (mtSNP) exhibits the pleiotropic effect on multiple cancers. METHODS: We recruited 2,489 participants, including patients with colorectal, hepatocellular, lung, ovarian, bladder, breast, pancreatic, and renal cell carcinoma. In addition, 715 healthy individuals from Northern China served as controls. Next, cross-tumor analysis was performed to determine whether mtDNA variation is associated with multiple cancers. RESULTS: Our results revealed a significant decrease in the occurrence risk of multiple cancers among individuals belonging to haplogroup A [OR = 0.553, 95% confidence interval (CI) = 0.375-0.815, P = 0.003]. Furthermore, we identified 11 mtSNPs associated with multiple cancers and divided the population into high-risk and low-risk groups. Low-risk groups showed a significantly reduced risk of occurrence compared with high-risk groups (OR = 0.614, 95% CI = 0.507-0.744, P < 0.001). Furthermore, using interaction analysis, we identified a special group of individuals belonging to haplogroup A/M7 and the low-risk population, who exhibit a lower risk of multiple cancers compared with other populations (OR = 0.195, 95% CI = 0.106-0.359, P < 0.001). Finally, gene set enrichment analysis confirmed that haplogroup A/M7 patients had lower expression levels of cancer-related pathway genes compared with haplogroup D patients. CONCLUSIONS: We found that specific mtDNA haplogroups and mtSNPs may play a role in predicting multiple cancer predisposition in Chinese populations. IMPACT: This may provide a potential tool for early screening in clinical settings for individuals in the Chinese population.

Association of hemicolectomy with survival in stage II colorectal cancer: a retrospective cohort study.

To compare the oncological survival outcomes of partial colectomy (PC) and hemicolectomy (HC) in patients with stage II colon cancer. A total of 18,795 patients with stage II colon cancer who underwent hemicolectomy (n = 12,022) or partial colectomy (n = 6773) from 2010 to 2019 were included in the the Surveillance, Epidemiology, and End Results (SEER) database. Overall survival (OS) and cancer-specific survival (CSS) were compared between the two groups, and the threshold of harvested lymph nodes was determined. The results showed that age, gender, race, tumor site, scope of regional lymph nodes, postoperative chemotherapy, postoperative radiotherapy, harvested lymph nodes, and tumor size were significantly different between the PC and HC groups (all P < 0.05). The OS rate was slightly lower in hemicolectomy patients than in partial colectomy patients (69.9% vs. 74.5%, respectively, P < 0.001), but CSS was similar between the two groups (87.9% vs. 88.1%, respectively, P = 0.32). After propensity score matching (PSM) was performed, the OS and CSS rates in the two groups were significantly different (CSS 84.3% vs. 88.0%, P < 0.001; OS 62.2% vs. 72.5%, P < 0.001). The survminer R package determined that the optimum threshold for the harvested lymph node count in stage II colon cancer patients was 16. CSS was significantly different between patients with ≥ 12 lymph nodes harvested and patients with ≥ 16 lymph nodes harvested (P = 0.043). Univariate and multivariate Cox regression and survival analyses of stage II colon cancer patients showed that the survival benefit of stage II colon cancer patients receiving partial colectomy was superior to that of patients receiving hemicolectomy. Partial colectomy has significant oncological benefits over hemicolectomy in the treatment of stage II colon cancer patients, even in the case of pT4b or tumor deposits. Removal of 16 lymph nodes during colectomy for stage II colon cancer correlated with improved survival, and this threshold was more effective than the standard threshold of 12 lymph nodes in distinguishing between patients with good and poor prognoses.

Camrelizumab combined with apatinib in the treatment of patients with hepatocellular carcinoma: a real-world assessment.

Although a phase II clinical trial confirmed that camrelizumab combined with apatinib is effective in patients with hepatocellular carcinoma (HCC), we generally lack data on the results of this regimen in real-world clinical practice. In this study, the efficacy and safety of camrelizumab combined with apatinib in the treatment of patients with HCC were re-evaluated. Data from 86 patients with HCC were collected and combinatorically treated with camrelizumab and apatinib at the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China. The objective remission rate and disease control rate were 25.6% and 72.1%, respectively. The median progression-free survival was 5 months (95% CI 3.7-6.3 months), and the median overall survival time was 19.0 months (95% CI 16.9-21.1 months). The 12- and 18-month survival rates were 70.9% and 54.2%, respectively. The most common grade 3-4 adverse events were hypertension (24.4%), thrombocytopenia (16.3%), and hyperbilirubinemia (9.3%). Multivariate regression analysis showed that operation history was an independent risk factor for overall survival.

Effect of adjuvant radiotherapy after breast-conserving surgery in elder women with early-stage breast cancer: a propensity-score matching analysis.

Purpose: The study aimed to explore the role of adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) in elder women with early-stage breast cancer (BC). Methods: BC patients with 70-79 years of age, stage T1-2N0-1M0, undergoing BCS were screened in the Surveillance, Epidemiology and End Results (SEER) database between 2010 and 2015. The clinicopathological characteristics were balanced with propensity-score matching (PSM) method. Kaplan-Meier curves and Cox regression analyses were performed to determine the impact of adjuvant RT on BC patients. Results: Ultimately, 12,310 patients treated with adjuvant RT and 4837 patients treated with no RT, were involved in the analysis. Overall, patients treated with adjuvant RT was associated with a better breast cancer-specific survival (BCSS) (HR: 1.980 [1.596- 2.456], P < 0.001) and overall survival (OS) (HR: 2.214 [1.966- 2.494], P < 0.001) than those who did not undergo RT. After 1:1 PSM, adjuvant RT still performed advantage in both BCSS (HR: 1.918 [1.439- 2.557], P < 0.001) and OS (HR: 2.235 [1.904- 2.624], P < 0.001). In the multivariate COX analysis of BCSS, widowed, divorced and separated patients, tumor grade III, T2 stage, N1 stage, no RT, molecular subtypes with luminal B and triple negative were associated with a shorter BCSS (P < 0.05). In the multivariate COX analysis of OS, age ≥74 years, widowed, divorced and separated patients, tumor grade II/III, T2 stage, no RT, no chemotherapy, molecular subtypes with triple negative were associated with a shorter OS (P < 0.05). Furthermore, the advantages of adjuvant RT were observed in all subgroup analysis. Conclusion: Adjuvant RT after BCS can improve both BCSS and OS in elderly patients with early-stage BC. Additionally, all subgroups analysis-derived BCSS and OS were in support of RT.

Assessing the effectiveness of camrelizumab plus apatinib versus sorafenib for the treatment of primary liver cancer: a single-center retrospective study.

Although the effectiveness of camrelizumab plus apatinib has been confirmed in a phase II clinical study, the efficacy of camrelizumab plus apatinib versus sorafenib for primary liver cancer (PLC) remains unverified. We retrospectively collected the data of 143 patients with PLC who received camrelizumab plus apatinib or sorafenib as the first-line treatment at The First Affiliated Hospital of Anhui Medical University from April 2018 to November 2021. Of these, 71 patients received an intravenous injection of camrelizumab 200 mg (body weight ≥ 50 kg) or 3 mg/kg (body weight < 50 kg) followed by an oral dosage of apatinib 250 mg/day every 3 weeks and 72 patients received sorafenib 400 mg orally, twice a day in 28-day cycles. The primary outcomes were overall survival and progression-free survival. The secondary outcomes were objective response rate, disease control rate, and safety. The median median progression-free survival and median overall survival with camrelizumab plus apatinib and sorafenib were 6.0 (95% confidence interval (CI) 4.2-7.8) and 3.0 months (95% CI 2.3-3.7) and 19.0 (95% CI 16.4-21.6) and 12.0 months (95% CI 8.9-15.1), respectively (death hazard ratio: 0.61, P = 0.023). Grade 3/4 treatment-related adverse events were noted in 50 (70.4%) patients in the camrelizumab plus apatinib group and 19 (26.4%) patients in the sorafenib group. Two treatment-related deaths were recorded. Clinically significant improvements were observed in overall survival and progression-free survival with camrelizumab plus apatinib versus sorafenib. Although the side effects of camrelizumab plus apatinib are relatively high, they can be controlled.

Prognosis and therapeutic benefits prediction based on NK cell marker genes through single-cell RNA-seq with integrated bulk RNA-seq analysis for hepatocellular carcinoma.

Tumor-infiltrating immune cells greatly participate in regulating tumorigenesis and metastasis of hepatocellular carcinoma (HCC). Natural killer cell, as an important role of innate immunity, plays an indispensable role in antitumor immunity and regulate tumor development. In this study, we firstly identified 251 NK cell marker genes of HCC based on single-cell RNA sequencing data. Subsequently, an NK cell marker genes-related prognostic signature (NKPS) was developed in the cancer genome atlas (TCGA) cohort for risk stratification and prognosis prediction. The predictive value of the NKPS in prognosis was well validated in different clinical subgroups and three external datasets (ICGC-LIHC cohort, GSE14520 cohort and Guilin cohort). Moreover, multivariate analysis revealed the independent prognostic value of NKPS for OS in HCC. Further functional analysis indicated the NKPS was associated with basic cellular processes, that may contribute to the development and progression of HCC. Thereafter, immune characteristics as well as the therapeutic benefits in NKPS risk score-defined subgroups were analyzed. Patients with low-risk score exhibited immune-active status, manifested as higher immune scores, more infiltration of CD8+ T cells and macrophage M1, and higher T-cell receptor (TCR) richness and diversity. Remarkably, the NKPS was negatively correlated with immunotherapy response-related signatures. In addition, the low-risk group exhibited significantly improved therapeutic benefits, either from immunotherapy or traditional chemotherapy and target therapy. Overall, the NKPS showed an excellent predictive value for prognosis and therapeutic responses for HCC, which might also provide novel insights into better HCC management strategies.

Radiomics model based on contrast-enhanced computed tomography to predict early recurrence in patients with hepatocellular carcinoma after radical resection.

BACKGROUND: Radical resection remains an effective strategy for patients with hepatocellular carcinoma (HCC). Unfortunately, the postoperative early recurrence (recurrence within 2 years) rate is still high. AIM: To develop a radiomics model based on preoperative contrast-enhanced computed tomography (CECT) to evaluate early recurrence in HCC patients with a single tumour. METHODS: We enrolled a total of 402 HCC patients from two centres who were diagnosed with a single tumour and underwent radical resection. First, the features from the portal venous and arterial phases of CECT were extracted based on the region of interest, and the early recurrence-related radiomics features were selected via the least absolute shrinkage and selection operator proportional hazards model (LASSO Cox) to determine radiomics scores for each patient. Then, the clinicopathologic data were combined to develop a model to predict early recurrence by Cox regression. Finally, we evaluated the prediction performance of this model by multiple methods. RESULTS: A total of 1915 radiomics features were extracted from CECT images, and 31 of them were used to determine the radiomics scores, which showed a significant difference between the early recurrence and nonearly recurrence groups. Univariate and multivariate Cox regression analyses showed that radiomics scores and serum alpha-fetoprotein were independent indicators, and they were used to develop a combined model to predict early recurrence. The area under the receiver operating characteristic curve values for the training and validation cohorts were 0.77 and 0.74, respectively, while the C-indices were 0.712 and 0.674, respectively. The calibration curves and decision curve analysis showed satisfactory accuracy and clinical utilities. Kaplan-Meier curves based on recurrence-free survival and overall survival showed significant differences. CONCLUSION: The preoperative radiomics model was shown to be effective for predicting early recurrence among HCC patients with a single tumour.

Dominant neoantigen verification in hepatocellular carcinoma by a single-plasmid system coexpressing patient HLA and antigen.

BACKGROUND: Previous studies confirmed that most neoantigens predicted by algorithms do not work in clinical practice, and experimental validations remain indispensable for confirming immunogenic neoantigens. In this study, we identified the potential neoantigens with tetramer staining, and established the Co-HA system, a single-plasmid system coexpressing patient human leukocyte antigen (HLA) and antigen, to detect the immunogenicity of neoantigens and verify new dominant hepatocellular carcinoma (HCC) neoantigens. METHODS: First, we enrolled 14 patients with HCC for next-generation sequencing for variation calling and predicting potential neoantigens. Then, the Co-HA system was established. To test the feasibility of the system, we constructed target cells coexpressing HLA-A*11:01 and the reported KRAS G12D neoantigen as well as specific T-cell receptor (TCR)-T cells. The specific cytotoxicity generated by this neoantigen was shown using the Co-HA system. Moreover, potential HCC-dominant neoantigens were screened out by tetramer staining and validated by the Co-HA system using methods including flow cytometry, enzyme-linked immunospot assay and ELISA. Finally, antitumor test in mouse mode and TCR sequencing were performed to further evaluate the dominant neoantigen. RESULTS: First, 2875 somatic mutations in 14 patients with HCC were identified. The main base substitutions were C>T/G>A transitions, and the main mutational signatures were 4, 1 and 16. The high-frequency mutated genes included HMCN1, TTN and TP53. Then, 541 potential neoantigens were predicted. Importantly, 19 of the 23 potential neoantigens in tumor tissues also existed in portal vein tumor thrombi. Moreover, 37 predicted neoantigens restricted by HLA-A*11:01, HLA-A*24:02 or HLA-A*02:01 were performed by tetramer staining to screen out potential HCC-dominant neoantigens. HLA-A*24:02-restricted epitope 5'-FYAFSCYYDL-3' and HLA-A*02:01-restricted epitope 5'-WVWCMSPTI-3' demonstrated strong immunogenicity in HCC, as verified by the Co-HA system. Finally, the antitumor efficacy of 5'-FYAFSCYYDL-3'-specific T cells was verified in the B-NDG-B2mtm1Fcrntm1(mB2m) mouse and their specific TCRs were successfully identified. CONCLUSION: We found the dominant neoantigens with high immunogenicity in HCC, which were verified with the Co-HA system.

The predictive value of PD-L1 expression in patients with advanced hepatocellular carcinoma treated with PD-1/PD-L1 inhibitors: A systematic review and meta-analysis.

BACKGROUND AND AIM: Programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors have transformed the treatment landscape of advanced hepatocellular carcinoma (HCC), but consistent responses are not observed in all patients, and prognostic biomarkers to guide treatment decisions are lacking. We aimed to evaluate the predictive value of PD-L1 expression in advanced HCC patients treated with PD-1/PD-L1 inhibitors. METHODS: A comprehensive search of PubMed, Embase, Web of Science, and the Cochrane Library was conducted. Studies comparing the objective response rate (ORR) and/or disease control rate (DCR) based on the tumor PD-L1 status of HCC were included. RESULTS: Eleven studies with 1,330 HCC patients treated with PD-1/PD-L1 inhibitors were included. Pooled odds ratio (OR) analysis demonstrated a significantly improved ORR in PD-L1-positive patients compared with PD-L1-negative patients (OR, 1.86, 95% CI, 1.35-2.55). Similar results were observed in the anti-PD-1 treatment (p < 0.001) and anti-PD-1/PD-L1 monotherapy (p < 0.001) subgroups. The pooled ORRs in the PD-L1-positive and PD-L1-negative groups were 26% (95% CI, 20%-32%) and 18% (95% CI, 13%-22%), respectively. For DCR, the pooled OR analysis showed no significant difference between PD-L1-positive patients and PD-L1-negative patients (66% [95% CI, 55%-76%] vs. 69% [95% CI, 62%-76%]; OR, 0.92, 95% CI, 0.59-1.44). The results were consistent across the drug target and combination treatment subgroups. CONCLUSION: Positive PD-L1 expression is associated with a better ORR in advanced HCC patients treated with anti-PD-1/PD-L1-based therapies. This feature can help to identify HCC patients who will benefit most from PD-1/PD-L1 inhibitors.

A signature based on NKG2D ligands to predict the recurrence of hepatocellular carcinoma after radical resection.

INTRODUCTION: Due to the high recurrence, the HCC prognosis remains poor. Yet, the biomarkers for predicting the recurrence of high-risk patients are currently lacking. We aimed to develop a signature to predict the recurrence of HCC based on NKG2D ligands. METHODS: The multivariate Cox proportional hazards regression was used to select recurrence-related variables of NKG2D ligands in HCC patients from The Cancer Genome Atlas (TCGA). HCC patients from the OEP000321 dataset and Guilin cohort were used to validate the predictive signature. The mRNA expression of NKG2D ligands was measured by QRT-PCR. Immunohistochemistry analysis of HCC tissue microarray samples was used to identify the expression of NKG2D ligands. RESULTS: In this study, NKG2D ligands expression in the mRNA and protein level was both abnormally expressed in HCC and associated with recurrence-free survival (RFS). Then, the recurrence-related variables of NKG2D ligands in HCC were selected by the multivariate Cox proportional hazards regression. Among the eight NKG2D ligands, MICA (HR = 1.347; 95% CI = 1.012-1.793; p = 0.041), ULBP3 (HR = 0.453; 95% CI = 0.231-0.889; p = 0.021) and ULBP5 (HR = 3.617; 95% CI = 1.819-7.194; p < 0.001) were significantly correlated with RFS in the TCGA-LIHC cohort. Then, the signature was constructed by the three NKG2D ligands. The predictive effectiveness of this signature was also validated in the OEP000321 dataset and Guilin cohort. Further, HCC patients were classified into low-risk and high-risk subgroups by the predictive score. Compared with the low-risk group, the high-risk group had poor RFS in both training and validation cohorts. Importantly, compared with the low-risk patients with the G1-G2 stage, the levels of infiltrated NK-activated cells and NKG2D expression were both lower in the high-risk patients. CONCLUSIONS: The signature based on MICA, ULBP3, and ULBP5 could predict HCC recurrence.

Patterns of care and prognostic evaluation for stage I-III upper esophageal squamous cell carcinoma: a population-based study.

Background: There is no strong evidence regarding the optimal treatment and specific prognosis prediction model for upper esophageal squamous cell carcinoma (UESCC). This study aimed to investigate the real-world treatment patterns and develop models to predict overall survival (OS) and esophageal cancer-specific survival (ECSS) in patients with stage I-III UESCC. Methods: Patients with T1-4N0-3M0 UESCC in the Surveillance, Epidemiology, and End Results (SEER) database were identified from 2010 to 2017, and randomized to a training cohort and a validation cohort. The effect of treatment patterns on survival were comprehensively analyzed. Nomograms were developed by incorporating independent prognostic factors analyzed by Cox regression in the training cohort and evaluated by the concordance index (C-index), receiver operating characteristic (ROC) curves, calibration curves, and decision curve analyses (DCA) in two cohorts. Results: A total of 677 patients were identified, including 452 in the training cohort and 225 in the validation cohort. Among all populations, 71.9% (487) received chemoradiotherapy without surgery, and chemoradiotherapy or/and surgery showed better survival than other treatments. However, surgery was rarely carried out for patients with stage II-III. T stage, N stage, surgery, chemotherapy, and radiotherapy were independent risks for both OS and ECSS, while age was also an independent risk for OS. The C-indexes for nomograms to predict OS (0.71 and 0.72) and ECSS (0.70 and 0.73) were greater than 7th AJCC staging system to predict OS (0.61 and 0.64) and ECSS (0.64 and 0.64) in both the training cohort and the validation cohort. Time-dependent ROC curves and DCA also suggested that nomograms performed consistently better than 7th AJCC staging system. The calibration curves demonstrated good consistency in predicting survival. Conclusions: Chemoradiotherapy was a major treatment with preferable survival for patients with stage I-III UESCC. We have firstly developed and validated prognostic nomograms in patients with stage I-III UESCC, which would play a supplementary role in the current staging system.

IGFBP1hiWNT3Alo Subtype in Esophageal Cancer Predicts Response and Prolonged Survival with PD-(L)1 Inhibitor.

PD-(L)1 inhibitor could improve the survival of locally advanced esophageal cancer (ESCA) patients, but we cannot tailor the treatment to common biomarkers. WNT signaling activation was associated with primary resistance to immunotherapy. In this study, we used our two clinical cohorts (BJCH n = 95, BJIM n = 21) and three public cohorts to evaluate and verify a new immunotherapeutic biomarker based on WNT signaling in ESCA patients. Our findings showed that WNT signaling-related genes stratified TCGA patients into Cluster 1, 2, and 3, among which, Cluster 3 had the worst prognosis. The most up- and down-regulated genes in Cluster 3 were IGFBP1 and WNT3A. Further analysis validated that IGFBP1hiWNT3Alo ESCA patients had significantly poor RFS and OS in the TCGA and BJCH cohorts. Interestingly, IGFBP1hiWNT3Alo patients had a good response and prognosis with immunotherapy in three independent cohorts, exhibiting better predictive value than PD-L1 expression (signature AUC = 0.750; PD-L1 AUC = 0.571). Moreover, IGFBP1hiWNT3Alo patients may benefit more from immunotherapy than standard treatment (p = 0.026). Immune cell infiltration analysis revealed a significant increase in DC infiltration in IGFBP1hiWNT3Alo patients post-immunotherapy (p = 0.022), which may enhance immune response. The IGFBP1hiWNT3Alo signature could predict patients who benefited from PD-(L)1 inhibitor treatment and may serve as a biomarker in ESCA.

Novel index for the prediction of significant liver fibrosis and cirrhosis in chronic hepatitis B patients in China.

BACKGROUND: Noninvasive, practical, and convenient means of detection for the prediction of liver fibrosis and cirrhosis in China are greatly needed. AIM: To develop a precise noninvasive test to stage liver fibrosis and cirrhosis. METHODS: With liver biopsy as the gold standard, we established a new index, [alkaline phosphatase (U/L) + gamma-glutamyl transpeptidase (U/L)/platelet (109/L) (AGPR)], to predict liver fibrosis and cirrhosis. In addition, we compared the area under the receiver operating characteristic curve (AUROC) of AGPR, gamma-glutamyl transpeptidase to platelet ratio, aspartate transaminase to platelet ratio index, and FIB-4 and evaluated the accuracy of these routine laboratory indices in predicting liver fibrosis and cirrhosis. RESULTS: Correlation analysis revealed a significant positive correlation between AGPR and liver fibrosis stage (P < 0.001). In the training cohort, the AUROC of AGPR was 0.83 (95%CI: 0.78-0.87) for predicting fibrosis (≥ F2), 0.84 (95%CI: 0.79-0.88) for predicting extensive fibrosis (≥ F3), and 0.87 (95%CI: 0.83-0.91) for predicting cirrhosis (F4). In the validation cohort, the AUROCs of AGPR to predict ≥ F2, ≥ F3 and F4 were 0.83 (95%CI: 0.77-0.88), 0.83 (95%CI: 0.77-0.89), and 0.84 (95%CI: 0.78-0.89), respectively. CONCLUSION: The AGPR index should become a new, simple, accurate, and noninvasive marker to predict liver fibrosis and cirrhosis in chronic hepatitis B patients.

Functional Roles of Chemokine Receptor CCR2 and Its Ligands in Liver Disease.

Chemokines are a family of cytokines that orchestrate the migration and positioning of immune cells within tissues and are critical for the function of the immune system. CCR2 participates in liver pathology, including acute liver injury, chronic hepatitis, fibrosis/cirrhosis, and tumor progression, by mediating the recruitment of immune cells to inflammation and tumor sites. Although a variety of chemokines have been well studied in various diseases, there is no comprehensive review presenting the roles of all known chemokine ligands of CCR2 (CCL2, CCL7, CCL8, CCL12, CCL13, CCL16, and PSMP) in liver disease, and this review aims to fill this gap. The introduction of each chemokine includes its discovery, its corresponding chemotactic receptors, physiological functions and roles in inflammation and tumors, and its impact on different immune cell subgroups.

Preoperative Radiomics Analysis of Contrast-Enhanced CT for Microvascular Invasion and Prognosis Stratification in Hepatocellular Carcinoma.

Purpose: Microvascular invasion (MVI) impairs long-term prognosis of patients with hepatocellular carcinoma (HCC). We aimed to develop a novel nomogram to predict MVI and patients' prognosis based on radiomic features of contrast-enhanced CT (CECT). Patients and Methods: HCC patients who underwent curative resection were enrolled. The radiomic features were extracted from the region of tumor, and the optimal MVI-related radiomic features were selected and applied to construct radiomic signature (Rad-score). The prediction models were created according to the logistic regression and evaluated. Biomarkers were analyzed via q-PCR from randomly selected HCC patients. Correlations between biomarkers and radiomic signature were analyzed. Results: A total of 421 HCC patients were enrolled. A total of 1962 radiomic features were extracted from the region of tumor, and the 11 optimal MVI-related radiomic features showed a favor predictive ability with area under the curves (AUCs) of 0.796 and 0.810 in training and validation cohorts, respectively. Aspartate aminotransferase (AST), tumor number, alpha-fetoprotein (AFP) level, and radiomics signature were independent risk factors of MVI. The four factors were integrated into the novel nomogram, named as CRM, with AUCs of 0.767 in training cohort and 0.793 in validation cohort for predicting MVI, best among radiomics signature alone and clinical model. The nomogram was well-calibrated with favorable clinical value demonstrated by decision curve analysis and can divide patients into high- or low-risk subgroups of recurrence and mortality. In addition, gene BCAT1, DTGCU2, DOCK3 were analyzed via q-PCR and serum AFP were identified as having significant association with radiomics signature. Conclusion: The novel nomogram demonstrated good performance in preoperatively predicting the probability of MVI, which might guide clinical decision.

Predictive potential of Nomogram based on GMWG for patients with hepatocellular carcinoma after radical resection.

BACKGROUND: Since it's a challenging task to precisely predict the prognosis of patients with hepatocellular carcinoma (HCC). We developed a nomogram based on a novel indicator GMWG [(Geometric Mean of gamma-glutamyltranspeptidase (GGT) and white blood cell (WBC)] and explored its potential in the prognosis for HCC patients. METHODS: The patients enrolled in this study were randomly assigned to training and validation cohorts. And we performed the Least Absolute Shrinkage and Selection Operator proportional hazards model (LASSO Cox) model with clinical characteristics, serum indexes, and novel GMWG. Multivariate analysis was performed to build a nomogram. The performance of the nomogram was evaluated by C-index, the area under the receiver operating characteristic curve (AUC), and the calibration curve. Kaplan-Meier curves showed discrimination of the nomogram. Clinical utility was assessed by decision curve analysis (DCA). The discrimination ability of the nomogram was determined by the net reclassification index (NRI). RESULTS: The geometric mean of GGT and white WBC count (GMWG), neutrophil to lymphocyte ratio (NLR), and tumor size were significantly associated with the overall survival (OS). The variables above were used to develop the nomogram. The indexes of nomogram were 0.70 and 071 in the training or validation cohort, respectively. AUC of 1-, 3- and 5-year OS showed satisfactory accuracy as well. The calibration curve showed agreement between the ideal and predicted values. Kaplan-Meier curves based on the overall survival (OS) and disease-free survival (DFS) showed significant differences between nomogram predictive low and high groups. DCA showed clinical utilities while NRI showed discrimination ability in both training or validation cohort. CONCLUSIONS: GMWG might be a potential prognostic indicator for patients with HCC. The nomogram containing GMWG also showed satisfaction prediction capacity.

The effects of radiotherapy after thoracic and laparoscopic surgery on patients with esophageal cancer and on their prognoses.

OBJECTIVE: This paper aimed to explore the effects of radiotherapy after thoracic and laparoscopic surgery (TLS) in patients with esophageal cancer and on their prognoses. METHODS: Altogether 118 patients with esophageal cancer diagnosed in our hospital were recruited as the study cohort and randomly divided into a postoperative radiotherapy group (59 cases) and a postoperative chemotherapy group (59 cases). All the patients were treated with TLS. In addition to the TLS, the patients in the postoperative radiotherapy group underwent radiotherapy, and the patients in the postoperative chemotherapy group were administered cisplatin and 5-fluorouracil (PF) chemotherapy. Before the treatment and at 6 months after the treatment, the serum carbohydrate antigen 199 (CA199), carbohydrate antigen 153 (CA153), and carcinoembryonic antigen (CEA) levels were measured using immunity transmission turbidity (ITT). The expression levels of Bax and Bcl-2 in the peripheral blood mononuclear cells (PBMCs) were measured using Western blot (WB). The CD4+, CD8+ and CD3+ levels in the peripheral venous blood were measured using a flow cytometer. The two groups were compared in terms of their effective treatment rates, their incidences of complications, and their postoperative survival rates. RESULTS: After the treatment, the serum CEA, CA153, and CA199 levels in the postoperative radiotherapy group were significantly lower than they were in the postoperative chemotherapy group (P<0.05). After the treatment, the expression level of Bcl-2 was significantly lower in the postoperative radiotherapy group, but the Bax expression level was significantly higher in the postoperative radiotherapy group (P<0.05). After the treatment, there were no statistically significant differences in the CD4+, CD3+ or CD8+ levels between the two groups (P>0.05). After the treatment, the overall response rate (ORR) and the total incidence of adverse reactions were significantly higher in the postoperative radiotherapy group (P<0.05). After the treatment, the 1-year, 3-year, and 5-year survival rates were significantly elevated in the postoperative radiotherapy group (P<0.05). CONCLUSION: Compared with the esophageal cancer patients treated with chemotherapy after TLS, the serum CA153, CA199, and CEA levels were significantly improved in the patients treated with radiotherapy. The Bcl-2 and Bax levels in the PBMCs tended close to normal. Therefore, undergoing radiotherapy after TLS is markedly effective in prolonging patients' survival times and improving their prognoses.

Neoantigen vaccine: An emerging immunotherapy for hepatocellular carcinoma.

Tumor-specific neoantigens, which are expressed on tumor cells, can induce an effective antitumor cytotoxic T-cell response and mediate tumor regression. Among tumor immunotherapies, neoantigen vaccines are in early human clinical trials and have demonstrated substantial efficiency. Compared with more neoantigens in melanoma, the paucity and inefficient identification of effective neoantigens in hepatocellular carcinoma (HCC) remain enormous challenges in effectively treating this malignancy. In this review, we highlight the current development of HCC neoantigens in its generation, screening, and identification. We also discuss the possibility that there are more effective neoantigens in hepatitis B virus (HBV)-related HCC than in non-HBV-related HCC. In addition, since HCC is an immunosuppressive tumor, strategies that reverse immunosuppression and enhance the immune response should be considered for the practical exploitation of HCC neoantigens. In summary, this review offers some strategies to solve existing problems in HCC neoantigen research and provide further insights for immunotherapy.