Tumor Lymph Node Metastasis Research Articles

CD69+CD103+CD8+ tissue-resident memory T cells possess stronger anti-tumor activity and predict better prognosis in colorectal cancer

BackgroundColorectal cancer (CRC) is one of the most prevalent cancers worldwide. Despite advancements in therapeutic methodologies, it still causes a high rate of patient mortality. CD8+ tissue-resident memory T (TRM) cells are strategically positioned to mediate effective anti-tumor responses. However, the characteristic surface molecules and functions of CD8+ TRM cells exhibit significant heterogeneity.MethodsThe roles and anti-tumor biological functions of different CD8+ TRM subsets in CRC were determined by clinical CRC samples, bioinformatics analysis, and in vitro experiments including co-culture experiments and transwell migration assays. The signaling pathways that synergistically regulate the differentiation of CD8+ TRM cells were identified by in vitro CD8+ T cell activation and inhibition assays, and the functioning transcription factors were predicted using the UCSC and JASPAR databases.ResultsWe found that different CD8+ TRM subsets existed in CRC tumor tissues, which were identified as CD69−CD103−CD8+ TRM, CD69+CD103−CD8+ TRM (SP CD8+ TRM), and CD69+CD103+CD8+ TRM (DP CD8+ TRM) subsets. Compared with SP CD8+ TRM cells, increased infiltration of DP CD8+ TRM cells predicted better prognosis and played a protective role mainly in tumor invasion and lymph node metastasis of CRC. DP CD8+ TRM cells expressed higher levels of effector molecules and exerted stronger anti-tumor effects in a FAS/FASL pathway-dependent manner. Additionally, DP CD8+ TRM cells secreted higher levels of CXCL13 and recruited B cells into tumor tissues through the CXCL13/CXCR5 signaling axis to form tertiary lymphoid structures, participating in anti-tumor immune responses. Notch and TGF-β signaling pathways synergistically regulate the differentiation of DP CD8+ TRM cells.ConclusionsWe clarified the roles and mechanisms of different CD8+ TRM subsets in CRC and identified that DP CD8+ TRM cells exert stronger anti-tumor effects and predict better prognosis, which provides ideas for developing new clinically available therapeutic targets.

EIF4A3-Induced hsa_circ_0118578 Expression Enhances the Tumorigenesis of Papillary Thyroid Cancer.

Background: Circular RNA (circRNA) plays a regulatory role in the malignancy of papillary thyroid cancer (PTC). However, the role of a novel circRNA, hsa_circ_0118578, in PTC is not yet fully understood. This report focuses on unveiling hsa_circ_0118578's effect on PTC cell malignancy and reveals its mechanism in PTC progression. Methods: Levels of hsa_circ_0118578 in PTC were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). The functional roles of hsa_circ_0118578 in PTC cell malignancy were evaluated through Transwell, 5-ethynyl-2'-deoxyuridine (EdU), and wound healing assays. A xenograft model in nude mice was used to examine the effects of hsa_circ_0118578's invivo. The interaction between eukaryotic translation initiation factor 4A3 (EIF4A3) and hsa_circ_0118578 was confirmed using RNA-binding protein immunoprecipitation, qRT-PCR, and western blotting. Results: The hsa_circ_0118578 with high expression in PTC tissues was associated with higher tumor node metastasis stage, lymph node metastasis, as well as poor differentiation. Cell functional assays demonstrated that silencing hsa_circ_0118578 inhibited PTC cell proliferation, invasion, and migration. In the xenograft assay, tumorigenicity of PTC cells invivo was reduced following hsa_circ_0118578 suppression. Additionally, EIF4A3, as an RNA-binding protein, was shown to interact with hsa_circ_0118578 to stabilize its expression in PTC cells. Conclusions: Upregulated hsa_circ_0118578 in PTC interacts with EIF4A3 to exert oncogenic effects by enhancing hsa_circ_0118578 stability, contributing to PTC development. These findings shed light on the oncogenic role of hsa_circ_0118578 in PTC and suggest it as a potential therapeutic target.

Matrine promotes colorectal cancer apoptosis by downregulating shank-associated RH domain interactor expression

BACKGROUND The 5-year survival rate of patients with colorectal cancer (CRC) in China is only 56.9%, highlighting the need for new therapeutic drugs. Previous studies have shown that matrine exhibits antitumor effects by inducing apoptosis. However, the mechanism by which matrine regulates antiapoptotic proteins in CRC remains unclear. AIM To identify apoptotic proteins from proteomics and investigate the role of matrine in impeding CRC apoptosis by regulating these proteins. METHODS Tumor and adjacent normal tissues were collected from 52 patients with CRC who underwent surgery between January and December 2021. Data-independent acquisition quantitative proteomic analysis was performed to identify differentially expressed apoptotic proteins. The selected apoptotic proteins were identified through their association with tumor-node-metastasis (TNM) stage and prognosis, then confirmed by immunohistochemical (IHC) staining in validation cohort. In vitro , the role of matrine or apoptotic proteins on cancer cells were analyzed. RESULTS Compared to normal tissues, 88 anti-apoptotic proteins from proteomic results were selected. Among them, Shank-associated RH domain interactor (SHARPIN) was identified because of its relationship with TNM stage and overall survival in TCGA database. In the IHC-confirmed cohort, SHARPIN was highly expressed in CRC tissues and localized in the cytoplasm. Higher SHARPIN expression was associated with TNM stage, carbohydrate antigen 153 levels, and gross type compared to low expression. SHARPIN knockdown promoted apoptosis, significantly upregulated the expression of Bcl-2 associated agonist of cell death, Bcl-2 associated X protein, caspase 3, and caspase 8, and downregulated B-cell lymphoma-2 (P < 0.05). Importantly, matrine treatment promoted apoptosis and reversed the proliferation, invasion, and migration of CRC cells by repressing SHARPIN. CONCLUSION SHARPIN was identified as an upregulated anti-apoptotic protein in CRC, and matrine exhibited anticancer effects by downregulating its expression. Thus, matrine appears to be a promising drug for CRC.

Predictive values of body mass index, prognostic nutritional index and C-reactive protein to prealbumin ratio for prognosis of patients receiving radical gastrectomy.

we aimed to analyze the predictive values of body mass index (BMI), prognostic nutritional index (PNI) and C-reactive protein to prealbumin ratio (CRP/PA) for the prognosis of patients receiving radical gastrectomy. one hundred patients subjected to radical gastrectomy from August 2015 to January 2018 were enrolled. The cut-off values of BMI, PNI and CRP/PA on the receiver operating characteristic (ROC) curves were obtained and applied to establish a low BMI group (n = 46) and a high BMI group (n = 54), a low PNI group (n = 48) and a high PNI group (n = 52), as well as a low CRP/PA group (n = 57) and a high CRP/PA group (n = 43). through comparing the low BMI group with the high BMI group, there were differences in the tumor diameter, invasion depth, clinical stage, and lymph node metastasis status (p < 0.05). Differences were found in the invasion depth, tumor diameter, lymph node metastasis status, clinical stage, and postoperative adjuvant therapy in the low CRP/PA group compared with the high CRP/PA group (p < 0.05). The survival rate of all patients was 45.00 % (45/100) during the 5 years of follow-up. According to the Kaplan-Meier survival analysis, the low BMI group, low PNI group and high CRP/PA group had significantly reduced overall survival rates in comparison to those of the high BMI group, high PNI group and low CRP/PA group, respectively (p < 0.05). BMI, PNI and CRP/PA have important predictive values for the prognosis of patients undergoing radical gastrectomy.

CT-based delta-radiomics for predicting pathological response to neoadjuvant immunochemotherapy in esophageal squamous cell carcinoma: a multicenter study

BackgroundThe study aimed to investigate the predictive value of delta-radiomics derived from computed tomography (CT) for pathological complete response (pCR) to neoadjuvant immunochemotherapy (NICT) among patients with esophageal squamous cell carcinoma (ESCC), helping clinicians determine whether to modify the neoadjuvant treatment strategy, proceed to surgery, or forgo surgery altogether.MethodsA total of 140 ESCC patients from two institutions (Database 1 = 93; Database 2 = 47) who underwent NICT and surgery were retrospectively included in the study. The training set consisted of patients from Database 1, while the testing set included patients from Database 2. All patients underwent contrast-enhanced CT scans before the start of the treatment and prior to the operation. The delta-radiomics features were calculated as the relative net change of radiomics features between the two-time points. Feature selection was conducted using Pearson correlation analysis, intraclass correlation coefficients, and the fivefold cross-validation with least absolute shrinkage and selection analysis. Four models were established, comprising a clinical model, a pre-treatment radiomics model, a delta-radiomics model, and a mixed model. Area under the curve (AUC) and decision curve analysis were used to assess the performance and the clinical value of the models.ResultsLess than half of the tumors (40/140, 28.6%) showed pCR following NICT. The delta-radiomics model displayed AUC of 0.827 and 0.790 in the training and testing set for predicting pCR, which was superior to the clinical model based on age and clinical tumor node metastasis (cTNM) stage (0.758 and 0.615) and the pre-treatment radiomics model (0.787 and 0.621). Furthermore, the delta-radiomics model demonstrated a more excellent AUC value in the testing set than the mixed model (0.847 and 0.719), which integrated clinical and delta-radiomics features.ConclusionsThe delta-radiomics model exhibited better diagnostic performance in preoperative prediction of pCR for NICT in ESCC patients compared to the clinical, pre-treatment radiomics, and mixed models.

Utility of Serum Lipids and CEA Levels as Novel Markers in Comparison to Various Histopathological Parameters and TNM Staging in Colorectal Carcinoma: A Research Protocol

Introduction: Colorectal Cancer (CRC) is the third most widespread type of cancer around the globe. Elevated Carcinoembryonic Antigen (CEA) levels, a blood protein, are often observed in CRC patients. Need of the Study: Among gastrointestinal cancers, CRC is the most frequent cause of death. This research aims to investigate the potential link between serum lipid profiles, the levels of CEA, and the risk of developing CRC. Early detection and staging of CRC are crucial for effective management and improved outcomes. Aim: To evaluate the efficacy of serum lipids and CEA levels as novel markers compared to different Tumour Node Metastasis (TNM) staging and histopathological parameters in CRC. Materials and Methods: A cross-sectional study will be conducted in the Department of Pathology at Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Sawangi, Wardha, Maharashtra, India from October 2024 to April 2026. Peripheral blood samples will be collected from CRC patients to determine serum lipid profiles and CEA levels. Resected colon specimens will be processed and graded using TNM staging with appropriate staining. Karl Pearson’s test (data distributed normally) or Spearman’s test (data distributed non normally) will be used to conduct a correlation between continuous variables. A p-value of less than 0.05 will be considered statistically significant.

Prognostic Significance of Innovative Inflammation-nutrition Biomarker Score in Patients With Colorectal Cancer.

A new index, inflammation-nutrition biomarker score (INS), based on host factors, including lymphocyte to C-reactive protein ratio, C-reactive protein to albumin ratio, advanced lung cancer inflammation index, and nutritional risk index, correlated with post-operative survival time independent of the tumor, node, metastasis (TNM) stage, in a cohort of patients with various types of malignancies. Therefore, this study aimed to evaluate the prognostic value of INS in patients with colorectal cancer who underwent curative resection. We retrospectively evaluated 476 consecutive patients who underwent curative surgery for stage I-III colorectal cancer. Based on the INS definition, 240, 132, 57, 23, and 24 patients had a score of 0, 1, 2, 3, and 4, respectively. Patients with INS of 0 and 1 were classified into the low-INS group, and those with INS of 2, 3, and 4 were classified into the high-INS group. The relapse-free and overall survival rates were significantly worse in the high-INS group than in the low-INS group. Furthermore, multivariate analysis of the prognostic factors indicated that INS is an independent prognostic factor for poor relapse-free and overall survival. The combined evaluation of INS and TNM stages may allow for more accurate prognostication.

Collagen signature adds prognostically significant information to staging for breast cancer

Tumor-associated collagen signature (TACS) is an independent prognostic factor for breast cancer. However, it is unclear whether the complete collagen signature, including TACS, the TACS-based collagen microscopic features (TCMF1), and the TACS-based nuclear features (TCMF2), can provide additional prognostic information for the current tumor-node-metastasis (TNM) staging system. We included 941 patients with breast cancer from three cohorts: the training (n= 355), internal (n= 334), and external validation cohorts (n= 252). TACS and TCMF1 were obtained by multiphoton microscopy (MPM). TCMF2 was extracted on the hematoxylin and eosin images colocated with MPM images. They were linearly combined to establish a complete collagen signature score for reclassifying current TNM staging into stage Ⅰ (II and Ⅲ)/low risk and stage Ⅰ (II and Ⅲ)/high risk. The low-risk collagen signatures 'downstaged' patients in stage II or Ⅲ, while the high-risk collagen signatures 'upstaged' patients with stage Ⅰ tumors. After incorporating the complete collagen signature into the current TNM staging system, the modified staging system had a higher ability to stratify patients [referent, Ⅰ-new; Ⅱ-new, hazard ratio (HR) 8.655, 6.136, and 4.699 in the training, internal validation, and external validation cohorts, respectively; Ⅲ-new, HR 14.855, 11.201, and 13.245 in the corresponding three cohorts, respectively] than the current TNM staging system (referent, Ⅰ; Ⅱ, HR 1.642, 1.853, and 1.371 in the corresponding three cohorts, respectively; Ⅲ, HR 4.131, 4.283, and 3.711 in the corresponding three cohorts, respectively). Furthermore, the modified staging system showed a higher area under the curve than the current TNM staging system (training cohort: 0.843 versus 0.683; internal validation cohort: 0.792 versus 0.661; and external validation cohort: 0.793 versus 0.646). The complete collagen signature is an independent predictor of survival outcomes in breast cancer. It adds significant information about the biological behavior of the disease to staging for breast cancer.

Role of high-resolution magnetic resonance imaging in preoperative tumor-node-metastasis staging evaluation of esophageal cancer: a narrative review.

Esophageal cancer (EC) is an aggressive disease characterized by high mortality rates and a propensity for locoregional or distant recurrence. The treatment strategies and prognostic estimation for EC depend on accurate pre-treatment tumor-node-metastasis (TNM) staging. The objective of this review was to illustrate the role of various imaging modalities in achieving accurate preoperative TNM staging of EC, with a particular focus on the utilization of advanced high-resolution magnetic resonance imaging (MRI) sequences for T classification, which have shown promise in enhancing the delineation of tumor depth and extent. A comprehensive literature search was conducted in PubMed and Web of Science databases. The studies on imaging in preoperative TNM staging of EC published in English from inception of these databases to December 31, 2022 were reviewed. The review highlights the distinct advantages and inherent limitations of different imaging modalities for the preoperative staging of EC. Endoscopic ultrasound (EUS) provides real-time, high-resolution imaging of the esophageal wall but is operator-dependent. Computed tomography (CT) is widely available and non-invasive, but it may lack sensitivity for early T-stage identification. Positron emission tomography (PET)/CT offers accurate assessment of distant metastasis but has limited value in the evaluation of early-stage tumors. With improved techniques, MRI is particularly useful for visualization of tumor infiltration and the surrounding anatomical structures, gaining prominence in preoperative staging of EC. Various imaging modalities including EUS, CT, PET/CT, and MRI should be applied as complementary methods for preoperative TNM staging of EC. Notably, high-resolution MRI can overcome motion-related artifacts and provide high-quality images, which may play a more important role in the management of EC in the future.

ABALON regulates mitophagy and 5-FU sensitivity in colorectal cancer via PINK1-Parkin pathway.

Growing evidence demonstrated that long non-coding RNAs (lncRNAs) are closely related with chemoresistance in colorectal cancer (CRC). Mitophagy serves as an essential factor to maintain the quality of tumor cells. However, it is unclear whether lncRNAs are involved in mitophagy regulation in CRC. The aim of this study is to evaluate whether lncRNAs are involved in regulating mitophagy and chemoresistance in CRC. In this study, gain/loss of function was used to analyze the biological function influenced by apoptotic BCL2L1-antisense long non-coding RNA (ABALON). Western blot and JC-1 probe were carried out for detecting mitophagy. Chemosensitivity of CRC cells to 5-fluorouracil (5-FU) was determined using cell counting kit-8 (CCK-8), flow cytometry, colony formation and trans well assays. We found that ABALON expression was increased in CRC, especially in consensus molecular subtype 1 (CMS1) and highly expressed ABALON was related with tumor differentiation, tumor node metastasis (TNM) staging, and lymph node metastasis (P<0.05). ABALON knockdown led to impaired proliferation and enhanced apoptosis in CRC. Mitophagy variations primed by ABALON enhanced mitochondrial homeostasis. The half maximal inhibitory concentration (IC50) of 5-FU in ABALON interference groups declined, while ABALON overexpression elevated IC50. Furthermore, defective mitophagy not only rescued the proliferation, metastasis, and apoptosis induced by ABALON overexpression, but also, enhanced the anti-tumor effect of 5-FU in vivo. Collectively, our study proposed that ABALON potentiates CRC progression via PINK1/Parkin mediated mitophagy, and ABALON is a promising therapeutic target in reversing 5-FU resistance.

Clinical significance of tertiary lymphoid structure maturity in colorectal cancer patients.

To explore the clinical significance of the maturation of tertiary lymphoid structures (TLS) in colorectal cancer patients. A total of 230 surgical removed colorectal cancer specimens with detailed follow-up data were collected from Yinzhou Second Hospital. There were 128 cases of mature TLS and 108 cases of immature TLS according to immunohistochemical results. The patient age, gender, maximum tumor diameter, tumor location, differentiation degree, depth of invasion, lymph node metastasis, vascular tumor thrombus, liver metastasis, distant non-liver metastasis, mismatch repair status, expression of Ki-67, P53 and programmed cell death ligand 1 (PD-L1) were analyzed. The Kaplan-Meier method (Breslow test) was used to analyze the survival of patients, and multivariate Cox regression model was applied to analyze the prognostic factors. Compared to the immature TLS group, the mature TLS group showed a significantly lower rate of vascular tumor thrombus, lymph node metastasis, and liver metastasis. Additionally, the positive expression rate of Ki-67 was markedly reduced, while the rate of deficient mismatch repair and the positive expression rate of PD-L1 were significantly increased (all P<0.05). The overall survival rate of the mature TLS group was superior to that of the immature TLS group (Breslow=4.553, P<0.05). Cox regression analysis indicated that lymph node metastasis was an independent risk factor for the prognosis of colorectal cancer patients (P<0.01), while TLS maturation was a protective factor (P<0.05). The formation of TLS may play a significant role in inhibiting lymph node metastasis, liver metastasis, and vascular tumor thrombus in colorectal cancer, and patients with mature TLS have a favorable clinical prognosis, which can provide a reference for the immunotherapy and prognostic assessment of colorectal cancer patients.

Distinct clinical features of urothelial carcinoma with low-expressing human epidermal growth factor receptor 2 status.

Some urothelial carcinoma patients are ineligible for platinum-based chemotherapy, necessitating exploration of other effective therapeutic strategies. Human epidermal growth factor receptor 2 (HER2) protein overexpression, gene amplification or mutations exist in urothelial carcinoma. Our study is to investigate the correlation of three-tier assessment of HER2 expression with clinical pathological characteristics and prognosis of urothelial carcinoma. HER2 expression in 75 urothelial carcinomas from Jiangsu Cancer Hospital was re-scored by immunohistochemistry and fluorescence in situ hybridization according to HER2 three-tier assessment standards. Its relationship with various pathological parameters of urothelial carcinoma and its correlation with prognosis were analyzed. And validate in The Cancer Genome Atlas (TCGA) cohort. HER2 expression was observed in 82.7% (62/75) of urothelial carcinoma patients, of which HER2-low expression accounted for 61.3% (46/75). HER2 expression was significantly correlated with the tumor-nodes-metastasis (TNM) stage of urothelial carcinoma (P=0.043) and HER2-low was an independent poor prognostic factor for patients with urothelial carcinoma (P=0.04). Follow-up showed that HER2-low patients had the worst prognosis compared with HER2-negative (P=0.02) and HER2 positive (P=0.02) and also had the highest progression rate in TCGA cohort (P=0.02); receiver operator characteristic (ROC) model suggested HER2-low could effectively predict prognosis. HER2 expression is closely related to the TNM stage of urothelial carcinoma; HER2 three-tier assessment can effectively predict clinical prognosis of urothelial carcinoma.

Changes in complement C3a in the immunotherapy of advanced clear cell renal cell carcinoma.

Immunotherapy is an emerging treatment modality for clear cell renal cell carcinoma (CCRCC). As a molecule involved in the prognosis of CCRCC, the effect of complement C3a expression levels on immunotherapy is unclear. This study aims to investigate the correlation between C3a and clinicopathological features in early CCRCC, as well as the alterations in complement C3a during immunotherapy for advanced CCRCC and its influence on therapeutic outcomes. Immunohistochemistry was used to detect the expression of complement C3a in newly diagnosed CCRCC tissues and paracancerous tissues. The peripheral serum of advanced CCRCC patients who underwent programmed cell death protein 1 (PD-1) antibody immunotherapy was collected before treatment and after four cycles of treatment, and detected by enzyme-linked immunosorbent assay. For the concentration of complement C3a, the Response Evaluation Criteria in Solid Tumors version 1.1 was used to evaluate the therapeutic effect. Of the 110 CCRCC cases, 76 (69.09%) were positive for C3a expression, showing brown staining in the cytoplasm and membrane of the tumor cells. No difference was observed in the expression of complement C3a in the tumor tissues in terms of gender, age, location, and histological grade. The expression of complement C3a in tumors with a maximum transverse diameter >3.5 cm was higher than that in tumors with a maximum transverse diameter ≤3.5 cm (P=0.02), and the expression of complement C3a in the tissues of the tumor node metastasis classification (TNM) stage II patients was higher than that of the TNM stage I patients (P=0.005). Among the 30 patients with advanced CCRCC who underwent immunotherapy, 12 had a complete response (CR) or a partial response (PR), 7 had stable disease (SD), and 11 had progressive disease (PD). The C3a concentration decreased in the CR + PR + SD group after treatment, while it increased in the PD group and the difference was statistically significant. The survival analysis indicated that the progression-free survival of patients with decreased complement C3a after treatment was longer than that of patients with increased C3a (P<0.001). Complement C3a is highly expressed in CCRCC, and the high expression of complement C3a is related to the stage and tumor size. During immunotherapy for CCRCC, changes in complement C3a can reflect the curative effect to a certain extent.

Unlocking the diagnostic potential of vascular endothelial growth factor and interleukin-17: Advancing early detection strategies for hepatocellular carcinoma.

Tian et al investigated the diagnostic value of serum vascular endothelial growth factor (VEGF) and interleukin-17 (IL-17) in primary hepatocellular carcinoma (PHC). Their retrospective study, published in the World Journal of Gastrointestinal Surgery, revealed that the serum levels of VEGF and IL-17 are significantly elevated in PHC patients compared with healthy controls. These biomarkers are closely associated with pathological features such as tumor metastasis and clinical tumor node metastasis stage. A receiver operating characteristic analysis further confirmed the diagnostic efficacy thereof, suggesting that VEGF and IL-17 could serve as valuable tools for early detection and treatment guidance. This study underscores the potential of integrating these biomarkers into clinical practice to increase diagnostic accuracy and improve patient management in PHC.

The impact of positive resection margin in perihilar cholangiocarcinoma, ductal margin vs radial margin.

Resection margin status is the important prognostic factor in resected perihilar cholangiocarcinoma (pCCA). Although the impact of ductal margin (DM) was reported in many studies, the influence of radial margin (RM) is unclear. This study aims to investigate the effect of positive RM on survival. Patients with pCCA underwent curative resection between 2013 and 2018 were retrospectively reviewed. Resection margin status was divided into negative resection margin (R0) and positive resection margin (R1); positive RM alone (RM+) and positive DM with or without positive RM (DM+). Of the 167 pCCA patients, 62 (37.1%) had R1 margin. Among 62 R1 patients; 17 (27.4%) had positive DM alone, 20 (32.3%) had positive RM alone and 25 (40.3%) had both positive DM and RM. The R1 patients had a significantly greater number of lymph node metastasis (LNM) and advanced tumor staging than R0 patients, however there was no difference between the RM + and DM + patients. The median survival time of patients with RM + was significantly poorer than R0 patients (13.8 vs. 24.5 months; p < 0.001, respectively) and similar to the DM + patients (9.1 months, p = 0.556). However, in patients with LNM, those who underwent R0 resection had no statistically significant difference in survival outcomes compared to those with R1 resection. Positive resection margin remains the important prognostic factor, and positive RM is common in these patients. Positive RM also had a comparable effect on survival as positive DM. As a result, in pCCA, surgical resection should target both RM and DM.

Analysis of therapeutic effects and influencing factors of ICIs in lung-cancer patients.

The aim of this retrospective study was to analyze the efficacy and risk factors of immune checkpoint inhibitors (ICIs) in lung cancer patients. One hundred lung cancer patients who were treated in our hospital from May 2021 to May 2023 were selected as the study subjects and divided into chemotherapy group (n = 50) and ICIs group (n = 50), in which the chemotherapy group was given the combined treatment of vincristine and cisplatin (NP), while the ICIs group was given ICIs for treatment. The therapeutic effect and adverse reactions (hypertriglyceridemia, anemia, hypertension and hypoproteinemia) of the two groups were compared, and fasting venous blood was collected. The levels of carcinoembryonic antigen (CEA) and cancer antigen 199 (CA199) were compared between the two groups before and after treatment. According to the therapeutic effect, 100 patients with lung cancer were divided into complete remission (CR) + partial remission (PR) group (n = 52) and stable (SD) + progressive (PD) group (n = 48). The clinical data and pathologic data of the two groups were compared. The rates of objective effective rate (ORR) in chemotherapy group and ICIs group were 36.00% and 68.00% respectively, and the level of ORR in ICIs group was significantly higher than that in chemotherapy group, with statistical significance (P < 0.05). There was no significant difference in serum CEA and CA199 levels between the two groups before operation (P > 0.05). Three months after operation, the serum CEA and CA199 levels in ICIs group were significantly lower than those in chemotherapy group, and the difference was statistically significant (P < 0.05). The adverse reactions of hypertriglyceridemia, anemia, hypertension and hypoproteinemia in chemotherapy group and ICIs group during treatment were all grade 1-2, and the incidence of adverse reactions was similar between the two groups (P > 0.05). There was no significant difference in sex, age, anatomic position, pathologic type, smoking history and differentiation between the two groups (P > 0.05). In SD + PD group, the preoperative maximum tumor diameter > 4cm, tumor node metastasis (TNM) stage IV, lactate dehydrogenase (LDH) ≥ 183 U/L, and tumor volume ≥ 120m3 were significantly higher than those in CR + PR group, and the prognostic nutritional index (PNI) ≥ 41.8 and the proportion of ICIs were significantly lower than those in CR + PR group, with statistical significance (P < 0.05). Multifactorial logistic regression analysis showed that preoperative maximum tumor diameter > 4cm and LDH ≥ 183U/L were risk factors for poor lung cancer outcome, and PNI ≥ 41.8 and ICIs treatment were protective factors for poor lung cancer outcome (P < 0.05). ICIs is effective in the treatment of lung cancer, which can obviously reduce the tumor load and has high safety. In addition, the maximum tumor diameter and LDH are risk factors that affect the poor curative effect of lung cancer. High PNI level and ICIs treatment are helpful to improve the effect of lung cancer, and early monitoring is helpful to guide the treatment plan and evaluate the treatment effect.

In-depth analysis of lymph node metastasis-related sialylated protein profiling and their clinical and biological significance in colorectal cancer using mass spectrometry and multi-omics technologies

Colorectal cancer (CRC) lymph node metastasis (LNM) is a crucial factor affecting the prognosis and treatment outcomes of CRC patients. It has been confirmed that altered glycosylation is a key event during CRC lymphatic metastases. Sialylation is one of the most significant glycosylation alterations in tumors. However, the predictive role of sialylation and sialylated protein in CRC remains elusive, especially in CRC-LNM. In this study, we explored and identified 1102 sialylated glycoproteins in CRC-LNM using metabolic labeling strategy and proteomics analysis. Combined with comprehensive analysis with bioinformatics and machine learning algorithms, we screened 25 prognostic sialylation-related genes (SRGs) to construct a new molecular phenotype (LRSRGs-Phenotype) and a prognostic SRG signature (LRSRGs-related Gene Signature) in CRC. Then, we further confirmed that patients in different phenotypes had different prognosis, molecular biological characteristics, immune cell infiltration and could be closely linked to three previously reported immune phenotypes: immune-excluded (Phenotype A), immune-desert (Phenotype B), and immune-inflamed (Phenotype C). Besides, we evaluated and validated the LRSRGs-related gene (ACADM, EHD4, FLOT1, GPC1, GSR, LRRC8A, NGFR, SDHB, and SEC61G) signature and found the risk score was an independent risk factor for CRC prognosis. CRC patients in different risk groups had different somatic mutation, tumor microenvironment and immunotherapy response. Finally, we also identified the potential therapeutic agents for CRC patients in different risk groups. In conclusion, we explored the key sialylated glycoproteins, which may play a key role in tumor LNM and clinical outcomes. And constructed the LRSRGs-phenotype and signature with prognostic and therapeutic predictive value in CRC, hoping to provide reliable scientific basis for future treatments in CRC patients.

Comparative evaluation of low and high radioiodine doses in differentiated thyroid carcinoma management: A multicenter study

Iodine-131 (131I) therapy plays a crucial role in the ablation of thyroid remnants in differentiated thyroid cancer (DTC), although there remains ongoing debate concerning the appropriate dosage. This study aims to compare the effects of low and high doses of radioiodine (RAI) in the management of DTC. For this purpose, 100 adult patients with verified DTC histology who had either total or nearly total thyroidectomy were injected with either 1.1 GBq (30 mCi) or 3.7 GBq (100 mCi) of radioiodine (131I). Those patients were categorized as low or intermediate risk following the American Thyroid Association (ATA) recommendations. Retrospective data was manipulated from multiple center units nuclear medicine in Saudi Arabia on equal numbers of selected male and female patients, with ages in the range from 20 to 66 years with an average of 40.72 ± 11.49. According to the tumour-node-metastasis (TNM) classification, the most tumours (T) stages in both groups were T1 or T2, with 80% in the high-dose group and 86% in the low-dose group. After the radioiodine therapy (RIT), the thyroglobulin (Tg) levels were below 10 ng/ml across both groups (72 % in the high-dose group and 66 % in the low-dose group). There was no discernible therapeutic distinction between patients with low and moderate risks in terms of treatment efficacy. The results revealed that the RIT with a low-dose ablation success rate (78%) is almost the same as the high-dose ablation success rate (82%). Therefore, this indicates that both the low and high-dose ablation effectively reduce Tg levels and achieve successful ablation.

Clustering of gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) using machine learning (ML) and comparison with Tumour, Node, Metastasis (TNM) staging: a retrospective, population-based study using Surveillance, Epidemiology, and end results (SEER)

Clustering of gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) using machine learning (ML) and comparison with Tumour, Node, Metastasis (TNM) staging: a retrospective, population-based study using Surveillance, Epidemiology, and end results (SEER)

Serum LINC01133 combined with CEA and CA19-9 contributes to the diagnosis and survival prognosis of gastric cancer.

Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are currently 2 major diagnostic biomarkers for gastric cancer (GC). The aims of study were to detect the expression of long intergenic nonprotein coding RNA 1133 (LINC01133), and to evaluate its diagnostic and prognostic value in GC. Furthermore, the clinical performance of the joint detection of LINC01133, CEA and CA19-9 was also evaluate in GC. The data were collected from 156 GC, 96 chronic superficial gastritis, 77 chronic atrophic gastritis patients and 89 healthy controls. LINC01133 expression was determined by quantitative real-time PCR. Receiver operating characteristics analysis was used to evaluate the diagnostic value of LINC01133, CEA, CA19-9 individually and jointly. Kaplan-Meier method and log-rank test were used to conduct survival comparison analysis. Cox regression was used to screen the independent prognostic factors for GC. Serum LINC01133 expression was decreased in GC patients compared with chronic superficial gastritis, chronic atrophic gastritis and healthy controls, and had considerable diagnostic potential, and notably, the joint detection of LINC01133, CEA, and CA19-9 showed the highest diagnostic accuracy in distinguishing GC patients from healthy or gastritis patients. LINC01133 expression was associated with GC patients' CEA and CA19-9 levels, tumor size, differentiation, lymph node metastasis and tumor node metastasis stage. Low LINC01133 was associated with poor GC survival, and was an independent prognostic factor for GC. Decreased serum LINC01133 had considerable diagnostic potential, and the joint detection of LINC01133, CEA, and CA19-9 might be a more efficient diagnostic strategy for GC patients. Reduced LINC01133 served as a prognostic biomarker to predict poor GC survival.