Independent Prognostic Factor Research Articles

Fibrinogen-to-albumin ratio (FAR) is the best biomarker for the overall survival of patients with non-small-cell lung cancer.

The inflammatory response and the nutritional status are associated with overall survival (OS) in patients with non-small cell lung cancer (NSCLC), but it is unclear which biomarkers are better suited to predict prognosis. This study sought to determine which of the commonly existing inflammatory and nutritional indicators best predicted the OS. This study included 15 compound indicators based on inflammation or nutrition, with cutoff points obtained through the receiver operating characteristic (ROC) curve. Univariate and multivariate Cox proportional risk models were used to evaluate the relationship between these predictors and OS. Kaplan-Meier curves were used for survival analysis, and log-rank tests were used to compare differences between groups. The C-index was calculated to evaluate the predictive ability of the different indicators. The study included 899 patients with NSCLC. In the univariate analysis, all 15 measures were significantly associated with the OS of patients (all p < 0.05). The results of the C-index analysis showed that the fibrinogen-to-albumin ratio (FAR), the systemic immune-inflammation index (SII), and the albumin-to-alkaline phosphatase ratio (AAPR) were the three indices with the best predictive performance. Among them, FAR (C-index = 0.639) had the best predictive power for OS in patients with NSCLC. In the different subgroups, FAR had the highest C-index in male, non-smoking, adenocarcinoma, and stage II patients. The C-index of the platelet-to-lymphocyte ratio (PLR) in female patients was the highest. SII was the highest in smokers, in those aged <65 and ≥65 years, and in stage III patients. The C-index of AAPR was the highest in non-adenocarcinomas. The C-index of the pan-immune-inflammation value (PIV) was the highest in stage I patients. In the multivariate Cox regression analysis, among FAR, SII, and AAPR, only FAR was an independent predictor of OS in patients with NSCLC. A high FAR was associated with a higher risk of death in patients with NSCLC (HR = 1.601, 95% CI = 1.028-2.495). In order to further evaluate the potential prognostic value of FAR, SII, and AAPR in patients with different stages, Cox regression analysis was performed for those with stage I-II and stage III NSCLC. The results showed that FAR was an independent prognostic factor for OS in patients with stage I-II NSCLC. For all patients with NSCLC, the prognostic power of FAR was superior to that of other inflammatory and nutritional indicators.

Prognostic Value of NLR, PLR, SII, and dNLR in Urothelial Bladder Cancer Following Radical Cystectomy

BackgroundInflammation plays a crucial role in tumor development and progression, with inflammatory markers showing promise in predicting cancer prognosis. However, their significance in muscle-invasive bladder cancer (MIBC), especially in the context of neoadjuvant chemotherapy (NAC), remains poorly understood. This study aims to evaluate the prognostic utility of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune inflammation index (SII), and derived neutrophil-to-lymphocyte ratio (dNLR) for overall survival (OS) in bladder cancer (BC) patients undergoing radical cystectomy (RC) in the NAC era. Patients and MethodsA retrospective review analyzed prospectively-collected data from our institutional BC registry, covering patients with MIBC undergoing RC with curative intent from March 1st, 2016, to December 31st, 2022. Blood samples were collected preoperatively to calculate NLR, PLR, SII, and dNLR. OS was defined from surgery to last follow-up or death. Statistical analyses included ROC curves, Kaplan-Meier Curves, and Cox proportional hazards regression models. ResultsA total of 187 patients with median duration follow-up of 14.7 month were included in this study and 50.8% experienced death. NAC was administered in 50.3% of cases. The ideal cut-off for dichotomizing NLR, PLR, SII, and dNLR was 1.76, 104.30, 410.66, and 1.30, respectively. In multivariable analysis each of these biomarkers emerged as an independent prognostic factor for predicting OS. The results showed a correlation between higher NLR, PLR, SII, and dNLR levels and a deterioration in OS. ConclusionElevated values of these inflammatory markers indicate poorer survival, highlighting their potential as indicators of disease aggressiveness. Identifying patients with elevated markers can help healthcare providers personalize treatment strategies, improving patient outcomes and survival rates.

Clinical value of measuring plasma D-dimer levels in patients with esophageal cancer

BackgroundEsophageal cancer represents a significant public health concern; however, reliable diagnostic and prognostic markers have not been established. This study aimed to investigate the clinical value of plasma D-dimer levels in patients with esophageal cancer.MethodsOverall, 120 patients with esophageal cancer who underwent radical surgical resection at our department between January 2019 and 2020 were included (esophageal cancer group). Plasma D-dimer levels were measured preoperatively and on postoperative days 1 and 14. Additionally, 60 healthy participants (control group) with measured plasma D-dimer levels were included. The preoperative D-dimer levels and positive D-dimer test rates were compared between the groups. The 3-year survival rate in patients with esophageal cancer was calculated using the Kaplan–Meier method.ResultsPreoperative D-dimer concentration in the esophageal cancer group was (0.65 ± 0.859 µg/mL) significantly higher than that in the control group (0.32 ± 0.369 µg/mL). The positivity rate in the esophageal cancer group (35.0%, 42/120) was significantly higher than that in the control group (15%, 9/60). D-dimer concentrations were significantly higher 1 day postoperatively than preoperatively. Conversely, D-dimer concentrations were significantly lower 14 days postoperatively than preoperatively. Patients in the esophageal cancer group with plasma D-dimer concentrations ≤ 0.5 µg/mL had significantly higher 3-year survival rates than those with higher concentrations. In the logistic multivariate analysis, tumor pathological stage and preoperative plasma D-dimer levels were independent prognostic factors of 3-year survival rates in patients with esophageal cancer.ConclusionPlasma D-dimer concentrations are clinically valuable in esophageal cancer diagnosis, postoperative recurrence monitoring, and prognosis prediction.

Prognosis of isolated locoregional recurrence after early breast cancer with immediate breast reconstruction surgery: a retrospective multi‑institutional study.

The prognosis in patients with breast cancer with isolated locoregional recurrence (ILRR) without simultaneous distant metastases after immediate breast reconstruction (IBR) remains unknown. We aimed to investigate the prognosis in this patient population. This multi-institutional retrospective observational study evaluated 3295 patients with primary breast cancer who underwent IBR at 12 Japanese medical facilities between January 1, 2008 and December 31, 2016. The outcome measures were the prognostic factors for ILRR after IBR, 5-year distant metastasis-free interval (DMFI), and 5-year overall survival (OS). Mastectomy or skin-sparing mastectomy was performed in 3295 patients. ILRR occurred in 70 patients, and the median observation period from ILRR diagnosis was 39.3months. Of the 70 patients, 9 (12.9%) had axillary lymph node recurrence (ALNR) at the time of ILRR diagnosis. The 5-year DMFI and OS rates after ILRR were 92.4% and 91.2%, respectively. Pathological lymph node metastasis at primary surgery (P = 0.041) and ALNR (P = 0.022) at ILRR were significantly associated with DMFI in the univariate analysis. ALNR was the only independent prognostic factor in the multivariate analysis (P = 0.041). Post-mastectomy radiation therapy (PMRT; P = 0.022) and ALNR (P = 0.043) were significantly associated with OS in the univariate analysis, and both PMRT (P = 0.010) and ALNR (P = 0.028) were independent prognostic factors in the multivariate analysis for OS. Although patients with breast cancer who had ILRR after IBR have favorable prognosis, ALNR may lead to poor prognosis. To the best of our knowledge, this study is the first to report the prognosis of these patients.

Quantifying spatial CXCL9 distribution with image analysis predicts improved prognosis of triple-negative breast cancer.

Background: The C-X-C motif chemokine ligand 9 (CXCL9) plays a pivotal role in tumor immunity by recruiting and activating immune cells. However, the relationship between CXCL9 expression and prognosis in triple-negative breast cancer (TNBC) is unclear. Methods: We investigated CXCL9 mRNA expression, clinicopathological features, and prognosis in TNBC patients. We also used computational image analysis to quantify and assess the distribution of CXCL9 protein in the tumor core (TC) and invasive margin (IM). Results: CXCL9 mRNA expression was significantly higher in TNBC tumors compared to normal tissue (p < 0.001) and was associated with smaller tumors (p = 0.022) and earlier stages (p = 0.033). High CXCL9 mRNA expression was correlated with improved overall survival (OS) in three independent cohorts (all p < 0.05). In a separate analysis, low CXCL9 protein expression was associated with increased lymph node metastasis (p = 0.018 and p = 0.036). High CXCL9 protein expression in the TC, IM, or both was associated with prolonged OS (all p < 0.001). Conclusion: High CXCL9 expression, at both the mRNA and protein levels, is associated with improved prognosis in TNBC patients. CXCL9 expression in the TC and/or IM may be an independent prognostic factor.

Effectiveness of immune checkpoint inhibitor therapy on bone metastases in non-small-cell lung cancer.

Bone metastases (BoMs) are prevalent in patients with metastatic non-small-cell lung cancer (NSCLC) however, there are limited data detailing how BoMs respond to immune checkpoint inhibitors (ICIs). The purpose of this study was to compare the imaging response to ICIs of BoMs against visceral metastases and to evaluate the effect of BoMs on survival. A retrospective, multicentre cohort study was conducted in patients with NSCLC treated with nivolumab or pembrolizumab in Alberta, Canada from 2015 to 2020. The primary endpoint was the real-world organ specific progression free survival (osPFS) of bone versus visceral metastases. Visceral metastases were categorized as adrenal, brain, liver, lung, lymph node, or other intra-abdominal lesions. The secondary outcome was overall survival (OS) amongst patients with and without BoMs. A total of 573 patients were included of which all patients had visceral metastases and 243 patients (42.4%) had BoMs. High PD-L1 expression was identified in 268 patients (46.8%). No significant difference in osPFS was observed between bone, liver, and intra-abdominal metastases (p=0.20 and p=0.76, respectively), with all showing shorter osPFS than other disease sites. There was no difference in the osPFS of extra-thoracic sites of disease in patients with high PD-L1 expression. There was significant discordance between visceral disease response and bone disease response to ICI (p=0.047). The presence of BoMs was an independent poor prognostic factor for OS (HR 1.26, 95%CI: 1.05-1.53, p=0.01). Metastatic bone, liver, and intra-abdominal lesions demonstrated inferior clinical responses to ICI relative to other sites of disease. Additionally, the presence of bone and liver metastases were independent poor prognostic factors for overall survival. This real-world data suggests that BoMs respond poorly to ICI and may require treatment adjuncts for disease control.

Establishment and validation of a bad outcomes prediction model based on EEG and clinical parameters in prolonged disorder of consciousness.

This study aimed to explore the electroencephalogram (EEG) indicators and clinical factors that may lead to poor prognosis in patients with prolonged disorder of consciousness (pDOC), and establish and verify a clinical predictive model based on these factors. This study included 134 patients suffering from prolonged disorder of consciousness enrolled in our department of neurosurgery. We collected the data of sex, age, etiology, coma recovery scales (CRS-R) score, complications, blood routine, liver function, coagulation and other laboratory tests, resting EEG data and follow-up after discharge. These patients were divided into two groups: training set (n = 107) and verification set (n = 27). These patients were divided into a training set of 107 and a validation set of 27 for this study. Univariate and multivariate regression analysis were used to determine the factors affecting the poor prognosis of pDOC and to establish nomogram model. We use the receiver operating characteristic (ROC) and calibration curves to quantitatively test the effectiveness of the training set and the verification set. In order to further verify the clinical practical value of the model, we use decision curve analysis (DCA) to evaluate the model. The results from univariate and multivariate logistic regression analyses suggested that an increased frequency of occurrence microstate A, reduced CRS-R scores at the time of admission, the presence of episodes associated with paroxysmal sympathetic hyperactivity (PSH), and decreased fibrinogen levels all function as independent prognostic factors. These factors were used to construct the nomogram. The training and verification sets had areas under the curve of 0.854 and 0.920, respectively. Calibration curves and DCA demonstrated good model performance and significant clinical benefits in both sets. This study is based on the use of clinically available and low-cost clinical indicators combined with EEG to construct a highly applicable and accurate model for predicting the adverse prognosis of patients with prolonged disorder of consciousness. It provides an objective and reliable tool for clinicians to evaluate the prognosis of prolonged disorder of consciousness, and helps clinicians to provide personalized clinical care and decision-making for patients with prolonged disorder of consciousness and their families.

Tumor budding is a meaningful prognostic marker in patients with hepatocellular carcinoma after curative hepatectomy

AbstractAimTumor budding (TB) has excellent prognostic value in many solid tumors, but there is little research on it in hepatocellular carcinoma (HCC). This study assessed the prognostic value of TB in patients with HCC who received hepatectomy.MethodsThis retrospective study included 210 patients with HCC who received curative hepatectomy at the First Affiliated Hospital of Xi'an Jiaotong University, between 2016 and 2018. TB was evaluated on hematoxylin‐ and eosin‐stained slides according to the criteria established by the 2016 International Tumor Budding Consensus Conference. t‐tests, Chi‐squared tests, and rank‐sum tests were used to correlate the extent of TB with clinicopathological parameters. Prognostic analysis was performed using Cox regression models and the Kaplan–Meier method.ResultsThe positive detection rate of TB was 45.2% (95/210) in 210 patients with HCC. Patients positive for TB always exhibit lower tumor differentiation, higher hepatitis B virus DNA levels, and more severe liver fibrosis. Multivariate Cox analysis identified TB (hazard ratio [HR]: 2.232, 95% confidence interval [CI]: 1.479–3.368, p &lt; 0.001) as an independent prognostic factor for patients' recurrence‐free survival (RFS), similar to tumor size (HR: 1.070, 95% CI: 1.070–1.142, p = 0.042) and satellite nodule (HR: 2.266, 95% CI: 1.298–3.956, p = 0.004). Kaplan–Meier analysis also demonstrated that TB‐positive patients had a significantly worse RFS. Interestingly, subgroup analysis revealed that among HCC patients with negative microvascular invasion (MVI), TB was also strongly associated with RFS (HR: 3.206, 95% CI: 1.667–6.168, p &lt; 0.001). These findings suggest that TB may serve as a supplemental prognostic biomarker for HCC‐negative MVI.ConclusionsTB is an adverse prognostic biomarker for HCC, particularly in patients negative for MVI. TB evaluation should be considered in the postoperative pathological examination of HCC in clinical practice.

Should new organ involvement be included in Response Evaluation Criteria in PSMA Imaging?

The current study is intended to investigate the effect of new organ involvement on overall survival (OS) and modify the Response Evaluation Criteria in PSMA Imaging (RECIP) by including new organ involvement to RECIP 1.0. This retrospective study includes 114 patients diagnosed with metastatic castration-resistant prostate cancer (mCRPC) between September 2017 and June 2022 who had received docetaxel treatment and had baseline and post-treatment prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) images. The inclusion criteria were patients with pre- and post-treatment [18F]FDG PET/CT images and whose [18F]FDG PET images were negative. Those whose data were unavailable, who had additional malignancy, or who received abiraterone, enzalutamide, or Lutetium (Lu)-177 treatment were excluded. Age, Gleason score (GS), TPSA (total prostate-specific antigen) levels, surgical history, and OS information were recorded for each patient. The 114 patients herein had a median age of 72.5 (51-91) years and a median GS of 8 (7-10). New lesions were observed in 59 patients (51.7%) and new organ PSMA uptake was observed in 14 patients (12.2%). In the multivariate Cox regression analysis, volume-based treatment response (vTR)-total lesion PSMA (TLP), RECIP PSMA-VOL, modified RECIP (mRECIP) PSMA-VOL, and mRECIP TLP were independent prognostic factors for mortality (p < 0.001, p = 0.006, p = 0.003, and p = 0.003, respectively). The median OS of patients with new organ involvement and new lesion with PSMA uptake was 9.3months (95% CI 2.1-16.5months) and 11.8months (95% CI 7.4-16.2months), respectively. The study concluded that new organ involvement had a shorter OS than new lesion involvement. In the mRECIP that we developed, unlike RECIP, we demonstrated that both PSMA-VOL and TLP value were independent prognostic factors for mortality.

Development of a novel staging classification for Siewert II adenocarcinoma of the esophagogastric junction after neoadjuvant chemotherapy.

Stage classification for Siewert II adenocarcinoma of the esophagogastric junction (AEG) treated with neoadjuvant chemotherapy (NAC) has not been established. To investigate the optimal stage classification for Siewert II AEG with NAC. A nomogram was established based on Cox regression model that analyzed variables associated with overall survival (OS) and disease-specific survival (DSS). The nomogram performance in terms of discrimination and calibration ability was evaluated using the likelihood-ratio test, Akaike information criterion, Harrell concordance index, time-receiver operating characteristic curve, and decision curve analysis. Data from 725 patients with Siewert type II AEG who underwent neoadjuvant therapy and gastrectomy were obtained from the Surveillance, Epidemiology, and End Results database. Univariate and multivariate analyses revealed that sex, marital status, race, ypT stage, and ypN stage were independent prognostic factors of OS, whereas sex, race, ypT stage, and ypN stage were independent prognostic factors for DSS. These factors were incorporated into the OS and DSS nomograms. Our novel nomogram model performed better in terms of OS and DSS prediction compared to the 8th American Joint Committee of Cancer pathological staging system for esophageal and gastric cancer. Finally, a user-friendly web application was developed for clinical use. The nomogram established specifically for patients with Siewert type II AEG receiving NAC demonstrated good prognostic performance. Validation using external data is warranted before its widespread clinical application.

Epidemiology and prognostic nomogram for locally advanced gastric signet ring cell carcinoma: A population-based study.

Gastric signet ring cell carcinoma (GSRC) represents a specific subtype of gastric cancer renowned for its contentious epidemiological features, treatment principles, and prognostic factors. To investigate the epidemiology of GSRC and establish an improved model for predicting the prognosis of patients with locally advanced GSRC (LAGSRC) after surgery. The annual rates of GSRC incidence and mortality, covering the years 1975 to 2019, were extracted from the Surveillance, Epidemiology, and End Results (SEER) database to explore the temporal trends in both disease incidence and mortality rates using Joinpoint software. The clinical data of 3793 postoperative LAGSRC patients were collected from the SEER database for the analysis of survival rates. The Cox regression model was used to explore the independent prognostic factors for overall survival (OS). The risk factors extracted were used to establish a prognostic nomogram. The overall incidence of GSRC increased dramatically between 1975 and 1998, followed by a significant downward trend in incidence after 1998. In recent years, there has been a similarly optimistic trend in GSRC mortality rates. The trend in GSRC showed discrepancies based on age and sex. Receiver operating characteristic curves, calibration curves, and decision curve analysis for 1-year, 3-year, and 5-year OS demonstrated the high discriminative ability and clinical utility of this nomogram. The area under the curve indicated that the performance of the new model outperformed that of the pathological staging system. The model we established can aid clinicians in the early prognostication of LAGSRC patients, resulting in improved clinical outcomes by modifying management strategies and patient health care.

Novel prognostic nomograms for postoperative patients with oral cavity squamous cell carcinoma in the central region of China

BackgroundOral cavity squamous cell carcinoma (OCSCC) is the most common pathological type in oral tumors. This study intends to construct a novel prognostic nomogram model based on China populations for these resectable OCSCC patients, and then validate these nomograms.MethodsA total of 607 postoperative patients with OCSCC diagnosed between June 2012 and June 2018 were obtained from two tertiary medical institutions in Xinxiang and Zhengzhou. Then, 70% of all the cases were randomly assigned to the training group and the rest to the validation group. The endpoint time was defined as overall survival (OS) and disease-free survival (DFS). The nomograms for predicting the 3-, and 5-year OS and DFS in postoperative OCSCC patients were established based on the independent prognostic factors, which were identified by the univariate analysis and multivariate analysis. A series of indexes were utilized to assess the performance and net benefit of these two newly constructed nomograms. Finally, the discrimination capability of OS and DFS was compared between the new risk stratification and the American Joint Committee on Cancer (AJCC) stage by Kaplan-Meier curves.Results607 postoperative patients with OCSCC were selected and randomly assigned to the training cohort (n = 425) and validation cohort (n = 182). The nomograms for predicting OS and DFS in postoperative OCSCC patients had been established based on the independent prognostic factors. Moreover, dynamic nomograms were also established for more convenient clinical application. The C-index for predicting OS and DFS were 0.691, 0.674 in the training group, and 0.722, 0.680 in the validation group, respectively. Besides, the calibration curve displayed good consistency between the predicted survival probability and actual observations. Finally, the excellent performance of these two nomograms was verified by the NRI, IDI, and DCA curves in comparison to the AJCC stage system.ConclusionThe newly established and validated nomograms for predicting OS and DFS in postoperative patients with OCSCC perform well, which can be helpful for clinicians and contribute to clinical decision-making.

Prevalence and survival implications of malnutrition and sarcopenia in metastatic breast cancer: A longitudinal analysis

BackgroundMalnutrition and sarcopenia are challenges for patients with metastatic breast cancer and have been proposed as independent prognostic factors. Very few studies have addressed the temporal evolution of these parameters and, notably, the separate and combined analysis of sarcopenia and malnutrition. This study aimed to i) determine the prevalence of malnutrition and sarcopenia, individually and combined, and their evolution over time, ii) identify risk factors for each condition, and iii) explore their impact on overall survival (OS). MethodsThis retrospective study was conducted on 111 patients treated for at least a third-line metastatic breast cancer at the Institut Curie between January 1st and March 31st, 2018.Solitary malnutrition was defined from weight loss and body mass index values while solitary sarcopenia was defined solely based on low muscle mass. We analyzed solitary malnutrition, solitary sarcopenia, and then malnutrition with or without sarcopenia, at three key stages (T1: diagnosis of metastasis, T2: initiation of third-line treatment, and T3: 3-month re-evaluation). Univariate and multivariate logistic regression analyses were conducted to investigate the risk factors. We performed Cox proportional hazards analyses for each variable. ResultsAt T1, the prevalence of solitary malnutrition, solitary sarcopenia and malnutrition with or without sarcopenia was 18.6%, 36.1% and 48.9% respectively, increasing to 27.7%, 45.5% and 56.6% at T2. At T2, in multivariate logistic regression analyses, patients aged over 60 years were at an elevated risk of experiencing solitary malnutrition as well as malnutrition with or without sarcopenia, but not solitary sarcopenia. In multivariate analyses, solitary malnutrition was significantly associated with poorer OS (HR 2.2 [95% CI 1.1-4.1], p=0.02), while solitary sarcopenia and malnutrition with or without sarcopenia showed no association. ConclusionSolitary malnutrition and sarcopenia were highly prevalent in patients with metastatic breast cancer, affecting around a quarter and half of patients respectively at third-line treatment initiation. Notably, solitary malnutrition emerged as a prognostic factor for overall survival, whereas no significant association was observed for solitary sarcopenia or malnutrition with or without sarcopenia. This highlights the critical need for early identification of patients at risk of malnutrition and the importance of timely intervention.

Impact of red blood cell distribution width (RDW) on postoperative outcomes in hepatocellular carcinoma (HCC) patients.

This study examines the relationship between red blood cell distribution width (RDW) and the prognosis of patients undergoing hepatectomy for hepatocellular carcinoma (HCC). Additionally, it explores the potential effect of RDW for the early identification of high-risk patients after surgery, advocating for timely interventions to improve outcomes. A comprehensive literature search was conducted on May 16, 2022, across PubMed (23 studies), Embase (45 studies), the Cochrane Library (1 study), and CNKI (17 studies), resulting in 6 relevant articles after screening. This analysis primarily focused on the postoperative outcomes of patients. Hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled to assess prognosis, with survival indicators including overall survival (OS) and disease-free survival (DFS). All 6 studies reported on OS, and 2 addressed DFS. A total of 1645 patients from 6 studies were included. The pooled analysis revealed that RDW is an independent prognostic factor for both OS (HR = 1.50, I² = 84%, 95% CI = 1.23-1.77, P < .01) and DFS (HR = 2.06, I² = 15%, 95% CI = 1.51-2.82, P < .01). Patients in the high RDW group exhibited significantly poorer OS and DFS compared to those in the low RDW group. RDW is a prognostic factor for HCC patients after surgery. Elevated RDW levels are associated with a poorer prognosis, adversely affecting both OS and DFS. RDW may serve as a valuable marker for stratifying risk and guiding intervention strategies in the postoperative management of HCC patients.

An immune-related eleven-RNA signature-drived risk score model for prognosis of osteosarcoma metastasis

This study aimed to determine an immune-related RNA signature as a prognostic marker, in this study, we developed a risk score model for predicting the prognosis of osteosarcoma metastasis. We first downloaded the clinical information and expression data of osteosarcoma samples from the UCSC Xena and GEO databases, of which the former was the training set and the latter was the validation set. Immune infiltration was assessed using the ssGSEA and ESTIMATE algorithms, and the osteosarcoma samples were divided into the Immunity_L and Immunity_H groups. Then, eleven RNAs were identified as the optimal prognostic RNA signatures using LASSO Cox regression analysis for establishing a risk score (RS) model. Kaplan–Meier approach indicated the high-risk group exhibited a shorter survival. Furthermore, we analyzed the tumor metastasis, age, and RS model status were determined to be independent clinical prognostic factors using Cox regression analysis. Decision curve analysis (DCA) indicated that the prognostic factor + RS model had the best net benefit. Finally, nine tumor-infiltrating immune cells (TIICs) showed significant differences in abundance between high- and low-risk groups via CIBERSORT deconvolution algorithm. In conclusion, the immune-related eleven-RNA signature be could served as a potential prognostic biomarker for osteosarcoma metastasis.

The Potential Adverse Impact of Post-Treatment Thrombocytopenia on Clinical Outcomes in Cancer Patients Treated With Immune Checkpoint Inhibitors.

The main goal of this study is to explore the prognostic and predictive implications of post-treatment thrombocytopenia on treatment efficacy and clinical outcomes in advanced-stage cancer treated with immune checkpoint inhibitors (ICIs). This retrospective study included 102 patients with advanced-stage cancer who were treated with ICIs. The simultaneous administration of chemotherapy and ICIs was omitted; nevertheless, the selection of chemotherapy agents employed in different treatment lines was left to the discretion of the attending clinician. Patients were stratified into distinct cohorts based on their post-treatment platelet counts (evaluated for up to four to six months after the completion of ICI). The primary endpoint of interest was progression-free survival (PFS), and overall survival (OS) was the secondary endpoint. Patients with superior Eastern Cooperative Oncology Group (ECOG) performance status and those who received ICI as second-line treatment displayed markedly elevated incidences of grade 1 thrombocytopenia (p < 0.05). Kaplan-Meier survival analysis confirmed that patients with high-grade thrombocytopenia had significantly shorter PFS (six vs. 13 vs. 19 months, p < 0.0001) and OS (10 vs. 21 vs. 25 months, p < 0.0001) than those with lower grades or without thrombocytopenia, respectively. Multivariate analysis revealed that decreased platelet levels were a negative independent prognostic factor for both PFS and OS in patients with advanced-stage cancer who received ICIs. The results of this retrospective study suggest that a decline in platelet levels after treatment represents a dependable adverse prognostic biomarker for clinical outcomes. Moreover, a decrease in platelet levels has been linked to reduced treatment efficacy in advanced-stage cancer patients receiving ICIs, thereby providing valuable prognostic insights for the implementation of personalized treatment strategies in cancer immunotherapy.

Induction versus Adjuvant Chemotherapy Combined with Concurrent Chemoradiation: What Is Beneficial in Locally Advanced Nasopharyngeal Carcinoma—A 5-Year Comparative Study at a Tertiary Care Center in North India

Background In locally advanced nasopharyngeal cancer (LANPC), concurrent chemoradiotherapy (CCRT) has been established as the current standard of care, but recently, the addition of induction chemotherapy to CCRT has presented an attractive multidisciplinary approach. Objectives The aim of the study was to explore the clinical outcome of induction chemotherapy (IC) followed by CCRT and CCRT followed by adjuvant chemotherapy (AC) in LANPC. Material and Methods In this propensity score–matched retrospective cohort study, we enrolled LANPC patients from October 2016 to June 2022. Study variables were evenly distributed by propensity score matching. Independent prognostic factors were identified using Cox regression analysis, and the outcome between the two chemotherapy treatment combinations was compared for patients in different subgroups. Result A total of 80 patients were included in the study. Survival outcomes indicated that the IC followed by CCRT group (IC + CCRT) achieved a higher 5-year overall survival (OS; 90 vs. 81%, p = 0.253), failure-free survival (FFS; 80 vs. 77.50%, p = 0.17), and distant metastasis-free survival (DMFS; 88 vs. 82.50%, p = 0.314) compared with the CCRT followed by AC group (CCRT + AC), although it was not statistically significant. The stratified analysis revealed that IC followed by CCRT (IC + CCRT) was associated with significantly improved OS (hazard ratio [HR] = 0.212; 95% confidence interval [CI] = 0.014–3.16; p = 0.0026) in N2 disease. However, the superiority of CCRT followed by AC (CCRT + AC) was only observed in LRRFS (HR = 0.45; 95% CI = 0.05–0.89; p = 0.036) for the T4 subgroup. Conclusion In patients with LANPC, especially with T3 or N2 disease, IC should be strongly considered followed by CCRT.

SFTPB in serum extracellular vesicles as a biomarker of progressive pulmonary fibrosis.

Progressive pulmonary fibrosis (PPF), defined as the worsening of various interstitial lung diseases (ILDs), currently lacks useful biomarkers. To identify novel biomarkers for early detection of patients at risk of PPF, we performed a proteomic analysis of serum extracellular vesicles (EVs). Notably, the identified candidate biomarkers were enriched for lung-derived proteins participating in fibrosis-related pathways. Among them, pulmonary surfactant-associated protein B (SFTPB) in serum EVs could predict ILD progression better than the known biomarkers, serum KL-6 and SP-D, and it was identified as an independent prognostic factor from ILD-gender-age-physiology index. Subsequently, the utility of SFTPB for predicting ILD progression was evaluated further in 2 cohorts using serum EVs and serum, respectively, suggesting that SFTPB in serum EVs but not in serum was helpful. Among SFTPB forms, pro-SFTPB levels were increased in both serum EVs and lungs of patients with PPF compared with those of the control. Consistently, in a mouse model, the levels of pro-SFTPB, primarily originating from alveolar epithelial type 2 cells, were increased similarly in serum EVs and lungs, reflecting pro-fibrotic changes in the lungs, as supported by single-cell RNA sequencing. SFTPB, especially its pro-form, in serum EVs could serve as a biomarker for predicting ILD progression.

The Expression of Forkhead Box P3 T Regulatory Lymphocytes as a Prognostic Factor in Malignant Melanomas.

Since transcription factor Forkhead Box P3 (FoxP3) was identified as a specific regulatory T cell (Treg) marker, researchers have scrutinized its value as a potential novel therapeutic target or a prognostic factor in various types of cancer with inconsistent results. The present analysis was performed to assess the influence of Treg FoxP3 expression on the prognosis of primary melanoma and to evaluate the correlations with various clinicopathological prognostic factors. We analyzed all eligible patients with stage pT3 primary malignant melanomas treated in a tertiary cancer center. Immunohistochemical staining for Treg FoxP3 expression was performed on retrospectively identified paraffin blocks and subsequently correlated with the outcomes of the patients. A total of 81% of the patients presented a positive Treg FoxP3 expression, being correlated with a higher risk of lymph node metastasis, tumor relapse, and death. Moreover, positive expression was statistically associated with a shorter OS. The tumor relapse rate was estimated at 36.7%. A positive expression of Treg FoxP3 and lymph node metastasis were associated with a higher risk of death based on multivariate analysis. Treg FoxP3 expression may be used as an independent prognostic factor in patients with malignant melanoma to evaluate tumor progression and survival.

TMX2 potentiates cell viability of hepatocellular carcinoma by promoting autophagy and mitophagy

ABSTRACT The dysregulation of membrane protein expression has been implicated in tumorigenesis and progression, including hepatocellular carcinoma (HCC). In this study, we aimed to identify membrane proteins that modulate HCC viability. To achieve this, we performed a CRISPR activation screen targeting human genes encoding membrane-associated proteins, revealing TMX2 as a potential driver of HCC cell viability. Gain- and loss-of-function experiments demonstrated that TMX2 promoted growth and tumorigenesis of HCC. Clinically, TMX2 was an independent prognostic factor for HCC patients. It was significantly upregulated in HCC tissues and associated with poor prognosis of HCC patients. Mechanistically, TMX2 was demonstrated to promote macroautophagy/autophagy by facilitating KPNB1 nuclear export and TFEB nuclear import. In addition, TMX2 interacted with VDAC2 and VADC3, assisting in the recruitment of PRKN to defective mitochondria to promote cytoprotective mitophagy during oxidative stress. Most interestingly, HCC cells responded to oxidative stress by upregulating TMX2 expression and cell autophagy. Knockdown of TMX2 enhanced the anti-tumor effect of lenvatinib. In conclusion, our findings emphasize the pivotal role of TMX2 in driving the HCC cell viability by promoting both autophagy and mitophagy. These results suggest that TMX2 May serve as a prognostic marker and promising therapeutic target for HCC treatment. Abbreviation: CCCP: Carbonyl cyanide 3-chlorophenylhydrazone; Co-IP: co-immunoprecipitation; CRISPR: clustered regularly interspaced short palindromic repeat; ER: endoplasmic reticulum; HCC: hepatocellular carcinoma; KPNB1: karyopherin subunit beta 1; PRKN: parkin RBR E3 ubiquitin protein ligase; ROS: reactive oxygen species; TFEB: transcription factor EB; TMX2: thioredoxin related transmembrane protein 2; VDAC2: voltage dependent anion channel 2; VDAC3: voltage dependent anion channel 3; WB: western blot.