Independent Predictive Marker Research Articles

Handgrip strength as a predictor of 1‑year mortality after hip fracture surgery in the Colombian Andes Mountains.

The aim of this study was to determine the association between low HGS and 1-year mortality in a cohort of older patients over 60years old with fragility hip fractures who underwent surgery in the Colombian Andes Mountains. A total of 126 patients (median age 81years, women 77%) with a fragility hip fracture during 2019-2020 were admitted to a tertiary care hospital. HGS was measured using dynamometry upon admission, and data about sociodemographic, clinical and functional, laboratory, and surgical intervention variables were collected. They were followed up until discharge. Those who survived were contacted by telephone at one, three, and 12months. Bivariate, multivariate, and Kaplan-Meier analyses with survival curves were performed. The prevalence of low HGS in the cohort was 71.4%, and these patients were older, had poorer functional and cognitive status, higher comorbidity, higher surgical risk, time from admission to surgery > 72h, lower hemoglobin and albumin values, and greater intra-hospital mortality at one and three months (all p < 0.01). Mortality at one year in in patients with low HGS was 42.2% and 8.3% in those with normal HGS, with a statistically significant difference (p = 0.000). In the multivariate analysis, low HGS and dependent gait measured by Functional Ambulation Classification (FAC) were the factors affecting postoperative 1-year mortality in older adults with hip fractures. In this study of older people with fragility hip fractures, low HGS and dependent gait were independent predictive markers of 1-year mortality.

Clinical Characteristics and Treatment Outcomes of Thyroid Cancer at a Tertiary Care Hospital in Najran Region, Saudi Arabia: A Single-Centre Retrospective Study.

Background The global incidence of thyroid cancer has increased significantly over the past decades. This study aims to review the clinical characteristics and treatment outcomes of thyroid cancer at the Tertiary Care Hospital in the Najran region of Saudi Arabia. Material and methods We conducted a retrospective study of 279 patients diagnosed with thyroid cancer at our hospital from March 2014 to December 2021. Clinicopathologic parameters were obtained from the patient's medical records and examined using univariate and multivariate Cox regression to identify independent predictive markers. Result The mean age was 42.8 ±14.5 years, and most cases were female (n= 203, 72.8%).Most cases (n=170, 60.9%) underwent total thyroidectomy. Additionally, lymph node dissection was performed in 28 (10.0%) cases.Localized disease, distant, and regional metastasis were observed in 214 (76.7%), 34 (12.2%), and 31 (11.1%), respectively. The neck lymph nodes and lungs were the most common metastasis regions in 19 (6.8%) and 11 (3.9%) cases, respectively.Papillary thyroid cancer and follicular thyroid cancers accounted for the majority of cases in 236 (84.6%) and 33 (11.8%), respectively. Adjuvant therapy, including radioactive iodine ablation, was reported in 51 (18.3%) and external beam radiotherapy in four (1.4%). Independent prognostic factors of overall mortality of thyroid carcinoma were older age (Hazard ratio (HR):1.05, 95% confidence interval (CI): 1.01-1.09, p=0.008), Diabetic mellitus (HR: 4.30, 95% CI: 1.11-16.62, p=0.035), pathologic subtype of follicular carcinoma (HR: 4.48, 95% CI: 1.07-18.73, p=0.040) or non-papillary thyroid carcinoma subtypes (HR: 12.56, 95% CI: 2.44-64.74, p=0.002), metastasis presentation (HR: 11.70, 95% CI: 3.30-41.46, p<0.001), pulmonary metastasis (HR: 27.92, 95% CI: 6.96-111.98, p<0.001), bone and liver metastasis (HR: 15.20, 95% CI: 1.70-135.98, p=0.015), tumor size >4 cm (HR:121.21, 95% CI: 15.33-958.34,p<0.001), and extrathyroidal extension (HR: 6.15, 95% CI: 1.59-23.77, p=0.009). Conclusion This study demonstrates that advanced age, the presence of diabetes, non-papillary thyroid carcinoma subtypes, metastatic disease, tumor size greater than 4 cm, and extrathyroidal extension are independently associated with a poorer prognosis in patients with thyroid carcinoma. To offer the finest modern care, a multidisciplinary approach should be employed when developing a tailored treatment strategy, considering relevant recommendations and stratification systems.

The relative and combined ability of triglyceride-glucose index and stress hyperglycemia ratio to predict major adverse cardio-cerebral events in patients with multivessel coronary artery disease

BackgroundCardiovascular disease continues to be the leading cause of global mortality and disability, particularly posing elevated risks in patients diagnosed with multivessel disease (MVD). Efficient risk stratification in MVD patients is crucial for improving prognosis, prompting investigation into novel biomarkers such as the triglyceride-glucose index (TyG index) and the stress hyperglycemia ratio (SHR).MethodsThis study enrolled a cohort comprising 679 patients diagnosed with MVD who underwent coronary angiography at Tianjin Chest Hospital. Patients were stratified into four groups based on their TyG index levels, categorized as TyG index-L and TyG index-H, and SHR levels, categorized as SHR-L and SHR-H. The primary endpoint was the occurrence of major adverse cardio-cerebral events (MACCEs). This Study conducted univariate and multivariable Cox regression analyses to assess the association between TyG index and SHR levels, both as continuous and categorical variables, in relation to MACCEs. Kaplan–Meier survival curves were employed to evaluate the correlation among patient groups.ResultsDuring a mean follow-up of 61 months, 153 cases of MACCEs were recorded. The TyG index and SHR served as independent predictors of long-term prognosis in patients with MVD, whether considered as continuous or categorical variables. Multivariable analysis revealed that patients with TyG index-H + SHR-H group exhibited the highest incidence of MACCEs (HR: 2.227; 95% CI 1.295–3.831; P = 0.004). The area under the curve (AUC) for predicting MACCEs was 0.655 for TyG index, 0.647 for SHR, and 0.674 when combined.ConclusionThis study underscores the potential of the TyG index and SHR as independent and combined predictive markers for MACCEs in patients with MVD. Their integrated assessment enhances risk stratification, providing valuable insights for personalized treatment strategies aimed at optimizing patient prognosis.

Mcl-1 expression is a predictive marker of response to gemcitabine plus nab-paclitaxel for metastatic pancreatic cancer

Antiapoptotic protein, including Mcl-1, expression is frequently observed in pancreatic cancer. Gemcitabine plus nabpaclitaxel (GnP) is the standard chemotherapy for metastatic pancreatic cancer (MPC); however, predictive markers for its efficacy remain unestablished. This study evaluated the association between GnP’s therapeutic effects and Mcl-1 expression in tissue samples obtained using endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for pancreatic tumor or percutaneous ultrasound-guided biopsy for metastatic liver tumor. We retrospectively reviewed 38 patients with histologically diagnosed MPC who received GnP as the first-line chemotherapy at our institute between December 2014 and July 2018. Post-immunohistochemistry analysis for Mcl-1 expression detection, patients were divided to into two groups based on the cell proportion showing Mcl-1 immunoreactivity: positive (> 20%; 23 [60.5%] patients) and negative (≤ 20%; 15 [39.5%] patients) groups. Clinical characteristics did not differ between the two groups. The Mcl-1 positive group showed a significantly higher disease control rate (95.7% vs. 73.3%; P = 0.046), longer progressionfree survival (PFS) (7.2 months vs. 4.9 months; P = 0.018) and longer overall survival (OS) (14.9 months vs. 9.2 months; P = 0.008) than the Mcl-1 negative group. Multivariate analysis showed that Mcl-1 expression was an independent predictive marker for PFS and OS. Mcl-1 expression could be a predictive marker for favorable response to GnP.

Development and validation of a nomogram to predict overall survival in patients with glioma: a population-based study.

The objective is to investigate the prognostic factors associated with gliomas and to develop and assess a predictive nomogram model connected to survival that may serve as an additional resource for the clinical management of glioma patients. From 2010 to 2015, participants included in the study were chosen from the Surveillance Epidemiology and End Results (SEER) database. Gliomas were definitively diagnosed in each of them. They were divided into the training group and the validation cohort at random (7/3 ratio) using a random number table. To identify the independent predictive markers for overall survival (OS), Cox regression analysis was utilized. Subsequently, the training cohort's survival-related nomogram predictive model for OS was created by incorporating the fundamental patient attributes. Following that, the training cohort's model underwent internal validation. The nomogram model's authenticity and reliability were assessed through the computation of receiver operating characteristic (ROC) curves and concordance index (C-index). To evaluate the degree of agreement between the observed and predicted values in the training and validation cohorts, calibration plots were created. Age, primary site, histological type, surgery, chemotherapy, marital status, and grade were the independent predictive factors for OS in the training cohort, according to Cox regression analysis. Moreover, the nomogram model for predicting 1-year, 3-year, and 5-year OS was built using these variables. The C-indexes of OS for glioma patients in the training cohort and internal validation cohort were found to be 0.779 (95% CI=0.769-0.789) and 0.776 (95% CI=0.760-0.792), respectively, according to the results. The ROC curves also demonstrated good discrimination. Additionally, calibration plots demonstrated a fair amount of agreement. In summary, the nomogram prediction model of OS demonstrated a moderate level of reliability in its predictive performance, offering valuable reference data to enable doctors to quickly and easily determine the survival likelihood of patients with gliomas.

Abstract 6277: Tall cell variant papillary thyroid carcinoma from Middle Eastern patients have worse outcome than classical papillary thyroid carcinoma using propensity score matching

Abstract The tall cell variant of Papillary Thyroid Carcinoma (TCV-PTC) is the most common aggressive variant of PTC. The impact of TCV-PTC on patients’ prognosis still remains controversial. Moreover, the clinico-pathological and prognostic effect of TCV-PTC from Middle Eastern ethnicity remains unexplored. We aimed to study TCV-PTC in comparison to classical PTC in Middle Eastern patients and their impact on prognosis. We performed a retrospective cohort study of tall cell variant (TCV-PTC) and classic variant of papillary thyroid carcinoma (CV-PTC) after post-surgical radioactive iodine therapy. We used the propensity score matching (1:3 matching ratio) to account for differences between recipients of TCV-PTC vs CV-PTC. Univariate and multivariate analysis were performed to assess the independent factors for persistent/recurrent disease. Kaplan-Meier curve analyses were used to compare disease-free survival (DFS). In total, 174 (16.3%) patients with TCV-PTC and 891 (83.7%) patients with CV-PTC were included. After propensity score matching, 174 pairs of patients were selected (TCV-PTC, n = 174; CV-PTC, n = 522). In the matched analysis, higher proportions of TCV-PTC experienced persistent/recurrent disease compared with CV-PTC (25.7% vs 31.4%; p = 0.0119). In multivariate analyses of clinical and tumor characteristics, histological type of TCV-PTC (odds ratio, 2.09; 95% confidence interval, 1.28-3.40; p = 0.0031) was associated with increased risk of persistent/recurrent disease. The five-year DFS rates for the TCV-PTC and CV-PTC groups were 48.5% and 73.1%, respectively. The Kaplan- Meier analysis indicated that the TCV-PTC group (p &amp;lt; 0.0001) had shorter DFS. In conclusion, when other clinico-pathological factors were similar, this propensity score matched analysis showed that histological subtype TCV-PTC is by itself an independent predictive marker of persistent/recurrent disease in Middle Eastern patients. Therefore, individualized therapeutic approaches might be needed for this aggressive PTC subtype. Citation Format: Khawla S. Al-Kuraya, Sandeep K. Parvathareddy, Abdul K. Siraj, Saeeda O. Ahmed, Nabil Siraj, Manal Manakhan, Hassan Aldossari. Tall cell variant papillary thyroid carcinoma from Middle Eastern patients have worse outcome than classical papillary thyroid carcinoma using propensity score matching [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6277.

Predictive and prognostic value of excision repair cross-complementing group 1 in patients with advanced gastric cancer

BackgroundTo define the optimal chemotherapy regimen for each patient we therefore used tissue from patients to identify molecular prognostic or predictive biomarkers.MethodsEndoscopic biopsy specimens from primary lesions and surgical specimens on a phase III trial in patients with unresectable advanced or recurrent gastric cancer treated with docetaxel with cisplatin plus S-1 (DCS) or cisplatin plus S-1 (CS), were collected. We measured the mRNA expression of ERCC1 and analyzed SNPs in GSTP1 and ERCC1.ResultsLow ERCC1 expression was associated with favorable prognosis for overall survival, OS by multivariable analysis (P = 0.001). There were significant interactions between the two treatment arms of DCS and CS, and ERCC1 mRNA expression. In patients with low ERCC1 expression of a favorable prognosis, DCS therapy was inferior to CS (P = 0.046). In addition to GSTP1 rs1695 (HR 1.728), ERCC1 rs3212980, ERCC1 rs2298881, ERCC1 rs3212964 with high expression of ERCC1 mRNA were associated with significantly worse prognosis with regard to OS.ConclusionsERCC1 mRNA is an independent prognostic factor and predictive marker that can be used to guide the addition of docetaxel. The SNPs of ERCC1 and GSTP1 could be also prognostic or predictive factors.

Visceral Adipose Tissue Percentage Compared to Body Mass Index as Better Indicator of Surgical Outcomes in Women With Obesity and Endometrial Cancer

Study ObjectiveTo assess the impact visceral adipose tissue percentage (VAT%) on surgical outcomes during minimally invasive surgery in obese women with endometrial cancer. DesignRetrospective observational cohort study. SettingMie University Hospital, Japan. PatientsOf the 73 women (body mass index [BMI] >30 kg/m2) with obesity and primary endometrial cancer, 52 underwent robotic surgery, while 21 underwent laparoscopic surgery between April 2014 and December 2022. InterventionsWe investigated the correlation between surgical outcomes (operative time and blood loss) and obesity (BMI and visceral adipose tissue percentage [VAT%]). Measurements and Main ResultsAbdominal fat-related parameters were measured at the level of the umbilicus using preoperative computed tomography. A weak negative correlation was found between BMI and VAT% (CC = −0.313, p = .001). Multivariate analysis showed that VAT% had a stronger correlation to total and practical operative time than BMI (β = 0.338 vs 0.267, β = 0.311 vs 0.209, respectively) and was an independent predictor of blood loss. VAT% was an independent predictive marker prolonged for operative time and increased blood loss during lymphadenectomy. ConclusionVAT% could be an indicator of surgical outcomes for patients with obesity and endometrial cancer.

Long-Term Impact of Various Endocrine Therapy Regimens on Mortality, Local Recurrence, and Metastasis in Breast Cancer: A 25-Year Retrospective Study

Background: This retrospective cohort study explores the long-term effects of different endocrine therapy regimens on mortality, local recurrence, and metastasis in breast cancer patients. Methods: Data from the Referral Cancer Research Center of Shahid Beheshti University of Medical Sciences were analyzed. Records of 2,262 histologically confirmed breast cancer patients, with 25 years of follow-up were included. We collected patient data, including treatment modalities, and details of the endocrine therapy, and conducted statistical analysis to assess treatment-outcome associations. Results: Patients had an average age of 49.45 years, and 99.1% were female. The average tumor size was 2.8 cm, with a 12.3% mortality rate. Positive expression of human epidermal growth factor receptor 2, progesterone receptor, and estrogen receptor was found in 17.3%, 71.8%, and 70.6% of patients, respectively. Tamoxifen was administered to 1,700 patients, letrozole to 715, and exemestane to 540, with an average endocrine therapy duration of 5.2 years. Letrozole treatment duration (P = 0.001) and lymph node involvement (P = 0.028) were independent predictive variables for local recurrence, with longer letrozole therapy associated with lower recurrence. Conclusion: Estrogen receptor expression and endocrine therapy duration are independent predictive markers for recurrence and mortality. Longer letrozole therapy predicts lower local recurrence. Endocrine therapy duration inversely relates to mortality, recurrence, and local recurrence.

The neutrophil percentage-to-albumin ratio is an independent risk factor for poor prognosis in peritoneal dialysis patients

Aim This study aimed to investigate the predictive ability of the neutrophil percentage-to-albumin Ratio (NPAR) concerning all-cause mortality and cardio-cerebrovascular mortality in patients undergoing peritoneal dialysis (PD). Methods We included a total of 807 PD patients from the Peritoneal Dialysis Center of the Second Affiliated Hospital of Soochow University between January 2009 and December 2019 in this study. Patients were categorized into three groups based on their baseline NPAR. The Kaplan-Meier method, multivariate Cox proportional hazard model, and Fine-Gray competing risk model were employed to examine the relationship between NPAR level and all-cause mortality and cardio-cerebrovascular mortality among PD patients. Furthermore, the ROC curve and calibration plots were utilized to compare the performance between NPAR and other conventional indicators. Results The mean follow-up period was 38.2 months. A total of 243 (30.1%) patients passed away, with 128 (52.7%) succumbing to cardio-cerebrovascular diseases. The mortality rates of the Middle and High NPAR groups were significantly greater than that of the Low NPAR group (p < 0.001), and NPAR was independently associated with all-cause mortality and cardio-cerebrovascular mortality. Receiver Operating Characteristic (ROC) analysis indicated that the Area Under the Curve (AUC) of NPAR (0.714) was significantly superior to those of C-reactive protein (CRP) (0.597), neutrophil to lymphocyte ratio (NLR) (0.589), C-reactive protein to albumin ratio (CAR) (0.698) and platelet to lymphocyte ratio (PLR) (0.533). Conclusion NPAR served as an independent predictive marker for all-cause mortality and cardio-cerebrovascular mortality in PD patients. Moreover, NPAR demonstrated superior predictive potential compared to CRP, CAR, NLR, and PLR.

Platelet-to-lymphocyte ratio as a prognostic predictive marker on adults with traumatic brain injury: Systematic review.

The platelet-to-lymphocyte ratio (PLR) has emerged as a prognostic predictive marker in various diseases, but its role in traumatic brain injury (TBI) has not been fully elucidated. This study aims to evaluate the role of PLR as a prognostic predictive marker in adults with TBI. This systematic review was conducted according to the Preferred Reporting Items in the Systematic Review and Meta-analysis Guidelines 2020. A comprehensive search was performed using PubMed, Google Scholar, Scopus, Crossref, OpenAlex, Semantic Scholar, Library of Congress, and Jisc Library Hub Discover database to identify relevant studies published up to February 2023. Both prospective and retrospective observational studies written in English or Indonesian were included in the study. No restrictions were placed on the year and country of publication and duration of follow-up. Study quality was evaluated using the Newcastle-Ottawa Scale (NOS), and the risk of bias was estimated using the Cochrane Risk of Bias Assessment Tool for Nonrandomized Research (Ro-BANS) tool. A narrative synthesis was also conducted to summarize the findings. We retrieved 1644 references using the search strategy, and 1623 references were excluded based on screening the title and abstract. The full text was retrieved for 20 articles and subjected to the eligibility criteria, of which 16 were excluded from the study. Four papers with a total of 1.467 sample sizes were included in the review. The median of NOS for study quality was 8-9, with the risk of selection bias using the Ro-BANS tool being low in all studies except for the blinding outcome assessments, which are all unclear. The study finding suggests that the PLR has the potential as an independent prognostic predictive marker in adult patients with TBI. In three studies, a high level of admission PLR may independently predict an increasing mortality risk in 30 days and adverse outcomes measured by the Glasgow outcome scale in 6 months following TBI. However, one study shows that PLR may have limited value as a predictor of mortality or favorable neurological outcomes compared to other hematological parameters. Further studies were needed to establish the clinical utility of PLR and fill the present gaps. This systematic review provides evidence supporting the utilization of PLR as a prognostic predictive marker in adult patients with TBI. The PLR can mainly be utilized, especially in rural practice, as PLR is a simple, low-cost, and routinely performed hematological examination.

Elevated Risk of Adverse Prognosis in Patients with T2-3 Stage Breast Cancer Exhibiting Non-Pathological Complete Response Following Neoadjuvant Chemotherapy: Significance of Regenerating Islet-Derived Family Member 4.

In this study, we aimed to establish the role of regenerating islet-derived family member 4 (Reg IV) as an independent risk factor and prognostic predictor in patients with T2-3 stage breast cancer who exhibit a non-pathological complete response (non-pCR) following neoadjuvant chemotherapy (NACT). Additionally, we examined the potential correlation and interaction between Reg IV and epidermal growth factor receptor (EGFR). A total of 67 patients with T2-3 stage breast cancer exhibiting non-pCR after NACT between September 2019 and December 2021 were included in this study. The analysis involved Kaplan-Meier survival comparisons, pooled hazard ratios for risk quantification, Cox regression analysis to isolate the impact of Reg IV on prognosis, Riskplots for visualizing risk profiles, and SHAP analysis to assess the importance of variables in predicting outcomes. The findings indicate that patients positive for Reg IV had a significantly poorer prognosis (HR: 2.62, 95% CI: 1.06-6.47). Co-expression of Reg IV and EGFR was associated with the worst outcomes compared to patients negative for both markers. Cox regression analysis confirmed the independent prognostic impact of Reg IV (HR: 2.63, 95% CI: 1.66-3.59). Riskplot analysis showed that patients positive for both Reg IV and EGFR predominantly experienced disease progression. SHAP analysis further reinforced the significant effect of Reg IV on the disease course, without substantial interaction with EGFR. Reg IV may serve as an independent risk factor and predictive marker for adverse outcomes in patients with T2-3 stage breast cancer who do not achieve non-pCR following NACT.

The importance of biglycan, decorin and TGF-1 levels in the diagnosis of non-small cell lung cancer

BACKGROUND: Despite Non-small cell lung cancer (NSCLC) ranks among the most deadly cancers worldwide, and currently, apart from a low percentage, targetable molecules have not been identified in its etiopathogenesis. The relationship between the proteoglycans decorin and biglycan, which are present in the extracellular matrix of cells, and transforming growth factor Beta-1 (TGF-B1), has been shown in many cancers. We investigated the significance of these molecules in NSCLC. METHODS: Fasting serum levels of decorin, biglycan, and TGF-B1 were obtained from 48 newly diagnosed NSCLC patients and compared with those of 48 adult control subjects matched for age and demographics. Demographic data, baseline laboratory values, and ELISA results were compared between the groups. RESULTS: The median age was 65(39–83) similar in both groups. There was no relation between demographic and clinical parameters and the levels of decorin, biglycan, and TGF-B1 in the NSCLC group. However, in comparison to the control group, NSCLC patients had significantly higher levels of biglycan (42.55 ± 27.40 vs. 24.38 ± 12.05 ng/mL, p= 0.026) and TGF-B1 (15.55 ± 9.16 vs. 10.07 ± 7.8 pg/mL, p= 0.001), while decorin levels were significantly lower (6.64 ± 1.92 vs. 10.28 ± 3.13 ng/mL, p= 0.002). In the multivariate regression analysis; Decorin &lt; 8.13 ng/mL (OR, 10.96; 95% CI: 3.440–34.958), current smoking (OR, 3.81; 95% CI: 1.320–10.998), COPD (OR, 43.6; 95% CI: 2.082–913.081), and lower BMI (OR, 1.22; 95% CI: 1.070–1.405, p= 0.003) were identified as independent predictive markers for NSCLC diagnosis. CONCLUSION: The decreased serum decorin level is an independent marker for NSCLC. Further studies are needed to investigate the prognostic significance of decorin on survival and its potential as a target in treatment.

Variation in presepsin and thrombomodulin levels for predicting COVID-19 mortality

Coronavirus disease (COVID-19) has caused extensive mortality globally; therefore, biomarkers predicting the severity and prognosis of COVID-19 are essential. This study aimed to evaluate the application of presepsin (P-SEP) and thrombomodulin (TM), which are biomarkers of sepsis and endothelial dysfunction, respectively, in the prognosis of COVID-19. Serum P-SEP and TM levels from COVID-19 patients (n = 183) were measured. Disease severity was classified as mild, moderate I, moderate II, or severe based on hemoglobin oxygen saturation and the history of intensive care unit transfer or use of ventilation at admission. Patients in the severe group were further divided into survivors and non-survivors. P-SEP and TM levels were significantly higher in the severe group than those in the mild group, even after adjusting for creatinine values. In addition, TM levels were significantly higher in non-survivors than in survivors. Changes in the P-SEP levels at two time points with an interval of 4.1 ± 2.2 days were significantly different between the survivors and non-survivors. In conclusion, TM and continuous P-SEP measurements may be useful for predicting mortality in patients with COVID-19. Moreover, our data indicate that P-SEP and TM values after creatinine adjustment could be independent predictive markers, apart from renal function.

Transferrin receptor 1 promotes hepatocellular carcinoma progression and metastasis by activating the mTOR signaling pathway.

Aberrant iron metabolism is commonly observed in multiple tumor types, including hepatocellular carcinoma (HCC). However, as the key regulator of iron metabolism involved in iron absorption, the role of transferrin receptor (TFRC) in HCC remains elusive. The mRNA and protein expression of TFRC were evaluated in paired HCC and adjacent non-tumor specimens. The correlation between TFRC level and clinicopathological features or prognostic significance was also analyzed. The role of TFRC on biological functions was finally studied in vitro and in vivo. The TFRC level was remarkably upregulated in HCC tissues compared to paired peritumor tissues. Overexpressed TFRC positively correlated with serum alpha-fetoprotein, carcinoembryonic antigen, and poor tumor differentiation. Multivariate analysis demonstrated that upregulated TFRC was an independent predictive marker for poorer overall survival and disease-free survival in HCC patients. Loss of TFRC markedly impaired cell proliferation and migration in vitro and notably suppressed HCC growth and metastasis in vivo, while overexpression of TFRC performed an opposite effect. Mechanistically, the mTOR signaling pathway was downregulated with TFRC knockdown, and the mTOR agonist MHY1485 completely reversed the biological inhibition in HCC cells caused by TFRC knockdown. Furthermore, exogenous ferric citrate (FAC) or iron chelator reversed the changed biological functions and signaling pathway expression of HCC cells caused by TFRC knockdown or overexpression, respectively. Our study indicates that TFRC exerts an oncogenic role in HCC and may become a promising therapeutic target to restrain HCC progression.

High density of CXCL12-positive immune cell infiltration predicts chemosensitivity and recurrence-free survival in ovarian carcinoma

BackgroundOvarian carcinoma is the most lethal gynecologic malignancy because of its late diagnosis, extremely high recurrence rate, and limited curative treatment options. In clinical practice, high-grade serous carcinoma (HGSC) predominates due to its frequency, high aggressiveness, and rapid development of drug resistance. Recent evidence suggests that CXCL12 is an important immunological factor in ovarian cancer progression. Therefore, we investigated the predictive and prognostic significance of the expression of this chemokine in tumor and immune cells in patients with HGSC.MethodsWe studied a cohort of 47 primary high-grade serous ovarian carcinomas and their associated recurrences. A tissue microarray was constructed to evaluate the CXCL12 immunostained tumor tissue. CXCL12 expression was evaluated and statistically analyzed to correlate clinicopathologic data, overall survival, and recurrence-free survival.ResultsA high proportion of CXCL12 + positive immune cells in primary ovarian serous carcinoma correlated significantly with chemosensitivity (p = 0.005), overall survival (p = 0.021), and longer recurrence-free survival (p = 0.038). In recurrent disease, high expression of CXCL12 was also correlated with better overall survival (p = 0.040). Univariate and multivariate analysis revealed that high CXCL12 + tumor-infiltrating immune cells (TICs) (HR 0.99, p = 0.042, HR 0.99, p = 0.023, respectively) and combined CXCL12 + /CD66b + infiltration (HR 0.15, p = 0.001, HR 0.13, p = 0.001, respectively) are independent favorable predictive markers for recurrence-free survival.ConclusionA high density of CXCL12 + TICs predicts a good response to chemotherapy, leading to a better overall survival and a longer recurrence-free interval. Moreover, with concomitant high CXCL12/CD66b TIC density, it is an independent favorable predictor of recurrence-free survival in patients with ovarian carcinoma.

Baseline neutrophil-lymphocyte ratio and platelet-lymphocyte ratio appear predictive of immune treatment related toxicity in hepatocellular carcinoma.

A well-recognized class effect of immune checkpoint inhibitors (ICI) is immune-related adverse events (IrAEs) ranging from low grade toxicities to life-threatening end organ damage requiring permanent discontinuation of ICI. Deaths are reported in < 5% of patients treated with ICI. There are, however, no reliable markers to predict the onset and severity of IrAEs. We tested the association between neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) at baseline with development of clinically significant IrAEs (grade ≥ 2) in hepatocellular carcinoma (HCC) patients treated with ICI. To test the association between NLR and PLR at baseline with development of clinically significant IrAEs (grade ≥ 2) in HCC patients treated with ICI. Data was extracted from an international database from a consortium of 11 tertiary-care referral centers. NLR = absolute neutrophil count/absolute lymphocyte count (ALC) and PLR = platelet count/ALC. Cutoff of 5 was used for NLR and 300 for PLR based on literature. We also tested the association between antibiotic and steroid exposure to IrAEs. Data was collected from 361 patients treated between 2016-2020 across the United States (67%), Asia (14%) and Europe (19%). Most patients received Nivolumab (n = 255, 71%). One hundred sixty-seven (46%) patients developed at least one IrAE, highest grade 1 in 80 (48%), grade ≥ 2 in 87 (52%) patients. In a univariable regression model PLR > 300 was significantly associated with a lower incidence of grade ≥ 2 IrAEs (OR = 0.40; P = 0.044). Similarly, a trend was observed between NLR > 5 and lower incidence of grade ≥ 2 IrAEs (OR = 0.58; P = 0.097). Multivariate analyses confirmed PLR > 300 as an independent predictive marker of grade ≥ 2 IrAEs (OR = 0.26; P = 0.011), in addition to treatment with programmed cell death ligand 1 (PD-1)/cytotoxic T lymphocyte-associated protein-4 (OR = 2.57; P = 0.037) and PD-1/tyrosine kinase inhibitor (OR = 3.39; P = 0.01) combinations. Antibiotic use was not associated with IrAE incidence (OR = 1.02; P = 0.954). Patients treated with steroids had a > 2-fold higher incidence of grade ≥ 2 IrAEs (OR = 2.74; P < 0.001), although 74% were prescribed steroids for the treatment of IrAEs. Given that high baseline NLR and PLR are associated with a decreased incidence of IrAEs, lower baseline NLR and PLR may be predictive biomarkers for the appearance of IrAEs in HCC treated with ICI. This finding is in keeping with several studies in solid tumors that have shown that baseline NLR and PLR appear predictive of IrAEs.

Radiomics Model for Predicting FOXP3 Expression Level and Survival in Clear Cell Renal Carcinoma

We aimed to evaluate the predictive significance of forkhead box protein 3 (FOXP3) expression levels among individuals with clear cell renal carcinoma (ccRCC) and establish a radiomics model for predicting FOXP3 expression. 430 patients with ccRCC were included in the gene-based prognostic analyses; 100 samples were used for radiomics feature generation, model development, and evaluation. A gradient boosting machine was employed to model the selected radiomics features. The developed model generated radiomics scores (RS) that predicted FOXP3 expression. The FOXP3 prognostic model combining imaging features was applied for survival and clinical indicator correlation analyses. FOXP3 was highly expressed in patients with ccRCC and served as an independent predictive marker (hazard ratio [HR]=2.357, 95% CI [confidence interval]: 1.582-3.511, p<0.001). The radiomics model formed by three radiomics characteristics was identified as a strong prognostic indicator of overall survival (OS). The predictive power of the model was commendable (areas under the curve: 0.835 and 0.809 for training and validation sets, respectively). Significant between-group variations in RS distribution were identified, as indicated by gene expression levels (p<0.05). Disparities were observed in pathological stage, pharmaceutical therapy, and neoplasm status between low and high RS cohorts (p<0.001). Kaplan-Meier curves revealed a significant correlation between increased RS and decreased OS (p=0.001), which was also observed in the multivariate analyses (HR=3.411, 95% CI: 1.039-11.196, p=0.043). Prognostic outcome of ccRCC is closely linked to FOXP3 expression level. Computed tomography-based radiomics shows promise for prognostic prediction in ccRCC.

Interaction between intratumoral microbiota and tumor mediates the response of neoadjuvant therapy for rectal cancer.

Previous observations have demonstrated that the response to neoadjuvant chemoradiotherapy (nCRT) is highly variable in patients with locally advanced rectal cancer (LARC). Recent studies focusing on the intratumoral microbiota of colorectal cancer have revealed its role in oncogenesis and tumor progression. However, limited research has focused on the influence of intratumoral microbiota on the nCRT of LARC. We explored the microbial profiles in the tumor microenvironment of LARC using RNA-seq data from a published European cohort. Microbial signatures were characterized in pathological complete response (pCR) and non-pCR groups. Multi-omics analysis was performed between intratumor microbiomes and transcriptomes. Microbial α and β diversity were significantly different in pCR and non-pCR groups. Twelve differential microbes were discovered between the pCR and non-pCR groups, six of which were related to subclusters of cancer-associated fibroblasts (CAFs) associated with extracellular matrix formation. A microbial risk score based on the relative abundance of seven differential microbes had predictive value for the nCRT response (AUC = 0.820, p < 0.001). Our study presents intratumoral microbes as potential independent predictive markers for the response of nCRT to LARC and demonstrates the underlying mechanism by which the interaction between intratumoral microbes and CAFs mediates the response to nCRT.

Is it possible to predict Surgical Site Infection?

Surgical site infection (SSI) is a widely seen postoperative complication that causes a decrease in life quality and an economic burden. In this study, we aim to find the predictive values of preoperative and postoperative neutrophile lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) values for SSI. In this retrospective study, 698 patients who had total abdominal hysterectomy operations with benign indications and confirmed histopathological results were accessed. In this study, the correlation of preoperative NLR, preoperative PLR, postoperative NLR, and postoperative PLR, with the occurrence of postoperative surgical site infection complications were examined. The overall SSI rate was 9.46% (n = 66) with 30 days follow-up postoperatively. Preoperative NLR and PLR values of the patients who had SSIs were significantly lower than the control group (p < 0.05). Postoperative NLR and PLR values of the patients who had SSIs were significantly higher than control group (p < 0.05). In the patients who had postoperative SSIs, the increase of the values of postoperative NLR and PLR were significantly higher than the control group (p < 0.05). In our study, hematological markers of NLR and PLR were found to be independent and significant predictive markers for SSI.