The Predictive Efficacy of Serum Exosomal microRNA-122 and microRNA-148a for Hepatocellular Carcinoma Based on Smart Healthcare

Objective. Hepatocellular carcinoma (HCC) remains a devastating tumor globally. Serum exosomes are reliable biomarkers for tumors, including HCC. Hence, this study explored the efficacy and mechanism of serum exosomes in HCC. Methods. microRNA (miR)-122 and miR-148a expressions in serum exosomes from HCC patients and healthy subjects and their predictive efficacy for HCC were detected. Correlation between serum exosomal miR-122/148a expressions with survival rate, clinical stage, lymph node metastasis, and tumor differentiation level and levels of HCC-related serum markers (CA199, FucAFP, ALD-A, and AFu) were detected. PAX2 staining intensity and expression in HCC were measured. PAX2 predictive efficacy for HCC and its correlation with clinical stage, lymph node metastasis, tumor differentiation level, and HCC-related serum marker levels were analyzed. The targeted binding relationship between miR-122 and miR-148a and PAX2 was predicted and verified. Results. Serum exosomal miR-122 and miR-148a expressions were downregulated in HCC, showing potent predictive efficacy for HCC, which was negatively related to clinical stage and lymph node metastasis and positively related to tumor differentiation level, patient survival rate, and HCC-related serum marker levels. PAX2 showed increased staining intensity and expression in HCC, together with high predictive efficacy for HCC. PAX2 expression showed a positive correlation with clinical stage and lymph node metastasis and a negative correlation with tumor differentiation level and HCC-related serum marker levels. miR-122 and miR-148a conjointly targeted PAX2 in HCC. Conclusion. We demonstrated that serum exosomal miR-122 and miR-148a played a predictive role and were linked to prognosis in HCC via interactions with PAX2.

Oncogenic NRAS Accelerates Rhabdomyosarcoma Formation When Occurring within a Specific Time Frame during Tumor Development in Mice

In the Ptch+/- mouse model for embryonal rhabdomyosarcoma (ERMS), we recently showed that oncogenic (onc) H-, K- or NRAS mutations do not influence tumor growth when induced at the advanced, full-blown tumor stage. However, when induced at the invisible ERMS precursor stage at 4 weeks of age, tumor development was enforced upon oncHRAS and oncKRAS but not by oncNRAS, which instead initiated tumor differentiation. These data indicate that oncRAS-associated processes differ from each other in dependency on the isoform and their occurrence during tumor development. Here, we investigated the outcome of oncNRAS induction at an earlier ERMS precursor stage at 2 weeks of age. In this setting, oncNRAS accelerates tumor growth because it significantly shortens the ERMS-free survival and increases the ERMS incidence. However, it does not seem to alter the differentiation of the tumors. It is also not involved in tumor initiation. Together, these data show that oncNRAS mutations can accelerate tumor growth when targeting immature ERMS precursors within a specific time window, in which the precursors are permissive to the mutation and show that oncNRAS-associated processes differ from each other in dependency on their occurrence during tumor development.

A combined prediction model for biliary tract cancer using the prognostic nutritional index and pathological findings: a single-center retrospective study

Background The prognostic nutritional index, a marker of nutritional status and systemic inflammation, is a known biomarker for various cancers. However, few studies have evaluated the predictive value of the prognostic nutritional index in patients with biliary tract cancer. Therefore, we investigated the prognostic significance of the prognostic nutritional index, and developed a risk-stratification system to identify prognostic factors in patients with biliary tract cancer. Methods Between July 2010 and March 2021, 117 patients with biliary tract cancer were recruited to this single-center, retrospective study. The relationship between clinicopathological variables, including the prognostic nutritional index, and overall survival was analyzed using univariate and multivariate analyses. A P < 0.05 was considered statistically significant. Results The median age was 75 (range 38–92) years. Thirty patients had intrahepatic cholangiocarcinoma; 29, gallbladder carcinoma; 27, distal cholangiocarcinoma; 17, ampullary carcinoma; and 13, perihilar cholangiocarcinoma. Curative (R0) resection was achieved in 99 patients. In univariate analysis, the prognostic nutritional index (< 42), lymph node metastasis, carbohydrate antigen 19-9 level (> 20 U/mL), preoperative cholangitis, tumor differentiation, operation time (≥ 360 min), and R1–2 resection were significant risk factors for overall survival. The prognostic nutritional index (P = 0.027), lymph node metastasis (P = 0.040), and tumor differentiation (P = 0.006) were independent prognostic factors in multivariate analysis. A combined score of the prognostic nutritional index and pathological findings outperformed each marker alone, in terms of discriminatory power. Conclusions The prognostic nutritional index, lymph node metastasis, and tumor differentiation were independent prognostic factors after surgical resection in patients with biliary tract cancer. A combined prediction model using the prognostic nutritional index and pathological findings accurately predicted prognosis, and can be used as a novel prognostic factor in patients with biliary tract cancer.

Prognostic Nomogram for Liver Metastatic Colon Cancer Based on Histological Type, Tumor Differentiation, and Tumor Deposit: A TRIPOD Compliant Large-Scale Survival Study

ObjectiveA proportional hazard model was applied to develop a large-scale prognostic model and nomogram incorporating clinicopathological characteristics, histological type, tumor differentiation grade, and tumor deposit count to provide clinicians and patients diagnosed with colon cancer liver metastases (CLM) a more comprehensive and practical outcome measure.MethodsUsing the Transparent Reporting of multivariable prediction models for individual Prognosis or Diagnosis (TRIPOD) guidelines, this study identified 14,697 patients diagnosed with CLM from 1975 to 2017 in the Surveillance, Epidemiology, and End Results (SEER) 21 registry database. Patients were divided into a modeling group (n=9800), an internal validation group (n=4897) using computerized randomization. An independent external validation cohort (n=60) was obtained. Univariable and multivariate Cox analyses were performed to identify prognostic predictors for overall survival (OS). Subsequently, the nomogram was constructed, and the verification was undertaken by receiver operating curves (AUC) and calibration curves.ResultsHistological type, tumor differentiation grade, and tumor deposit count were independent prognostic predictors for CLM. The nomogram consisted of age, sex, primary site, T category, N category, metastasis of bone, brain or lung, surgery, and chemotherapy. The model achieved excellent prediction power on both internal (mean AUC=0.811) and external validation (mean AUC=0.727), respectively, which were significantly higher than the American Joint Committee on Cancer (AJCC) TNM system.ConclusionThis study proposes a prognostic nomogram for predicting 1- and 2-year survival based on histopathological and population-based data of CLM patients developed using TRIPOD guidelines. Compared with the TNM stage, our nomogram has better consistency and calibration for predicting the OS of CLM patients.

Preoperative Tumor Abnormal Protein as a Promising Biomarker to Predict Oncological Outcome of Hepatocellular Carcinoma After Curative Resection

Background: TAP (tumor abnormal protein) has been used as an important indicator in the early diagnosis of cancers, and some literatures showed that TAP can act as a prognostic factor in different kinds of cancer. The objective of this study was to explore the potential relationship between TAP and the prognosis of HCC after radical hepatectomy, and attempted to construct a robustly predictive nomogram on the strength of TAP and other prognostic variables of HCC patients.Methods: This retrospective study included 168 HCC patients (tumor recurrence occurred in 78 patients) who had undergone curative resection during January 2018 to June 2020 at the Department of Hepatopancreatobiliary Surgery of Liaoning Cancer Hospital & Institute. Serum TAP was detected by Abnormal Sugar Chain Structure of Glycoproteins, and according to the area of condensation particle, the whole population was categorized into the TAP high group (TAP≥225μm2) and TAP low group (TAP<225μm2).Results: There was no correlation between maximum tumor size and TAP. In the whole population or subgroups stratified by maximum tumor size, the recurrence-free survival (RFS) rate of the TAP low group was distinctly higher than TAP high group (P<0.05 for all). The multivariate analysis revealed that TAP (hazard ratio [HR], 3.47; 95% CI, 2.18-5.51; P<0.001), large tumor size (HR, 2.18; 95% CI, 1.36-3.49; P<0.001), poor tumor differentiation (HR, 0.53; 95% CI, 0.33-0.84; P=0.007) and presence of microvascular invasion (MVI) (HR, 2.03; 95% CI, 1.28-3.22; P=0.003) were independently associated with RFS. The prognostic implication of nomogram incorporating TAP, maximun tumor diameter, tumor differentiation and MVI was stronger than the model that integrated maximun tumor diameter, degree of tumor differentiation and MVI only.Conclusion: The present study suggested that higher preoperative TAP was correlated with undesirable prognosis in HCC patients who had undergone radical hepatectomy,and on the strength of prognostic variables identified by multivariate analysis, we constructed a robust nomogram for RFS of postoperative HCC patients.

The Clinical And Prognostic Value of NLR, PDW, And PNI In Advanced Non-Small-Cell Lung Cancer Treated With Platinum-Based Chemotherapy

Objective: The purpose of this study was to investigate the relationship between the neutrophil-lymphocyte ratio (NLR), platelet distribution width (PDW) and prognostic nutrient index (PNI), and the prognosis of patients with advanced non-small-cell lung cancer (NSCLC) treated with platinum-based chemotherapy.Methods: A total of 428 patients with advanced NSCLC treated with platinum-based chemotherapy between January 2015 and June 2019 were retrospectively analyzed. The patients were randomly divided into training set (n=300) and test set (n=128) in a ratio of 7:3, respectively. Clinical data and peripheral blood test results were collected within one week prior to the initiation of treatment to calculate PDW, NLR, and PNI. Receiver operating characteristic (ROC) curves were used to determine the optimal cut-off values of PLR, PDW, and PNI. Kaplan-Meier method and Cox regression analysis were used to evaluate the prognostic factors of advanced NSCLC treated with platinum-based chemotherapy. A Nomogram model was established for predicting the prognosis in advanced NSCLC treated with platinum-based chemotherapy. The test set was used for external validation of the prognostic model.Results: There was no significant difference in the proportion of clinical features between the training set and the test set (P＞0.05). The ROC curve analysis determined the optimal cut-off values of PLR, PDW, and PNI to be 3.07, 16.81, and 52.025, respectively. Univariate and multivariate analyses indicated that tumor type (P=0.038), tumor differentiation (P=0.014), NLR (P=0.001), PDW (P<0.001), and PNI (P=0.009) were independent prognostic factors for PFS in patients with advanced NSCLC patients treated with platinum-based chemotherapy. Tumor type (P=0.002), tumor differentiation (P=0.038), EGFR status (P=0.002), NLR (P=0.010), PDW (P=0.001), and PNI (P=0.002) were independent prognostic factors for overall survival (OS) in advanced NSCLC patients treated with platinum-based chemotherapy. The established nomogram was validated internally and externally. The results showed a good agreement between the predicted value and the actual value of the calibration curve.Conclusion: NLR, PDW, PNI, tumor type, and tumor differentiation are independent prognostic factors for PFS in advanced NSCLC patients treated with platinum-based chemotherapy. NLR, PDW, PNI, tumor type, tumor differentiation, and EGFR status are independent prognostic factors for OS in advanced NSCLC patients treated with platinum-based chemotherapy. The established model has an application value in predicting the prognosis of advanced NSCLC patients treated with platinum-based chemotherapy.

The Prognostic Impact of Tumor Differentiation on Recurrence and Survival after Resection of Hepatocellular Carcinoma Is Dependent on Tumor Size

<b><i>Introduction:</i></b> The present study aimed to evaluate the effect of poor differentiation and tumor size on survival outcome after hepatic resection of hepatocellular carcinoma (HCC). <b><i>Methods:</i></b> A total of 1,107 patients who underwent initial and curative hepatic resection for HCC without macroscopic vascular invasion participated in the study. Using the multivariable Cox proportional hazards regression model, we evaluated changes in hazard ratios (HRs) for the association between tumor differentiation and survival based on tumor size. <b><i>Results:</i></b> In patients with poorly (Por) differentiated HCCs, the adjusted HRs of reduced overall survival (OS), recurrence-free survival (RFS), early RFS, and early extrahepatic RFS were 1.31 (95% confidence interval [CI]; 1.07–1.59), 1.07 (95% CI 0.89–1.28), 1.31 (95% CI 1.06–1.62), and 1.81 (95% CI 1.03–3.17), respectively. Moreover, based on an analysis of the effect modification of tumor differentiation according to tumor size, Por HCC was found to be associated with a reduced OS (<i>p</i> = 0.033). The HRs of Por HCCs sharply increased in patients with tumors measuring up to 5 cm. The adjusted HRs of reduced OS in patients with Por HCCs measuring &#x3c;2, ≥2 and &#x3c;5, and ≥5 cm were 1.22 (95% CI 0.69–2.14), 1.33 (95% CI 1.02–1.73), and 1.58 (95% CI 1.04–2.42), respectively. The corresponding adjusted HRs of reduced early RFS were 0.85 (95% CI 0.46–1.57), 1.34 (95% CI 1.01–1.8), and 1.57 (95% CI 1.03–2.39), respectively. The adjusted HRs of reduced early extrahepatic RFS were 1.89 (95% CI 0.83–4.3) in patients with tumors measuring ≥2 and &#x3c;5 cm and 2.33 (95% CI 0.98–5.54) in those with tumors measuring ≥5 cm. <b><i>Conclusions:</i></b> Por HCC measuring ≥2 cm was associated with early recurrence. Hence, it had negative effects on OS. After surgery, patients with Por HCC measuring ≥5 cm should be cautiously monitored for early extrahepatic recurrence. These findings will help physicians devise treatment strategies for patients with HCC.

The Benefit of Apparent Diffusion Coefficient in Evaluating the Invasiveness of Hepatocellular Carcinoma

BackgroundThis study aimed to evaluate hepatocellular carcinoma (HCC) invasiveness using the apparent diffusion coefficient (ADC).MethodsEighty-one patients with HCC confirmed by pathology and examined by preoperative magnetic resonance imaging diffusion-weighted imaging from January 2015 to September 2020 were retrospectively analyzed. Clinical and pathological data were recorded. The minimum ADC (ADCmin), average ADC (ADCmean), and the ratio of ADCmean to normal-appearing hepatic parenchyma ADC (ADCnahp) were assessed. The associations between clinical information, ADC value, and HCC invasiveness (microvascular invasion [MVI], tumor differentiation, and Ki-67 expression) were evaluated statistically. Independent risk factors related to HCC invasiveness were screened using binary logistic regression, and the diagnostic efficiency was evaluated by the receiver operating characteristic curve and its area under the curve (AUC) value.ResultsTumor size was related to HCC MVI and tumor differentiation (P &lt; 0.05). HCC MVI was associated with ADCmin, ADCmean, and the ADCmean-to-ADCnahp ratio (all P &lt; 0.05) with AUC values of 0.860, 0.860, and 0.909, respectively. If these were combined with tumor size, the AUC value increased to 0.912. The degree of tumor differentiation was associated with ADCmin, ADCmean, and the ADCmean-to-ADCnahp ratio (all P &lt; 0.05) with AUC values of 0.719, 0.708, and 0.797, respectively. If these were combined with tumor size, the AUC value increased to 0.868. Ki-67 expression was associated with ADCmin, ADCmean, and the ADCmean-to-ADCnahp ratio (all P &lt; 0.05) with AUC values of 0.731, 0.747, and 0.746, respectively. Combined them, the AUC value increased to 0.763.ConclusionsThe findings indicated that the ADC value has significant potential for the non-invasive preoperative evaluation of HCC invasiveness.