Independent Risk Factor For Disease-free Survival Research Articles

Inflammatory myofibroblastic tumor in the head and neck—a neoplasm with both tumor features and inflammation

The aim of this study was to unveil the reciprocal relation of tumor characteristics and inflammation in inflammatory myofibroblastic tumor in the head and neck. The study included a retrospective cohort of patients with inflammatory myofibroblastic tumors treated between 2005 and 2017 in a tertiary hospital. Tumor features and inflammation were assessed through the expression of anaplastic lymphoma kinase (ALK), the degree of inflammation and cyclooxygenase-2 (COX-2) expression. The prognostic factors were analyzed for overall survival (OS) and disease-free survival (DFS) in univariate and multivariate analyses. Forty-one patients diagnosed with inflammatory myofibroblastic tumors were followed up, and 41 paraffin sections were obtained. The positive rate of ALK expression was 21 (51.2%) of 41 patients. Nineteen patients had high-grade ALK expression, and 22 patients had low-grade ALK expression. Thirty-nine patients had high-grade inflammation, and 2 had low-grade inflammation. The positive rate of COX-2 expression was 100%. Tumors with both high-grade ALK expression and inflammation had worse DFS (P=.015). The multivariate Cox analysis showed that the grades of ALK expression and inflammation (P=.004) were independent risk factors for DFS. Because of the latent synergistic effects of ALK and inflammation in the tumorigenesis of inflammatory myofibroblastic tumor, the combined therapy of ALK and COX-2 inhibitors shows promise.

INHBA is a prognostic predictor for patients with colon adenocarcinoma

BackgroundColon adenocarcinoma (COAD) is one of the most lethal cancers. It is particularly important to accurately predict prognosis and to provide individualized treatment. Several lines of evidence suggest that genetic factors and clinicopathological characteristics are related to cancer onset and progression. The aim of this study was to identify potential prognostic genes and to develop a nomogram to predict survival and recurrence of COAD.MethodsTo identify potential prognostic genes in COAD, microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were obtained from GEO2R. Venn diagram was drawn to select those genes that were overexpressed in all datasets, and survival analyses were performed to determine the prognostic values of the selected genes. New nomograms were developed based on the genes that were significantly associated with prognosis. Clinicopathological data were obtained from The Cancer Genome Atlas (TCGA). Finally, the new nomograms were compared head-to-head comparison with the TNM nomogram.ResultsFrom GSE21510, GSE110223, GSE113513 and GSE110224, a total of 834, 218, 236 and 613 overexpressed DEGs were screened out, respectively. The Venn diagram revealed that 12 genes appeared in all four profiles. After survival analyses, only INHBA expression was associated with both overall survival (OS) and disease-free survival (DFS). Multivariate analyses revealed that age, pathological N and pathological M were significant independent risk factors for OS. Age, pathological N, pathological M and INHBA were significant independent risk factors for DFS. Two prediction models predicted the probability of 3-year survival and 5-year survival for OS and DFS, respectively. The concordance indexes were 0.785 for 3-year overall survival, 0.759 for 5-year overall survival, 0.789 for 3-year disease-free survival and 0.757 for 5-year disease-free survival. The head-to-head comparison according to time-dependent ROC curves indicated that the new models had higher predictive accuracy. Decision curve analyses (DCA) indicated that the clinical value of the new models were higher than TNM models for predicting disease-free survival.ConclusionThe combination of INHBA expression with a clinical nomogram improves prognostic power in colon adenocarcinoma, especially for predicting recurrence.

Clinical Significance of Preoperative Serum Carcinoembryonic Antigen Within the Normal Range in Colorectal Cancer Patients Undergoing Curative Resection.

Serum carcinoembryonic antigen (CEA) is a widely used tumor marker in colorectal cancer (CRC), but within normal range of preoperative CEA levels the clinical significance of CEA is unknown. The aim of this study was to evaluate the usefulness of CEA within the normal range as a prognosticator of non-metastatic CRC. This retrospective cohort study included 2021 CRC patients with normal preoperative CEA who underwent elective curative surgery (discovery group). We determined the optimal cut-off value for disease-free survival (DFS) discrimination using the Contal and O'Quigley method. We also assessed the prognostic significance of the cut-off value in a prospective cohort of 171 stage III colon cancer patients treated with oxaliplatin-based adjuvant chemotherapy (validation group). The optimal cut-off CEA value was 2.1ng/mL in the discovery group. The DFS rates were significantly poorer in patients with high-normal preoperative CEA levels (2.1-5.0ng/mL) than in those with low-normal CEA levels (< 2.1ng/mL) in both groups. A high-normal CEA level was an independent risk factor for DFS in both groups, and was associated with inferior DFS in patients with stage II and III disease and in never or former smokers. The correlation between DFS and CEA levels was more distinct in left-sided colon and rectal cancer. A high-normal preoperative CEA level (≥ 2.1ng/mL), even within the normal range, was an independent prognosticator for poor DFS in CRC. The usefulness of CEA was influenced by smoking status and tumor location in addition to tumor stage.

Mucinous Adenocarcinoma as a High-risk Factor in Stage II Colorectal Cancer: A Propensity Score-matched Study from Japan.

The purpose of this study was to investigate the clinical, pathological, and prognostic differences between adenocarcinoma (ADC) and mucinous adenocarcinoma (MUC) in colorectal cancer (CRC). This was a retrospective study of a Japanese high-volume cancer Center over a 10-year period. From April 2007 to December 2016, a total of 3,296 patients with primary CRC were included in the study. The clinical characteristics of MUC and ADC were compared. Then, propensity score matching was performed according to a 1:2 ratio. Multivariate analysis was used for independent risk factors related to prognosis. The overall survival (OS) and disease-free survival (DFS) of 126 cases of MUC and 256 cases of ADC were studied, as well as the survival rate of each stage. MUC accounts for 3.82% of the total CRC. Compared to ADC, MUC is more common in female patients (47.62% vs. 38.77%; p=0.045), with higher carcinoembryonic antigen levels (56.35% vs. 34.95%; p<0.001), more ulcerative and infiltrative types (82.54% vs. 72.93%; p=0.016), higher incidence of perineural infiltration (51.59% vs. 41.04%; p=0.018), deeper infiltration (T3-T4: 90.48% vs. 65.84%; p<0.001), and more advanced cancer (stage III-IV: 59.52% vs. 44.79%; p=0.001). MUC is also more likely to recur (24.6% vs. 14.32%; p=0.001). Regarding the long-term survival rate, the OS (p<0.001) and DFS (p=0.05) is consequently worse. After propensity score matching, multivariate analysis showed that MUC was a common independent risk factor for DFS [odds ratio (OR)=4.277; 95% confidence interval (CI), 0.327-0.97; p=0.039], and also for OS (OR= 6.836; 95% CI, 0.274-0.831; p=0.009). In MUC, OS and DFS were still relatively worse (OS: p=0.017; DFS: p=0.038). However, only significant statistical differences were shown in stage II (OS: p=0.003; DFS: p=0.007). No significant differences were noted in the stages I, III, or IV. MUC is a high-risk factor for stage II CRC. Adjuvant chemotherapy should be routinely recommended for patients with MUC stage II, and special attention should be paid during their follow-up.

Neoadjuvant chemotherapy-induced decrease of prognostic nutrition index predicts poor prognosis in patients with breast cancer

BackgroundThe prognostic nutritional index (PNI), which is an easily calculated nutritional index, is significantly associated with patient outcomes in various solid malignancies. This study aimed to evaluate the prognostic impact of PNI changes in patients with breast cancer undergoing neoadjuvant chemotherapy (NAC).MethodsWe reviewed patients with breast cancer who underwent NAC and a subsequent surgery for breast cancer between 2005 and 2016. PNI before and after NAC were calculated using the following formula: 10 × serum albumin (g/dl) + 0.005 × total lymphocyte count/mm3. The relationship between PNI and prognosis was retrospectively analyzed.ResultsIn total, 191 patients were evaluated. There was no significant difference in disease-free survival (DFS) between the pre-NAC PNI high group and the pre-NAC PNI low group (cutoff: 53.1). However, PNI decreased in 181 patients (94.7%) after NAC and the mean PNI also significantly decreased after NAC from 52.6 ± 3.8 pre-NAC to 46.5 ± 4.4 post-NAC (p < 0.01). The mean ΔPNI, which was calculated as pre-NAC PNI minus post-NAC PNI, was 5.4. The high ΔPNI group showed significantly poorer DFS than the low ΔPNI group (cut off: 5.26) (p = 0.015). Moreover, high ΔPNI was an independent risk factor of DFS on multivariate analysis (p = 0.042).ConclusionsHigh decrease of PNI during NAC predicts poor prognosis. Thus, maintaining the nutritional status during NAC may result in better treatment outcomes in patients with breast cancer.

Patient-derived xenograft model engraftment predicts poor prognosis after surgery in patients with pancreatic cancer

ObjectivesTo establish and evaluate a first generation patient-derived xenograft (PDX) model in nude mice using tumors resected from pancreatic cancer (PC) patients for the identification of key factors that influence xenograft success and prediction of patient prognosis. MethodsPrimary tumor samples harvested from PC patients who underwent curative resection between May 2016 and April 2018 at our hospital were xenografted into nude mice. Tumor size was evaluated for 2 months. Patients’ baseline characteristics and follow-up data were analyzed. ResultsTumor xenograft models were generated from 67 patients; 30 (44.8%) were successful and 37 (55.2%) failed. Xenograft models could recapitulate the pathology and genetic information of the primary tumors. Univariate analysis identified tumor engraftment, post-operation CA19-9, tumor size, lymph node status, and lymphovascular invasion as significant predictors (P=0.000, 0.023, 0.004, 0.035 and 0.005, respectively) of disease-free survival (DFS). Multivariate Cox regression analysis confirmed tumor engraftment, tumor size and lymphovascular invasion function as independent risk factors for DFS (P=0.000, 0.039 and 0.025, respectively). The hazard ratio of tumor engraftment for DFS was 0.239 (95% confidence interval, 0.109 to 0.524). Kaplan–Meier analysis of DFS indicated an unfavorable outcome in the engraftment group compared to that in the failed engraftment group (6.2 vs. 12.2 months, log rank P=0.000). ConclusionThe pathology and genetic information of primary PC tumors are recapitulated in the PDX tumor model in nude mice. Furthermore, engraftment success is an effective predictor of disease recurrence in patients after surgery.

Cancer-derived immunoglobulin G: A novel marker for differential diagnosis and relapse prediction in parathyroid carcinoma.

A differential diagnosis between malignant and benign parathyroid lesions is difficult due to their overlapping clinicopathological characteristics. As such, molecular markers are urgently needed. Cancer-derived immunoglobulin G (CIgG) is a novel molecule playing important roles in carcinogenesis. The present study aimed to investigate the clinical significance of CIgG in parathyroid neoplasms. Fifty patients with parathyroid carcinoma (PC), 50 patients with parathyroid adenoma (PA) and 9 patients with parathyroid hyperplasia (PH) were retrospectively enrolled in the current study. Immunohistochemistry was used to assess CIgG expression in these patients. The performance of CIgG expression in the differential diagnosis between parathyroid lesions was assessed by receiver operating characteristic (ROC) curves. The associations between CIgG expression and clinical outcomes were also analysed by Kaplan-Meier survival curves and Cox proportional hazards models. The expression level of CIgG was significantly higher in PC patients than in PA or PH patients (P<.001). CIgG expression discriminated PC from PA or PH, with an area under the ROC curve of 0.84 (76% sensitivity and 88% specificity). High CIgG expression was significantly associated with worse disease-free survival (DFS) in PC patients (P=.018) and was validated as an independent risk factor for DFS in the multivariable Cox regression analysis (P=.002). The ability of CIgG expression both in the differential diagnosis between malignant and benign parathyroid lesions and in the prognosis prediction for PC was shown in the present study. CIgG might be used as a novel biomarker of parathyroid lesions in future clinical practice.

Prognostic impact of acellular mucin pools towards the patients with locally advanced rectal cancer achieving pathological complete response after preoperative chemoradiotherapy.

Background:To date, the prognostic significance of acellular mucin pools in tumors from patients with locally advanced rectal cancer (LARC) undergoing preoperative chemoradiotherapy (CRT) and subsequently obtaining pathological complete response (pCR) has not been well determined. Our current study aimed to explore the prognostic impact on these patients of acellular mucin pools.Methods:We collected clinical data from 117 consecutive LARC patients who achieved pCR after preoperative CRT and then underwent radical resection. Two groups of patients were generated, according to the presence or absence of acellular mucin pools. The 5-year disease-free survival (DFS) and overall survival (OS) rates were compared between the two groups of patients.Results:A total of 27 (23.1%) patients presented with acellular mucin pools. At a median follow-up period of 64 months, patients with acellular mucin pool showed a 5-year DFS rate (96.3% versus 83.7%, p = 0.110) and 5-year OS rate (100% versus 87.5%, p = 0.054) statistically similar to those of patients without acellular mucin pools. In univariable and multivariable Cox regression analyses, the presence of acellular mucin pools was not determined as an independent risk factor for DFS [hazard ratio (HR): 0.222; 95% confidence interval (CI): 0.029–1.864; p = 0.145] or OS (HR: 0.033; 95% CI: 0.000–9.620; p = 0.238).Conclusions:Acellular mucin pools had no significant prognostic impact on LARC patients showing pCR after preoperative CRT.

Cholecystectomy is associated with higher risk of recurrence after microwave ablation of hepatocellular carcinoma: a propensity score matching analysis.

Objective: To explore the association between cholecystectomy and the prognostic outcomes of patients with hepatocellular carcinoma (HCC) who underwent microwave ablation (MWA).Methods: Patients with HCC (n = 921) who underwent MWA were included and divided into cholecystectomy (n = 114) and non-cholecystectomy groups (n = 807). After propensity score matching (PSM) at a 1:2 ratio, overall survival (OS) and disease-free survival (DFS) rates were analyzed to compare prognostic outcomes between the cholecystectomy (n = 114) and non-cholecystectomy groups (n = 228). Univariate and multivariate Cox analyses were performed to assess potential risk factors for OS and DFS. Major complications were also compared between the groups.Results: After matching, no significant differences between groups were observed in baseline characteristics. The 1-, 3-, and 5-year OS rates were 96.5%, 82.1%, and 67.1% in the cholecystectomy group, and 97.4%, 85.2%, and 74.4% in the non-cholecystectomy group (P = 0.396); the 1-, 3-, and 5-year DFS rates were 58.4%, 34.5%, and 26.6% in the cholecystectomy group, and 73.6%, 44.7%, and 32.2% in the non-cholecystectomy group (P = 0.026), respectively. The intrahepatic distant recurrence rate in the cholecystectomy group was significantly higher than that in the non-cholecystectomy group (P = 0.026), and the local tumor recurrence and extrahepatic recurrence rates did not significantly differ between the groups (P = 0.609 and P = 0.879). Multivariate analysis revealed that cholecystectomy (HR = 1.364, 95% CI 1.023–1.819, P = 0.035), number of tumors (2 vs. 1: HR = 2.744, 95% CI 1.925–3.912, P < 0.001; 3 vs. 1: HR = 3.411, 95% CI 2.021–5.759, P < 0.001), and γ-GT levels (HR = 1.003, 95% CI 1.000–1.006, P < 0.024) were independent risk factors for DFS. The best γ-GT level cut-off value for predicting median DFS was 39.6 U/L (area under the curve = 0.600, P < 0.05). A positive correlation was observed between cholecystectomy and γ-GT level (r = 0.108, 95% CI −0.001–0.214, P = 0.047). Subgroup analysis showed that the DFS rates were significantly higher in the non-cholecystectomy group than the cholecystectomy group when γ-GT ≥39.6 U/L (P = 0.044). The 5-, 10-, 15-, 20-, and 25-year recurrence rates from the time of cholecystectomy were 2.63%, 21.93%, 42.11%, 58.77%, and 65.79%, respectively. A significant positive correlation was observed between cholecystectomy and the time from cholecystectomy to recurrence (r = 0.205, 95% CI 0.016–0.379, P = 0.029). There were no significant differences in complications between groups (P = 0.685).Conclusions: Patients with HCC who underwent cholecystectomy were more likely to develop intrahepatic distant recurrence after MWA, an outcome probably associated with increased γ-GT levels. Moreover, the recurrence rates increased with time.

Hepatocellular carcinoma in old age: are there any benefits of liver resection in old age?

PurposeElderly individuals have comorbidities that can adversely affect surgical outcomes. Some studies reported that elderly patients with hepatocellular carcinoma (HCC) have higher liver- and non-liver–related deaths. Therefore, palliative treatments are preferred in these patients. We compared surgical treatment outcomes between young and old age groups.MethodsIn total, 233 liver resections were performed in patients with HCC from March 2012 to December 2018. We retrospectively reviewed medical records. The old age group was defined as patients aged more than 70 years. We compared perioperative characteristics and surgical outcomes and analyzed the prognostic factors for disease-free survival (DFS) and overall survival (OS) rates.ResultsThe young and old age group included 184 and 49 patients, respectively. Preoperative characteristics were similar. Major liver resection rate was similar (young age group, 26.1% vs. old age group, 20.4%), but the operation time was a little bit shorter in old age group. Major postoperative complications were 23 (12.5%) and 9 (18.4%) in the young and old age group (P = 0.351). Median non-liver–related overall survival were 80 and 76 months (P = 0.889) and liver-related OS were 76 and 76 months (P = 0.514) in the young and old age groups, respectively. Age was not an independent risk factor for DFS and OS.ConclusionElderly patients showed similar non-liver- and liver-related OS rates as young patients after liver resection. Postoperative complications were also similar. If elderly patients are well selected, they can receive curative treatment and show good surgical outcomes.

Tumor-infiltrating lymphocyte-derived MLL2 independently predicts disease-free survival for patients with early-stage oral squamous cell carcinoma.

MLL2 (mixed-lineage leukemia 2) is recognized as an essential role in regulating histone 3 lysine 4 tri-methylation (H3K4me3) in mammalian cells. It is frequently mutated to promote developmental diseases and tumor initiation. However, the expression pattern of MLL2 and its clinical significance for patients with early-stage oral squamous cell carcinoma (OSCC) remain totally unknown. Eighty-five samples of primary early-stage OSCC were enrolled in this retrospective study, and immunohistochemistry (IHC) was performed to detect the spatial pattern of MLL2. The diagnostic and prognostic value of MLL2 were assessed. MLL2 was widely expressed in tumor cells (TCs), fibroblast-like cells (FLCs), and tumor-infiltrating lymphocytes (TILs), both in tumor center and invasive tumor front, and showed no distributive heterogeneity. Moreover, regardless of cell types and microlocalization, patients with high expressed MLL2 had increased depth invasion of tumor (DOI). Besides, upregulation of MLL2TC and MLL2TIL in tumor center were both associated with poor differentiation, but showed no correlation with tumor growth with comparable Ki-67 levels. Prognostic analysis indicated that early-stage OSCC patients with enhanced MLL2TIL in invasive tumor front were susceptible to occur postoperative metastasis and recurrence. Indeed, patients with higher expressed MLL2TIL showed shorter overall survival (OS) and disease-free survival (DFS), and MLL2TIL in invasive tumor front was an independent risk factor of DFS. TIL-derived MLL2 in invasive tumor front was an independent prognostic factor of DFS for early-stage OSCC patients.

Risk scoring model to predict recurrence in locally advanced breast cancer (LABC) treated with neoadjuvant chemotherapy (NACT).

98 Background: Complete response (CR) to NACT portends favorable long term outcomes in LABC. There is a need for a tool to risk categorise patients for recurrence risk (RR), so that intensification of treatment can be offered to women with high risk of recurrence. Methods: A prospectively maintained database of LABC (between January 2007 to December 2012), who received NACT followed by definitive surgery, radiotherapy and endocrine therapy in endocrine sensitive disease was retrospectively analyzed for clinico-pathological and treatment factors affecting disease free survival (DFS). A risk scoring model was developed on the basis of beta coefficients of identified independent risk factors for DFS. Results: The incidence of loco-regional relapse was 8% and that of distant metastases was 32% in a dataset of 206 patients at a median follow-up of 47 months (IQR 24-62 mo). The independent risk factors for recurrence were index T stage [HR 1.8 (0.9-3.6)], N stage [HR 1.7 (0.4 – 4.7)], grade [HR 1.8 (0.8-4.2)], age less than and more than 40 years [HR 1.6 (0.4-0.9)], pathologic CR [HR 4.3 (1.7- 10.7)], intrinsic subtype [HR 2.2 (1.3-3.7)], and type of surgery (BCS vs MRM) [HR 2.2 (1.3-3.6)]. The ROC of the model for the prediction of recurrence was 0.67 (95 % CI: 0.61-0.75). The results of this model were validated by dividing the population into 3 risk groups: low risk (score less than 12), intermediate risk group (score between 13-15), high risk group (score 16 or more). The chances of recurrence are 16% versus 34% versus 57% in low, intermediate and high risk group respectively. Presence of three risk factors implies low risk, five intermediate and more than five high risk. Conclusions: The risk scoring model developed by us predicts RR and can be used for selecting patients for treatment intensification in high risk category.

Value of computed tomography evaluation in pathologic classification and prognosis prediction of gastric neuroendocrine tumors.

The study aims to investigate the correlation of CT characteristics with pathological classifications and the prognostic value of CT features in patients with gastric neuroendocrine neoplasms (g-NENs). Ninety-one cases of pathologically diagnosed g-NENs, including 15 cases of well-differentiated neuroendocrine tumors (NETs) (G1 and G2) and 76 cases of poor-differentiated neuroendocrine carcinomas (NECs) (G3 and MANEC) were retrospectively studied. All cases were included in correlation analysis of CT characteristics with pathologic grades. Among them, 76 patients who had fulfilled follow-up data were included for overall survival (OS) and disease-free survival (DFS) analysis. CT characteristics that favor poor differentiation include tumor location (fundus and cardia), larger tumor size (>3.0 cm), infiltrative growth, unclear tumor margin, serosa involvement, ulceration and lymph node metastasis (P<0.05). Most variables had sensitivities >80% and specificities >60% to distinguish NECs from NETs. Through log-rank analysis, it was revealed that serosa involvement, cystic degeneration, necrosis, heterogeneous enhancement and lymph node metastasis led to worse DFS and OS for patients with g-NENs (P<0.05). COX regression analysis showed that serosa involvement and lymph node metastasis were independent risk factor for DFS and OS, respectively, despite of grading, staging and therapeutic choices (P<0.05). Moreover, high Ki-67 index (>55%) in G3 g-NENs is in correlation with serosa involvement and lymph node metastasis; accordingly, patients with higher Ki-67 index had worse 1-year DFS (61.7% vs. 92.3%; P<0.05). CT characteristics can be useful discriminators and prognostic factors for g-NENs and may help identify G3 g-NEC from G3 g-NEN by revealing its poor differentiation and high invasive potential.

Integrin-α7 expression positively correlates with CD44 and CD133 expressions, and its high expression associates with advanced tumor features as well as poor survivals in non-small cell lung cancer patients

Background: This study aimed to explore the correlation of integrin-α7 (ITGA7) with common cancer stem cell marker (CD44 and CD133) expressions, clinicopathological characteristics and survival profiles in non-small cell lung cancer (NSCLC) patients. Methods: Two hundred and seventy NSCLC patients who underwent resection were reviewed in this study and the expressions of ITGA7, CD44 and CD133 were detected using immunohistochemistry (IHC) assay in tumor tissue specimens. The clinical data (including age, gender, pathological grade, tumor size, lymph node metastasis (LYN), and TNM stage), survival data [including disease-free survival (DFS) and overall survival (OS)] were collected. Results: The numbers of NSCLC patients with ITGA7 high expression, CD44 high expression and CD133 high expression were 170 (63.0%), 241 (89.3%) and 37 (13.7%) respectively, and ITGA7 expression was positively associated with CD44 expression and CD133 expression. ITGA7 high expression was associated with higher pathological grade, larger tumor size, LYN and elevated TNM stage. However, there was no correlation of ITGA7 expression with age or gender. As for survival, patients with ITGA7 high expression presented reduced DFS and OS compared with those with ITGA7 low expression. In addition, multivariate Cox’s proportional hazards regression model analyses exhibited that ITGA7 high expression, higher pathological grade and LYN were independent risk factors for DFS and OS in NSCLC patients. Conclusions: ITGA7 expression positively correlates with CD44 and CD133 expressions, and its high expression associates with advanced tumor features as well as poor survivals in NSCLC.

Elevated Preoperative Serum CA125 Predicts Larger Tumor Diameter in Patients with Hepatocellular Carcinoma and Low AFP Levels.

Aim Little is known about the association between cancer antigen 125 (MUC16/CA125) concentrations and tumor diameter of patients with hepatocellular carcinoma (HCC) and low AFP levels. To fill this gap in our knowledge, we conducted a retrospective study of 427 patients with HCC with AFP ≤200 ng/mL who underwent R0 resection at our center. Methods The associations between CA125 concentrations and patients' clinicopathological characteristics were analyzed. Survival vs CA125 levels was also evaluated between patient groups with CA125 ≤30 U/mL or CA125 >30 U/mL. Independent risk factors of disease-free survival (DFS) and overall survival (OS) were analyzed with Cox hazard regression model. Results Elevated preoperative serum CA125 was significantly associated with maximal tumor diameter (MTD) >5 cm and female sex (P < 0.001 and P=0.044, respectively). The DFS and OS of patients with CA125 ≤30 U/mL (n = 392) were significantly higher compared with those with CA125 >30 U/mL (n = 35) (P=0.003 and P=0.001 respectively). Multivariate analysis revealed that MTD >5 cm was an independent risk factor of DFS (HR = 1.891, 95% CI: 1.379–2.592, P < 0.001) and OS (2.709, 1.848–3.972, P < 0.001). Conclusions In conclusion, elevated preoperative serum CA125 predicted larger tumor diameter and poor prognosis after patients with HCC with AFP ≤200 ng/mL underwent R0 resection, which may be explained by the elevation of the preoperative serum CA125 level significantly associated with MTD>5 cm.

Analysis of clinical features and related prognosis in chromophobe renal cell carcinoma

Objective To investigate the clinical features of chromophobe renal cell carcinoma (chRCC) and analyze the factors affecting its prognosis. Methods Retrospectively analyze the case data of 66 patients with chRCC admitted to Beijing Friendship Hospital, Capital Medical University from October 2003 to September 2018, including 32 males and 34 females; the average age was (53.9±13.9) years and the age range was 24-85 years. To analyze the clinical symptoms, whether have hypertension, diabetes, tumor characteristics (size, side, location), surgical methods, TNM staging and other clinical features of patients, with disease-free survival (DFS) as the study endpoint. The survival curve was drawed by the kaplan-Meier method. Survival analysis was performed using Log-rank test, and the clinical features of prognosis were analyzed by Cox regression models. Results Among the 66 patients, the mean diameter of the tumor was (5.4±3.5) cm, 17 cases were ≥7 cm, 49 cases were <7 cm; 48 cases were asymptomatic, and 18 cases were symptomatic; 45 cases in T1, 15 cases in T2, 6 cases in T3; 33 cases were underwent radical nephrectomy, 32 cases were underwent nephron sparing surgery, 1 case was under the therapy of watchful waiting. The median follow-up time was 61 months, and the DFS in 1, 5, and 10 years were 94.6%, 91.3%, and 82.2%, respectively. Log-rank results showed that the maximum diameter of the tumor was related to the T stage and the survival time of the patients (P<0.05). Cox multivariate analysis showed that T stage was an independent risk factor for DFS (HR=8.102, P=0.027). Conclusions ChRCC is a type of kidney cancer with a good prognosis. Tumor staging is more common in T1 and T2 phases, patients with higher DFS in 5 and 10 years, and T staging is an independent risk factor for DFS in patients. Key words: Kidney neoplasms; Disease characteristics; Prognosis; Survival analysis

Integrin-α7 expression positively correlates with CD44 and CD133 expressions, and its high expression associates with advanced tumor features as well as poor survivals in non-small cell lung cancer patients.

BackgroundThis study aimed to explore the correlation of integrin-α7 (ITGA7) with common cancer stem cell marker (CD44 and CD133) expressions, clinicopathological characteristics and survival profiles in non-small cell lung cancer (NSCLC) patients.MethodsTwo hundred and seventy NSCLC patients who underwent resection were reviewed in this study and the expressions of ITGA7, CD44 and CD133 were detected using immunohistochemistry (IHC) assay in tumor tissue specimens. The clinical data (including age, gender, pathological grade, tumor size, lymph node metastasis (LYN), and TNM stage), survival data [including disease-free survival (DFS) and overall survival (OS)] were collected.ResultsThe numbers of NSCLC patients with ITGA7 high expression, CD44 high expression and CD133 high expression were 170 (63.0%), 241 (89.3%) and 37 (13.7%) respectively, and ITGA7 expression was positively associated with CD44 expression and CD133 expression. ITGA7 high expression was associated with higher pathological grade, larger tumor size, LYN and elevated TNM stage. However, there was no correlation of ITGA7 expression with age or gender. As for survival, patients with ITGA7 high expression presented reduced DFS and OS compared with those with ITGA7 low expression. In addition, multivariate Cox’s proportional hazards regression model analyses exhibited that ITGA7 high expression, higher pathological grade and LYN were independent risk factors for DFS and OS in NSCLC patients.ConclusionsITGA7 expression positively correlates with CD44 and CD133 expressions, and its high expression associates with advanced tumor features as well as poor survivals in NSCLC.

HBV DNA levels impact the prognosis of hepatocellular carcinoma patients with microvascular invasion.

To discuss the prognostic correlation between hepatitis B virus DNA (HBV DNA) level and HBV-related hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI).Data from HCC patients undergoing hepatectomy with pathological evidence of MVI were retrospectively collected and 1:1 propensity scoring matching (PSM) analysis was performed. According to the HBV DNA levels before and after surgery, the disease-free survival (DFS) and overall survival (OS) were evaluated using the Kaplan-Meier method, and the Cox proportional hazards regression was used to analyze the risk factors associated with the postoperative prognosis. After 1:1 PSM, 139 pairs of patients were enrolled in the high preoperative HBV DNA level group (H group) and low preoperative HBV DNA level group (L group), and after operation, patients with high preoperative HBV DNA levels were divided into the persistently high HBV DNA level group (P group) and the decreased HBV DNA level group (D group).According to the multivariate analysis, the HBV DNA level of 2000 IU/ml or greater before operation was significantly associated with the DFS (hazard ratio, 1.322; 95%CI, 1.016-1.721) and OS (hazard ratio, 1.390; 95%CI, 1.023-1.888). A persistent HBV DNA level of 2,000 IU/ml or greater after operation was also the independent risk factor of DFS (hazard ratio, 1.421; 95%CI, 1.018-1.984) and OS (hazard ratio, 1.545; 95%CI, 1.076-2.219).For the HBV-related HCC patients with MVI, preoperative high HBV DNA copies are prognostication of poorer prognosis, and effective antivirus treatment would significantly improve the patients' prognosis.

LncRNA MIR210HG promotes proliferation and invasion of non-small cell lung cancer by upregulating methylation of CACNA2D2 promoter via binding to DNMT1.

Background: In recent years, a large number of studies have shown that differentially expressed lncRNAs are capable of promoting the occurrence and development of tumors by regulating cell proliferation and differentiation. However, the biological effects of lncRNAs in non-small cell lung cancer (NSCLC) are still needed to be further investigated.Methods: The differentially expressed lncRNAs in NSCLC tissues in the downloaded profiles from GEO database were analyzed and further verified in 100 pairs of NSCLC samples collected in our hospital. After identification of the target gene MIR210HG, the relationship between MIR210HG expression and clinical data of NSCLC patients was analyzed. Regulatory effects of MIR210HG on proliferation, migration, and invasion of NSCLC cells were detected by CCK-8, colony formation, and transwell assay, respectively. The binding condition of MIR210HG and DNA methyltransferase 1 (DNMT1) was detected by RNA binding protein immunoprecipitation. Subsequently, chromatin immunoprecipitation assay assessed the promoter binding of DNMT1 to CACNA2D2. Rescue experiments were conducted to assess whether CACNA2D2 can reverse the function of MIR210HG.Results: MIR210HG was highly expressed in NSCLC tissues not only in GSE30219 dataset but also in our collected NSCLC tissues. MIR210HG expression was correlated to tumor stage and lymph node metastasis of NSCLC patients. Besides, lower disease-free survival (DFS) and overall survival (OS) were found in NSCLC patients with high-level MIR210HG compared with those with low-level MIR210HG. Regression analysis indicated that MIR210HG was the independent risk factor for DFS and OS of NSCLC patients. In vitro experiments demonstrated that MIR210HG knockdown remarkably inhibited proliferation and migration of NSCLC cells. MIR210HG could recruit DNMT1, thereafter promoting methylation of CACNA2D2 promoter region. CACNA2D2 overexpression remarkably inhibited cell proliferation. Moreover, inhibited proliferation induced by MIR210HG knockdown was reversed by CACNA2D2 knockdown.Conclusion: MIR210HG can promote the tumorigenesis of NSCLC by inhibiting the expression of CACNA2D2. Our findings provide new therapeutic strategies for the future treatment of NSCLC.

Prognostic factors for disease-free survival in patients with pancreatic ductal adenocarcinoma after surgery: a single center experience

Abstract Objective: To evaluate the risk factors for the disease-free survival (DFS) of pancreatic ductal adenocarcinoma (PDAC) patients after surgery, and to validate the clinical applicability and prognostic stratification of the 8th edition American Joint Committee on Cancer (AJCC) staging system. Methods: A cohort of 185 patients with PDAC who underwent surgical resection in the General Surgery Department of Peking University First Hospital from January 2010 to December 2017 was enrolled retrospectively. The clinicopathological characteristics and survival data were analyzed to find out risk factors correlated to DFS. The survival curves were calculated according to the 8th edition of AJCC staging system. Results: Among the 185 PDAC patients, 125 (67.6%) with pancreatic head carcinoma underwent pancreatoduodenectomy or total pancreatectomy, and 60 (32.4%) with tumors located in the pancreatic body and tail underwent distal pancreatectomy and splenectomy. R0 resection was achieved in 97 patients (52.4%), and the R1 and R2 resections rate was 44.9% and 2.7%, respectively. One hundred five patients (56.8%) received postoperative adjuvant chemotherapy. The median overall survival (OS) was 21 (95% confidence interval [CI] 17.7–24.3) months, and median DFS was 15 (95% CI 13.6–16.5) months. Univariate analysis showed that AJCC T and N staging, status of resection margin, grade of tumor differentiation, perineural invasion, intravascular cancer embolus, combined vascular resection, neutrophil-to-lymphocyte ratio (NLR) ≥ 2, carcinoembryonic antigen ≥5 ng/mL, carbohydrate antigen 19-9 (CA 19-9) ≥ 400 U/mL, and without postoperative adjuvant chemotherapy were correlated with shorter DFS. Furthermore, AJCC T3, N1 and N2 staging, R2 resection, low-grade or undifferentiated tumors, combined vascular resection, NLR ≥ 2, CA 19-9 ≥ 400 U/mL, and without postoperative adjuvant chemotherapy were independent risk factors for DFS. Both the DFS and OS curves were well separated by stage using the 8th staging classification. Conclusions: The 8th edition of AJCC T, primary tumor; N, regional lymph nodes; M, distant metastasis staging system could predict the prognosis of PDAC accurately. Patients with AJCC T3, N1 and N2 staging, R2 resection, low-grade or undifferentiated tumors, combined vascular resection, NLR ≥ 2, CA 19-9 ≥ 400 U/mL, and without postoperative adjuvant chemotherapy, have a significantly higher risk of tumor recurrence and shorter DFS after surgery. R0 resection and adjuvant chemotherapy could significantly prolong the DFS of PDAC patients.