Aggressive Clinicopathological Features Research Articles

Clinical implication of minimal presence of solid or micropapillary subtype in early-stage lung adenocarcinoma.

BackgroundWe investigated the clinical features and surgical outcomes of lung adenocarcinoma with minimal solid or micropapillary (S/MP) components, with a focus on stage IA.MethodsWe enrolled 506 patients with lung adenocarcinoma who underwent curative resection in this study. Clinical features and surgical outcomes were compared between the groups with and without the S/MP subtype (S/MP+ and S/MP−, respectively), and between the group with an S/MP proportion of ≤5% (S/MP5) and the S/MP−.ResultsThe S/MP subtype was present in 247 patients (48.8%); 129 (25.5%) were grouped as the S/MP5 group. The S/MP+ and S/MP5 groups had larger tumors, higher frequency of lymph node metastasis, and more advanced stages of disease than the S/MP− group (P < 0.001, all comparisons). Pleural, lymphatic, and vascular invasions occurred more frequently in the S/MP+ and S/MP5 groups (P < 0.001, all comparisons for S/MP+ vs. S/MP−; P ≤ 0.01, all comparisons for S/MP5 vs. S/MP−). The S/MP+ and S/MP5 groups showed a shorter time to recurrence and cancer‐related death than the S/MP− group(P < 0.001, both comparisons). For stage I, the presence or absence of the S/MP subtype defined prognostic subgroups better than the stage IA/IB classification. Notably, in the multivariate analysis, the minimal S/MP component was a significant predictor of recurrence, even in stage IA.ConclusionsThe presence of the minimal S/MP component was a significant predictor of poor prognosis after surgery, even in stage IA patients. Clinical trials to evaluate the advantages of adjuvant chemotherapy for this subset of patients and further investigations to understand underlying biological mechanisms of poor prognosis are needed.Key pointsSignificant findings of the study: We demonstrated that only minimal presence of solid or micropapillary component was profoundly associated with aggressive clinicopathological features and poor prognosis after complete resection even in stage IA lung adenocarcinoma. What this study adds: Our results suggest that minimal presence of these subtypes is a strong prognostic factor which should be taken into account in the risk assessment for adjuvant chemotherapy in lung adenocarcinoma.

MicroRNAs expression associated with aggressive clinicopathological features and poor prognosis in primary cutaneous melanomas.

Several studies have focused on identifying microRNAs involved in the pathogenesis of melanoma. However, its association with clinicopathological features has been scarcely addressed. The aim of this study is to identify microRNAs expression profiles related to aggressive clinicopathological and molecular features, and to analyze the association with melanoma survival. A retrospective and observational study was performed in a series of 179 formalin-fixed paraffin embedded primary cutaneous melanomas. First, a screening analysis on a discovery set (n = 22) using miRNA gene chip array (Affymetrix, Santa Clara, California, USA) was performed. Differentially expressed microRNAs were detected employing the software Partek Genomic Suite. Validation of four microRNAs was subsequently performed in the entire series (n = 179) by quantitative real time PCR (qRT-PCR). MicroRNAs expression screening analysis identified 101 microRNAs differentially expressed according to Breslow thickness (≤1 mm vs. >1 mm), 79 according to the presence or absence of ulceration, 78 according to mitosis/mm2 (<1 mitosis vs. ≥1 mitosis) and 97 according to the TERT promoter status (wt vs. mutated). Six microRNAs (miR-138-5p, miR-130b-3p, miR-30b-5p, miR-34a-5p, miR-500a-5p, miR-339-5p) were selected for being validated by qRT-PCR in the discovery set (n = 22). Of those, miR-138-5p, miR-130b-3p, miR-30b-5p, miR-34a-5p were selected for further analysis in the entire series (n = 179). Overexpression of miR-138-5p and miR-130b-3p was significantly associated with greater Breslow thickness, ulceration, and mitosis. TERT mutated melanomas overexpressed miR-138-5p. Kaplan-Meier survival analysis showed poorer survival in melanomas with miR-130b-3p overexpression. Our findings provide support for the existence of a microRNA expression profile in melanomas with aggressive clinicopathological features and poor prognosis.

A novel circular RNA circ-LRIG3 facilitates the malignant progression of hepatocellular carcinoma by modulating the EZH2/STAT3 signaling

BackgroundCircular RNA (circRNA) is emerging as an important player in human diseases, especially cancer. In our previous study, we identified a series of deregulated circRNAs in hepatocellular carcinoma (HCC) by performing circRNA microarray expression profile. Here, we aimed to explore the role of circ-LRIG3 (hsa_circ_0027345) in HCC.MethodsqRT-PCR and western blot were used to asses gene and protein expression, respectively. CCK-8, EdU and Transwell assays were used to detect cell proliferation, migration and invasion. GSEA software was applied to analyze the pathway related to circ-LRIG3. Co-IP, RIP and ChIP assays were used to identify the positive feedback axis of circ-LRIG3/EZH2/STAT3. Animal study was carried to test the role of circ-LRIG3 in vivo.ResultsCirc-LRIG3 was notably upregulated in HCC and promoted HCC cell proliferation, migration, invasion and reduced apoptosis. Circ-LRIG3 formed a ternary complex with EZH2 and STAT3, facilitating EZH2-induced STAT3 methylation and subsequent phosphorylation, resulting in the activation of STAT3 signaling. In turn, activated STAT3 could directly bind to circ-LRIG3 promoter to increase circ-LRIG3 transcription activity, thus forming a positive feedback loop. The animal models showed that exogenous expression of circ-LRIG3 enhanced tumorigenicity and metastasis in vivo, whereas these effects were blocked after treatment with C188–9, a specific STAT3 small-molecule inhibitor. Clinically, high circ-LRIG3 was closely linked with aggressive clinicopathological features and was identified as an independent risk prognostic factor of overall survival. Importantly, plasma circ-LRIG3 was found to be a highly sensitive and specific non-invasive diagnostic indicator for HCC.ConclusionsOur study reveals the carcinogenic role of circ-LRIG3 in HCC, which may provide a new therapeutic target for HCC patients.

The Impact of Circulating Tumor Cells on Venous Thromboembolism and Cardiovascular Events in Bladder Cancer Patients Treated with Radical Cystectomy.

Background: Cancer is a relevant risk factor for venous thromboembolism (VTE). Circulating tumor cells (CTC) are associated with an increased risk of VTE in breast cancer. In addition, circulating cell-free nucleic acids have been associated with cardiovascular events (CVE). Objective: To investigate the association of CTC status and the risk of VTE as well as CVE in urothelial carcinoma of the bladder (UCB) patients treated with radical cystectomy (RC). Methods: We collected data of 189 UCB patients treated with RC at our institution. Blood samples were acquired preoperatively and analyzed for CTC using the CellSearch® system. Thirty-day postoperative complications were extracted from digital charts and graded according to the Clavien–Dindo classification (CDC). Moreover, each patient’s individual Comprehensive Complication Index® (CCI®) was calculated. Results: CTC were present in 43 patients (22.8%). Overall, six patients experienced VTE (3.2%) and eight patients (4.2%) experienced CVE. There was no association of VTE or CVE according to CTC status. In total, 168 patients (89%) experienced a total of 801 complications, of which the majority was classified as “minor” (CDC grade ≤ IIIa; 79%). There was no association between CTC status and any grade of a complication or CCI®. Presence of CTC was associated with more aggressive clinicopathological UCB features. Conclusions: The overall rate of VTE and CVE was low in our study. Presence of CTC was neither associated with an increased risk of VTE nor CVE in UCB patients treated with RC. According to this study, CTC are not a qualified biomarker for individualized thromboprophylaxis management in these patients.

Influence of Tumor Number on Clinicopathologic Features and Outcomes of Patients With Papillary Thyroid Carcinoma

The purpose of this study was to investigate the significance of tumor number on clinicopathologic factors and outcomes of patients with papillary thyroid carcinoma (PTC). We retrospectively analyzed 667 patients with PTC. We compared clinicopathologic features of patients with a different tumor number. Cox proportional hazards model was used to analyze risk factors of recurrence. In papillary thyroid microcarcinoma (PTMC), the increase in the number of tumor foci was related to a higher risk of minimal extrathyroidal extension (ETE) and lymphovascular invasion (P < .05). Patients with PTMC with four or more foci had a significantly higher risk of central lymph node metastasis (CLNM) and lateral lymph node metastasis (LLNM) than patients with solitary tumors (P < .05). Patients with macro-PTC with four or more foci and with three foci had a higher risk of gross ETE and lymphovascular invasion than patients with solitary tumors (P < .05). The increase in the tumor number was related to a higher risk of CLNM in macro-PTC (P < .05). The number of foci was the independent predictor of recurrence in patients with macro-PTC (P < .05). An increase in the number of tumors was associated with an increased risk of aggressive clinicopathologic features in PTMC and macro-PTC. The number of tumor foci could influence risk of recurrence in macro-PTC.

Mutations of the TERT promoter are associated with aggressiveness and recurrence/distant metastasis of papillary thyroid carcinoma.

Several previous studies have shown that mutations in B-Raf proto-oncogene (BRAF) and telomerase reverse transcriptase (TERT) can be used for the diagnosis and prognosis of papillary thyroid carcinoma (PTC). However, whether mutations in BRAF and the TERT promoter may improve the accurate identification and risk stratification of high-risk patients in the early stage of PTC remains unclear and requires further investigation. In the present study, mutations in BRAF and the TERT promoter were examined in 205 patients using PCR and Sanger DNA sequencing. The potential association between mutations in these two genes and the clinicopathological characteristics of patients with PTC was then analyzed. BRAF mutations were identified in 169/205 (82.4%) patients, whereas only 8/205 (3.9%) patients presented mutations in the TERT promoter, seven patients exhibited a C228T mutation, and the remaining one had a C250T mutation. There were 6/205 (2.9%) patients with mutations in both BRAF and the TERT promoter. Importantly, compared with patients with no mutations, patients with mutations in BRAF were more likely to exhibit mutations in the TERT promoter. A significant difference in lymph node metastasis was found between the BRAF V600E mutation group and the group without mutations in BRAF. Mutations in the TERT promoter were significantly correlated with older age, extrathyroidal invasion, tumor multifocality and advanced tumor/node/metastasis stage, which are associated with the aggressiveness of PTC. Moreover, compared with patients exhibiting mutations in BRAF, mutations in the TERT promoter were found to be significantly associated with aggressive clinicopathological features and higher risk of recurrence or distant metastasis. Collectively, mutations in the TERT promoter were not frequent, but were significantly correlated with more aggressive clinicopathological features of PTC. Therefore, mutations in the TERT promoter may be an important factor in the genetic background of PTC, and detection of such mutations may help the accurate identification and management of high-risk patients with recurrent or distant metastasis.

SIRT2, a direct target of miR-212-5p, suppresses the proliferation and metastasis of colorectal cancer cells.

The aberrant expression of human sirtuin 2 (SIRT2) has been detected in various types of cancer; however, the biological roles, underlying mechanisms and clinical significance of SIRT2 dysregulation in human colorectal cancer (CRC) remain unclear. The results of this study demonstrate that compared with paired normal tissues, SIRT2 expression is significantly decreased in CRC tissues. SIRT2 loss has been correlated with clinicopathological characteristics, including distant metastasis, lymph node metastasis and American Joint Committee on Cancer (AJCC) stage; this loss serves as an independent factor that indicates a poor prognosis for patients with CRC. Further gain‐ and loss‐of‐function analyses have demonstrated that SIRT2 suppresses CRC cell proliferation and metastasis both in vivo and in vitro. Mechanistically, miR‐212‐5p was identified to directly target the SIRT2 3′‐untranslated region (3′‐UTR), leading to SIRT2 down‐regulation. The ectopic expression of SIRT2 reverses the effect of miR‐212‐5p overexpression on CRC cell colony formation, invasion, migration and proliferation. Clinically, an inverse correlation was found between miR‐212‐5p and SIRT2 expression. High miR‐212‐5p expression has been found to result in a poor prognosis and aggressive clinicopathological characteristics in patients with CRC. Taken together, these results suggest that SIRT2, targeted by miR‐212‐5p, acts as a tumour suppressor in CRC and that the miR‐212‐5p/SIRT2 axis is a promising prognostic factor and potential therapeutic target in CRC.

MASTL: A novel therapeutic target for Cancer Malignancy.

Targeting mitotic kinases is an emerging anticancer approach with promising preclinical outcomes. Microtubule‐associated serine/threonine kinase like (MASTL), also known as Greatwall (Gwl), is an important mitotic kinase that regulates mitotic progression of normal or transformed cells by blocking the activity of tumor suppressor protein phosphatase 2A (PP2A). MASTL upregulation has now been detected in multiple cancer types and associated with aggressive clinicopathological features. Apart, an aberrant MASTL activity has been implicated in oncogenic transformation through the development of chromosomal instability and alteration of key oncogenic signaling pathways. In this regard, recent publications have revealed potential role of MASTL in the regulation of AKT/mTOR and Wnt/β‐catenin signaling pathways, which may be independent of its regulation of PP2A‐B55 (PP2A holoenzyme containing a B55‐family regulatory subunit). Taken together, MASTL kinase has emerged as a novel target for cancer therapeutics, and hence development of small molecule inhibitors of MASTL may significantly improve the clinical outcomes of cancer patients. In this article, we review the role of MASTL in cancer progression and the current gaps in this knowledge. We also discuss potential efficacy of MASTL expression for cancer diagnosis and therapy.

Prevalence of autoantibodies against Ras-like GTPases, RalA, in patients with gastric cancer.

Ras-like GTPases, RalA and RalB, are members of the Ras superfamily of small GTPases. RalA expression has been shown to be associated with aggressive clinicopathological characteristics and progression in cancer. RalA protein has been shown to be involved in immune reactions in some patients with cancer; however, the clinicopathological significance of serum RalA antibody in patients with gastric cancer has not been investigated. Serum samples of 291 patients with gastric cancer and 73 healthy controls were analyzed for serum RalA antibody using enzyme-linked immunosorbent assay. A cut-off optical density value was fixed at 0.255 (mean of control + 2 standard deviations). The clinicopathological and prognostic significance of s-RalA-Abs was evaluated. The positivity rate for serum RalA antibody (s-RalA-Abs) was 15%. The presence of serum RalA antibody was higher in younger patients compared with elderly patients, however this tendency was not statistically significant. s-RalA-Abs was not associated with tumor stage. Since s-RalA-Abs was independent of CEA (carcinoembryonic antigen) and carbohydrate antigen 19-9 (CA19-9), the combination of s-RalA-Abs with CEA and CA19-9 significantly increased the detection rate of gastric cancer at each tumor stage. Patients who were tested positive for s-RalA-Abs showed poor long-term survival; however, this association was not statistically significant by multivariate analysis. In conclusion, s-RalA-Abs may be a candidate serum marker for gastric cancer, when used in combination with CEA and/or CA19-9. Additionally, the presence of s-RalA-Abs, in combination with CEA and/or CA19-9, was associated with poor survival in patients with gastric cancer.

SMYD3 overexpression indicates poor prognosis and promotes cell proliferation, migration and invasion in non‑small cell lung cancer.

SET and MYND domain-containing protein 3 (SMYD3) is a lysine methyltransferase, and its aberrant expression has been implicated in several malignancies. However, its clinical and biological roles in non-small cell lung cancer (NSCLC) remain unclear. In the present study, it was revealed that SMYD3 was significantly upregulated in NSCLC tissues, as compared with paired adjacent normal tissues. A high SMYD3 expression was associated with aggressive clinicopathological characteristics, as well as poor disease-free survival and overall survival (OS) in NSCLC patients. Multivariate analysis revealed that SMYD3 overexpression was an independent predictor of poor OS in NSCLC patients. In addition, SMYD3 knockdown inhibited cell proliferation, triggered apoptosis, and blocked migration and invasion in NSCLC cells in vitro, whereas stable SMYD3 overexpression promoted NSCLC cell proliferation. Furthermore, the SMYD3-silenced NSCLC cells became more sensitive, whereas the SMYD3-overexpressed NSCLC cells became more resistant to the apoptosis induced by cisplatin. Mechanistic analysis revealed that SMYD3 knockdown led to the upregulation of Bim, Bak and Bax, and the downregulation of Bcl-2, Bcl-xl, MMP-2 and MMP-9 in NSCLC cells. In combination, the present findings indicated that SMYD3 has oncogenic potential in the context of NSCLC, providing evidence that may be exploited for both prognostic and therapeutic purposes in the future.

328 - PD-L1 expression was associated with aggressive clinicopathological features in patients with VHL-related renal cell carcinoma

328 - PD-L1 expression was associated with aggressive clinicopathological features in patients with VHL-related renal cell carcinoma

NOVA1 expression is associated with clinicopathological characteristics and prognosis in patients with small cell lung cancer.

BackgroundSmall cell lung cancer (SCLC) is a highly aggressive lung malignancy which is characteristic of rapid tumor proliferation, metastasis as well as paraneoplastic neurological syndromes (PNS). Recent studies have shown that neuro-oncological ventral antigen-1 (NOVA1) plays a crucial role in the progression of various tumors. However, its effect on SCLC is still exclusive. This study was aimed to explore NOVA1 expression in tumor tissues of SCLC patients as well as its correlation with clinicopathological characteristics and cancer-specific overall survivals.MethodsIn this study, the patients pathologically diagnosed with new primary SCLC were enrolled. Firstly, we compared NOVA1 expression in SCLC tissues and adjacent normal tissues by immunohistochemistry. We further investigated the association of NOVA1 expression with clinicopathological markers (especially the categories of PNS) and survival time in SCLC patients.ResultsOur finding exhibited that NOVA1 was remarkably expressed in SCLC tumorous tissues compared with adjacent normal lung tissues (P<0.001). Additionally, NOVA1 expression was closely associated with clinicopathological characteristics in SCLC patients in terms of tumor staging(χ2=15.833; P<0.001), lymph node metastasis (χ2=9.624; P=0.002), brain metastasis (χ2=9.624; P=0.002) and PNS (χ2=5.004; P=0.024). With the COX proportional hazard regression model, we detected that high expression of NOVA1 (HR =0.445; 95% CI: 0.213–0.934; P=0.032) was an independent factor for shorter survival time.ConclusionsHigh expression of NOVA1 is closely associated with aggressive clinicopathological characteristics including PNS as well as poor survival in SCLC patients. NOVA1 can be served as a promising predictive factor for prognosis in SCLC.

Characteristic and clinical significance of microRNA expression between 144 Uygur and Han women with endometrial carcinoma

To compare the expression patterns of microRNA (miRNA) between 144 Uygur and Han women with endometrial carcinoma and to investigate their clinical significance. Taqman miRNA low-density array was used to compare miRNA profiles between Uygur and Han women with non-endometrioid endometrial carcinoma (NEEC). Five miRNAs were further analyzed in the 144 endometrial cancers including 62 Uygur and 82 Han samples via real-time PCR to determine their expression patterns. MiRNA expression profiles revealed that many miRNAs overexpressed or downregula-ted in one ethnic group, but did not express or changed slightly in the other ethnic group. Further detection in the 144 endometrial cancers showed that miR-141, miR-200a, and miR-205 overexpressed in both ethnic groups. In Uygur endometrioid endometrial carcinoma (EEC), tumors with miR-141/200a overexpression tended to be more aggressive in behavior, whereas in the Han group, EEC with miR-200a overexpression was relative mild. However, the NEEC with miR-200a overexpression also had aggressive clinicopathologic features in the Han women. MiR-145 and miR-143 expressed differentially between Uygur and Han groups, they overexpressed in the former and decreased in the latter (P<0.05). In the Uygur women miR-145/143 increased significantly in NEEC and there was a trend that NEEC exhibiting favorable clinicopathologic factors had higher miR-145 expression, and was statistically significant in tumors with myometrial invasion less than 1/2 thickness (P=0.042). By contrary, miR-145/143 decreased in Han group and EEC with worse clinicopathologic variables had lower expression although without statistical significance. NEEC in Han group had no such tendency. Uygur and Han women might have different miRNA expression profiles. MiR-141/200a/205 overexpressed in endometrial carcinomas and miR-141/200a might behave differently between these two ethnic groups as well as in EEC and in NEEC. Although miR-145/143 showed inverse expression patterns between Uygur and Han women with endometrial cancer, they all exerted tumor suppression effect on endometrial cancer.

FOXC2 is a prognostic biomarker and contributes to the growth and invasion of human hepatocellular carcinoma

BackgroundForkhead box C2 (FOXC2) is a crucial factor involving in various cancers. However, its functions in hepatocellular carcinoma (HCC) is unknown. Here, we explored the role of FOXC2 in the progression of HCC and its potential mechanisms.MethodsFOXC2 expression in HCC tissue and cells were detected by immunohistochemistry or western blot and real-time PCR. CCK8, wound healing and transwell assay were used to measure cell growth and invasion. Tumor formation experiment was carried out to assess the tumorigenicity of HCC cells. Regulation of FOXC2 on Ang-2 was validated by luciferase assay and complementary experiments.ResultsIncreased FOXC2 expression was found to be associated positively with more aggressive clinicopathologic features. HCC patients with higher FOXC2 expression had significantly shorter overall survival. FOXC2 expression was indentified as an independent risk factor for resectable HCC. Increased FOXC2 expression accelerated the migration and invasion of HCC cells, accompanied by enhanced Ang-2 expression. Likewise, FOXC2 knockdown yielded opposite results. Moreover, FOXC2 stimulated the activation of the Ang-2 promoter. Suppression of Ang-2 expression hindered the FOXC2-mediated EMT processs, cell migration and invasion of HCC.ConclusionsFOXC2 is a novel prognostic predictor for HCC and may facilitate the growth and invasion through Ang-2.

44P Obesity is associated with a late-stage diagnosis in triple-negative breast cancer

Approximately one third of breast cancer (BC) patients are obese, a fact that has been associated with an increased frequency of aggressive clinicopathological features and worse disease outcomes. The aim of this study was to evaluate if obesity plays a selective role in disease stage according to molecular subtype.

XRCC1 Is a Promising Predictive Biomarker and Facilitates Chemo-Resistance in Gallbladder Cancer.

Gallbladder cancer is a relatively uncommon human malignant tumor with an extremely poor prognosis. Currently, no biomarkers can accurately diagnose gallbladder cancer and predict patients’ prognosis. XRCC1 is involved in tumorigenesis, progression, and chemo-resistance of several human cancers, but the role of XRCC1 in gallbladder cancer is never reported. In this study, we investigated the expression of XRCC1 and its clinicopathological and prognostic significance in gallbladder cancer, and explored the biological role of XRCC1 in gallbladder cancer cells. We found that XRCC1 was significantly up-regulated in gallbladder cancer in protein and mRNA levels. Positive XRCC1 expression was correlated with aggressive clinicopathological features and was an independent poor prognostic factor in gallbladder cancer. The ROC curves suggested that XRCC1 expression had potential clinicopathological diagnostic value in gallbladder cancer. In vitro, XRCC1 was overexpression in CD133+GBC-SD cells compared to GBC-SD cells. In functional experiment, XRCC1 knockdown had a non-significant impact on proliferation, migration, invasion, and apoptosis of CD133+GBC-SD cells. But, XRCC1 knockdown could significantly improve the sensitivity of CD133+GBC-SD cells to 5-Fluorouracil via promoting cell necrosis and apoptosis. Thus, this study indicates that XRCC1 may be a promising predictive biomarker of gallbladder cancer and a potential therapeutic target for gallbladder cancer.

Clinicopathological implications of the expression of vascular endothelial growth factor and programmed death ligand 1 in clear-cell renal cell carcinoma

Combined anti-VEGF/anti-programmed death ligand 1 (PD-L1) therapy synergistically improves treatment outcomes in advanced renal cell carcinoma (RCC) compared with anti-PD-L1 or anti-vascular endothelial growth factor (VEGF) monotherapy. Here, we analyzed the expression of VEGF and PD-L1 (SP142) in a retrospective cohort of 513 patients with clear-cell (cc) RCC. PD-L1 expression on tumor cells (TCs) and immune cells (ICs) was evaluated by immunohistochemistry (IHC) with a positive threshold value of ≥1%. Positive staining for PD-L1 on ICs and TCs was found in 115 (22.4%) and 7 (1.4%) cases, respectively. Moderate or strong staining for VEGF on TCs was found in 217 (42.3%) patients. PD-L1 expression on ICs and TCs was positively associated with VEGF expression on TCs. Both VEGF and PD-L1 (IC) positivity (VEGF/PD-L1 [IC]: +/+) was observed in 65 (12.7%) cases. Patients in this subgroup exhibited more aggressive clinicopathologic features, including older age, higher World Health Organization/International Society of Urological Pathology(ISUP) grade, angiolymphatic invasion, tumor necrosis, and sarcomatoid differentiation (P<0.05). Kaplan-Meier analysis indicated that expression of VEGF and PD-L1 on ICs was positively correlated with tumor recurrence (P<0.001), whereas expression of PD-L1 on TCs was not (P=0.554). Tumors with positivity for both antibodies (VEGF/PD-L1 [IC]: +/+) exhibited the worst recurrence-free survival (P<0.001), and double positivity independently predicted tumor recurrence in ccRCC. The present study provides comprehensive and basic information about VEGF and PD-L1 expression for new combined therapy in primary ccRCC.

MicroRNA-95-3p inhibits cell proliferation and metastasis in colorectal carcinoma by HDGF

BackgroundMicroRNAs (miRNAs) play an important regulatory role in carcinogenesis and cancer progression. MiR-95-3p has been reported to be an oncogene in hepatocellular carcinoma. However, the role of miR-95-3p in colorectal carcinoma (CRC) remains unclear. MethodsmiR-95-3p was validated in an independent validation sample cohort of 215 CRC tissues. Functional assays, Cell proliferation (MTT) assay colony formation, wound healing, transwell and animal xenograft assays were used to determine the oppressor role of miR-95-3p in human CRC progression. Furthermore, Bioinformatics analysis, western blotting and dual-luciferase reporter assay were used to determine the mechanism by which miR-95-3p suppresses progression of CRC cells. ResultsIn this study, we found that miR-95-3p was downregulated in CRC tissues. The low level of miR-95-3p in CRC tumors was correlated with aggressive clinicopathological characteristics, and it predicted poor prognosis in CRC patients. The overexpression of miR-95-3p significantly inhibited CRC cell proliferation, colony formation and metastasis in vitro and in vivo. Bioinformatic analysis further identified hepatoma-derived growth factor (HDGF) as a novel target of miR-95-3p in CRC cells. These findings suggest that miR-95-3p regulates CRC cell survival, partially through the downregulation of HDGF. ConclusionsTherefore, the miR-95-3p/HDGF axis might serve as a novel therapeutic target in patients with CRC.

Association Between EphA1 and Tumor Microenvironment in Gastric Carcinoma and its Clinical Significance.

BackgroundWith the growing global burden of gastric carcinoma (GC) and the urgent need for biomolecular targeted therapies, this study aimed to elucidate the relationship between EphA1 and the tumor microenvironment (focusing primarily on the key inflammatory cytokines IL-6 and tumor angiogenic cytokine VEGF) to identify a new potential therapeutic target.Material/MethodsIHC and qRT-PCR were performed to quantify the protein and gene expression levels of EphA1, IL-6, and VEGF in normal mucosal tissues, carcinoma tissues, and paracarcinomatous tissues from 57 GC patients. Spearman’s rank correlation test was performed to determine the relationship between EphA1, IL-6, and VEGF expression levels. The relationships of EphA1 with clinicopathologic parameter and survival in GC patients were also evaluated.ResultsThe protein and gene expression levels of EphA1 were all attenuated gradually from carcinoma tissues to paracarcinomatous tissues and then to normal mucosal tissues in GC patients. Additionally, significant correlations between the overexpression of EphA1 with aggressive clinicopathological features and shorter survival time of GC patients were verified. In particular, we found a significant positive correlation between the expression of EphA1 and tumor microenvironment hallmark proteins IL-6 and VEGF in carcinoma tissues and paracarcinomatous tissues.ConclusionsEphA1 can promote the occurrence and development of GC by its selective high expression in cancer tissues and its relationship with malignant clinical features and prognosis of GC patients. The underlying potential mechanism appears to involve enhancement of the tumor microenvironment, which via drives the expression of tumor microenvironment hallmark proteins IL-6 and VEGF.

Influence of body mass index on the clinicopathological features of 13,995 papillary thyroid tumors.

This retrospective study aimed to assess the association between obesity, gender, and specific clinicopathological features in patients with papillary thyroid cancer (PTC) and whether diagnostic ultrasonography (US) is adversely affected by obesity in these patients. This study retrospectively analyzed 13,995 adult patients with PTC from a single medical center in China. Data stratification was performed to assess the association of obesity with US features and aggressive clinicopathological features in different models according to the World Health Organization Body Mass Index (WHO-BMI) and Chinese BMI classification (CN-BMI). The odds ratio (OR) of malignant US features and aggressive clinicopathological features was calculated from binary logistic regression models. The BMI, obesity ratio, malignant US features, and aggressive pathological characteristics of males were significantly higher than those of females. After adjusting for confounding factors, the association of obesity with malignant US features and aggressive pathological characteristics was found to be sex-dependent. Next, obesity (WHO-BMI) was found to have an "interfering effect" on the US assessment of PTC (OR = 0.754, 95% CI 0.609-0.932, P = 0.009) in women. Among both sexes, obesity (WHO-BMI) increased the risk of tumor size (ORmale = 1.539 and ORfemale = 1.521) and multifocality (ORmale = 1.659 and ORfemale = 1.449). However, obesity did not increase the risk of capsular invasion or tumor staging in males. The above results are consistent with the CN-BMI. In addition, age was found to have an "interfering effect" on the US evaluation of malignant nodules in both sexes. The results of our study confirm that higher BMI is significantly associated with aggressive clinicopathological features of PTC. Gender differences were present with obesity ratios and aggressive clinicopathological features being significantly higher in men.