Cancer-testis antigen KK-LC-1 is a potential biomarker associated with immune cell infiltration in lung adenocarcinoma.

BACKGROUND: Cancer-testis antigens (CTAs) have emerged as potential clinical biomarkers targeting immunotherapy. KK-LC-1 is a member of CTAs, which has been demonstrated in a variety of tumors tissues and been found to elicit immune responses in cancer patients. However, the expression level and immune infiltration role of KK-LC-1 in lung adenocarcinoma (LUAD) remains to be elucidated. METHODS: In this study, the mRNA expression and overall survival rate of KK-LC-1 were evaluated by the TIMER and TCGA database in LUAD tissues and KK-LC-1 expression was further validated by clinical serum samples using quantitative RT-PCR. The relationship of KK-LC-1 with clinicopathologic parameters was analyzed. ROC curve result showed that miR-1825 was able to distinguish preoperative breast cancer patients from healthy people and postoperative patients. Then, the ROC curves were used to examine the ability of KK-LC-1 to distinguish preoperative LUAD patients from healthy and postoperative patients. The correlation between KK-LC-1 and infiltrating immune cells and immune marker sets was investigated via TIMER, TISIDB database, and CIBERSORT algorithm. The Kaplan-Meier plotter was used to further evaluate the prognostic value based on the expression levels of KK-LC-1 in related immune cells. RESULTS: The results showed that KK-LC-1 was significantly over-expressed in LUAD, and high levels of expression of KK-LC-1 were also closely correlated with poor overall survival. We also found that KK-LC-1 associated with TMN stage, NSE and CEA. The ROC curve result showed that KK-LC-1 was able to distinguish preoperative LUAD cancer patients from healthy people and postoperative patients. Moreover, KK-LC-1 had a larger AUC with higher diagnostic sensitivity and specificity than CEA. Based on the TIMER, TISIDB database, and CIBERSORT algorithm, the expression of KK-LC-1 was negatively correlated with CD4+ T cell, Macrophage, and Dendritic Cell in LUAD. Moreover, Based on the TIMER database, KK-LC-1 expression had a remarkable correlation with the type markers of Monocyte, TAM, M1 Macrophage, and M2 Macrophage. Furthermore, KK-LC-1 expression influenced the prognosis of LUAD patients by directly affecting immune cell infiltration by the Kaplan-Meier plotter analysis. CONCLUSIONS: In conclusion, KK-LC-1 may serve as a promising diagnostic and prognostic biomarker in LUAD and correlate with immune infiltration and prognosis.

Plasma Exosomal CXCL7 is a Potential Biomarker for Lung Adenocarcinoma.

BACKGROUND: Lung cancer is a leading cause of cancer-related death, with lung adenocarcinoma (LUAD) representing the most common subtype. Recently, exosome-based biomarkers have provided new diagnostic approaches for malignancies. METHODS: The differential expression profile of plasma exosomal mRNA was established by high-throughput sequencing, and the expression and diagnostic value of plasma exosomal CXCL7 mRNA and protein in LUAD were studied to evaluate their diagnostic value as tumor biomarkers. RESULTS: The expression of plasma exosomal CXCL7 mRNA in patients with LUAD was significantly increased (p < 0.01), which had no significant correlation with age, gender, and stage. ROC was used to evaluate the diagnostic value of plasma exosomal CXCL7 mRNA in LUAD patients with AUC = 0.7171. Further analysis signified that the CXCL7 protein of plasma exosomes in LUAD patients was overexpressed, and it was positively correlated with TNM stage and age. The diagnostic value of plasma exosomal CXCL7 in LUAD is better than serum CEA, with an AUC of 0.785, which has higher sensitivity and specificity. CONCLUSIONS: This research suggests that plasma exosomal CXCL7 may become an effective biomarker for early diagnosis of LUAD.

High expression of DARS2 indicates poor prognosis in lung adenocarcinoma.

BACKGROUND: DARS2 was overexpressed in multiple tumor types, but the biological role of DARS2 in lung adenocarcinoma (LUAD) have not been elucidated. METHODS: Firstly, the DARS2 expression in LUAD was explored using The Cancer Genome Atlas (TCGA). Then, qRT-PCR and Western blot were performed to confirm DARS2 expression in LUAD. Next, Cox regression and Kaplan-Meier methods were utilized to evaluate whether DARS2 expression can affect the overall survival. The relationships between DARS2 expression and clinicopathological characteristics were investigated by TCGA database. Moreover, we utilized Gene Set Enrichment Analysis (GSEA) to detect DARS2-related signaling pathways in LUAD. Finally, the special function of DARS2 in cell proliferation, invasion and apoptosis was assessed in vitro. RESULTS: The higher expression of DARS2 was found in LUAD compared to para-carcinoma tissues and significantly related to tumor stage, T stage, and M stage. The survival analysis indicated that DARS2 overexpression was related to poor prognosis in LUAD. Multivariate analysis suggested that DARS2 expression was a prognostic indicator. GSEA revealed that DARS2 was primarily involved in cell cycle-related pathways. In addition, upregulation of DARS2 facilitated LUAD cell proliferation, migration, invasion and inhabited apoptosis, DARS2 knockdown showed an opposite result. CONCLUSION: DARS2 modulates the proliferation, invasion and apoptosis of LUAD cells, and sever as a promising therapeutic target for LUAD.

[Velocity vector imaging assessment of early epirubicin-induced myocardial damage].

OBJECTIVE: To assess the left ventricular (LV) longitudinal systolic and diastolic function in patients treated by epirubicin by velocity vector imaging (VVI) and to discuss the important clinical value of VVI in quantitatively evaluating the regional longitudinal function. METHODS: Thirty patients with breast cancer treated with epirubicin chemotherapy and 30 normal controls were included in the study. Dynamic images of apical long axis, four-chamber and two chamber view were obtained in all subjects, and the longitudinal systolic and diatolic parameters were measured in all subjects, including systolic maximum velocity (Vs), systolic maximum strain (SS), systolic maximum strain rate (SSR), diastolic maximum velocity (Vd), and diastolic maximum strain rate (DSR). The parameters were compared between the 2 groups. The conventional echcardiographic parameters were also obtained. RESULTS: There was no significant change in all baseline parameters before the chemotherapy in 30 breast cancer patients compared with the normal controls (P>0.05). After the second chemotherapy cycle, DSR was lower in every segment, Vd was lower in the free wall, mainly the lateral, anterior and inferior wall (P<0.05), while Vd didn't change significantly in the septum wall (P>0.05). After the third chemotherapy cycle, Vd, DSR and SSR decreased significantly in all segments (P<0.05). Vs and SS didn't change significantly (P>0.05). CONCLUSION: VVI can monitor the epirubicin cardiotoxicity early and is more sensitive than echocardiograph.

Cancer/testis antigen HEMGN correlated with immune infiltration serves as a prognostic biomarker in lung adenocarcinoma.

HEMGN belongs to the Cancer/testis antigens (CTAs), which are expressed in various types of human cancers and have received particular attention in cancer immunotherapy. However, the potential function of HEMGN involved in lung cancer and the immune response is not yet elucidated. HEMGN expression in lung adenocarcinoma (LUAD) was estimated via the Tumor Immune Estimation Resource (TIMER), The Cancer Genome Atlas (TCGA), The University of Alabama at Birmingham Cancer data analysis Portal (UALCAN), and Human Protein Atlas databases. The prognostic role of HEMGN was investigated by Gene Expression Profiling Interactive Analysis (GEPIA), PrognoScan, and Kaplan-Meier plotter databases. The associations between HEMGN and clinicopathological parameters were analyzed with UALCAN database. Then, immunohistochemical and Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) analysis were performed to further verify the associations in tissue or serum samples. Serum from patients were detected for HEMGN antibody by enzyme-linked immunosorbent assay (ELISA). Flow cytometry was used to detect immune cell infiltration in peripheral blood of patients with LUAD. In addition, Gene Set Enrichment Analysis (GSEA) was conducted to investigate the functional role of HEMGN. Furthermore, we obtained the somatic mutation data from the TCGA LUAD dataset and analyzed the mutation profiles with "maftools" package. Finally, we evaluated the associations between HEMGN and immune infiltration level and the characteristic markers of immune cells in TIMER, GEPIA, and CIBERSORT. The mRNA and protein expressions of HEMGN were significantly decreased in LUAD patients. High HEMGN expression was remarkably associated with better prognosis in LUAD patients. The concentration levels of anti-HEMGN antibody in LUAD were significantly higher than that in healthy individuals and were closely correlated with clinical stage. In addition, HEMGN was involved in distinct typical genomic alterations in LUAD. GSEA demonstrated that HEMGN was significantly connected with immunity and substance metabolism. Notably, HEMGN was significantly related to immune infiltrates, including B cells, CD8 + T cells, CD4 + T cells, neutrophils, macrophages, dendritic cells (DCs), and various kinds of functional T cells. Furthermore, HEMGN had a significant association with diverse immune gene markers. HEMGN can be considered as a prognostic biomarker of LUAD and is associated with immune infiltration.

[Contrast-enhanced ultrasound in the diagnosis of benign and malignant hepatic tumors].

OBJECTIVE: To determine the value of contrast-enhanced ultrasound in the diagnosis of benign and malignant hepatic tumors. METHODS: A total of 83 patients with 123 focal liver lesions (FLLs) underwent contrast enhanced ultrasound (CEUS) examination. The contrast enhanced characterization of FLLs were compared. RESULTS: All the 103 lesions in hepatocallular carcinoma improved quickly in the arterial phase or portal phase. Altogether 98 lesions (95%) washed out during the late phase but the rest 5 lesions (5%) did not. Of the 69 lesions of hepatocellular carcinoma, 53(77%) enhanced global in the arterial phase or portal phase, and the rest 16 (23%) showed inhomogeneous enhancement but no enhancement in the central area during arterial phase or portal phase. A total of 66(96%) presented wash-out during the late phase, and 3(4%) had no wash-out. Of the 34 lesions of metastatic hepatic carcinoma, 24(71%)presented inhomogeneous enhancement in the arterial phase or portal phase, 10(29%) enhanced globally in the arterial phase or portal phase, 32 (94%) presented wash-out during the late phase, and 2(6%) had no wash-out in the late phase. Of the 20 lesions of benign hepatic tumor, 18(90%) presented inhomogeneous enhancement slowly in the arterial phase or portal phase, 14 (70%) slightly enhanced, and 20 (100%) presented no wash-out in the the late phase. CONCLUSION: CEUS can improve the accuracy of diagnosis of benign and malignant hepatic tumors.

Has_Circ_0002490 Circular RNA: A Potential Novel Biomarker for Lung Cancer.

Background: Lung cancer (LC) is ranked as a leading cause of cancer-related death worldwide. However, there are still few reliable screening biomarkers for daily clinical practice in LC. Circular RNAs (circRNAs) have been suggested as valuable diagnostic biomarkers in various cancers. In this study, the expression and diagnostic potential of several circRNAs for LC were explored. Methods: Seventy-two pairs of LC tissues and adjacent normal lung tissues were collected to measure the relative expression level of circRNAs using quantitative reverse transcription-polymerase chain reaction. In addition, the relationships between circRNAs and the clinicopathological features of LC patients were analyzed. Furthermore, the sensitivities and specificities of the circRNAs were evaluated by receiver operating characteristic (ROC) analysis. Results: The expression levels of has_circ_0002490, has_circ_0087357, has_circ_0004891, has_circ_0074368, and has_circ_0000896 were downregulated in LC tissues compared with adjacent normal lung tissues. The lower levels of has_circ_0002490, has_circ_0087357, has_circ_0004891, and has_circ_0000896 were significantly correlated with advanced disease stages. The area under the ROC curves of has_circ_0002490, has_circ_0087357, has_circ_0074368, has_circ_0004891, and has_circ_0000896 were 0.833, 0.793, 0.773, 0.730, and 0.645, respectively. Conclusions: Has_circ_0002490, has_circ_0087357, has_circ_0074368, has_circ_0004891, and has_circ_0000896 are capable of distinguishing LC tissues from normal lung tissues. Besides, the biggest area under the ROC curve value of has_circ_000249 suggests it appears to be a better diagnosis marker for LC patients.

Overexpression of SFXN1 indicates poor prognosis and promotes tumor progression in lung adenocarcinoma.

Sideroflexin 1 (SFXN1) functions as a mitochondrial serine transporter in one-carbon metabolism. The association between SFXN1 and tumorigenesis remains to be elucidated. This study illustrated the functional role of SFXN1 in lung adenocarcinoma (LUAD). SFXN1 expression in LUAD specimens was examined using western blotting and quantitative real-time PCR (qRT-PCR), and the prognostic value between SFXN1 and clinicopathological parameters was investigated. Subsequently, the effects of SFXN1 on cellular proliferation, migration, and apoptosis were assessed by using Transwell assays and flow cytometry in A549 and H1299 cell lines. Western blotting was also employed to explore the mechanism of tumor progression. SFXN1 was significantly elevated in the LUAD samples compared with the para-carcinoma tissues. Furthermore, SFXN1 expression was an independent prognostic predictor for patients with LUAD. The expression of SFXN1 was altered in A549 and H1299 cell lines and this showed that SFXN1 promoted cell proliferation, migration, and invasion and inhibited apoptosis. SFXN1, at least partially, influenced LUAD progression via the mTOR signaling pathway. Collectively, the findings from this study demonstrated that SFXN1 promotes LUAD progression via the mTOR pathway and that SFXN1 expression is associated with clinicopathological features of LUAD. SFXN1 significantly contributes to the development of LUAD and might have potential, not only as an independent prognostic marker of LAUD but also as a promising target for LUAD therapy.

Differences of Serum 25- (OH) D3 Level and Adverse Pregnancy Outcomes between Women with Gestational Diabetes and Healthy Pregnant Women.

BACKGROUND: The difference in serum 25-hydroxyvitamin D3 (25-(OH) D3 ) level between the gestational diabetes mellitus (GDM) and healthy pregnant women was analyzed, to provide the experimental evidence for the vitamin supplement in pregnant women, especially those with GDM. METHODS: Pregnant women (n=50) who received prenatal care in the Obstetrical Clinic of Xuzhou Maternity and Child Health Care Hospital in summer and winter of 2016 were enrolled. They were assigned to the summer GDM group, winter GDM group, summer control group and winter control group. The level of serum 25-(OH)D3 was determined using immunochromatography. RESULTS: The mean level of serum 25-(OH)D3 in pregnant women of four groups was lower than normal level. Compared with control group in corresponding season, the winter and summer GDM groups had significantly lower level of 25-(OH)D3 than the winter and summer control groups (P<0.05). The winter GDM group had significantly lower level of 25-(OH)D3 than the summer GDM group (P<0.05). The winter control group had significantly lower level of 25-(OH)D3 than the summer control group (P<0.05). The percentage of deficient 25-(OH)D3 level was the highest in winter GDM group. Vitamin D deficiency was severer in pregnant women with GDM than healthy pregnant women. In winter, vitamin D deficiency was severer than that in summer. CONCLUSION: Pregnant women, especially those with GDM, should pay more attention to vitamin D supplementation.