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Sperm-associated antigen 6 (SPAG6) is a newly identified cancer-testis antigen that has been revealed to contribute to the occurrence and development of various types of human cancer, such as ovarian, bladder, breast and lung cancer. However, to the best of our knowledge, the expression levels of SPAG6 in breakpoint cluster region (BCR)/ABL1-negative myeloproliferative neoplasms (MPNs) have not been investigated previously. Using reverse transcription-quantitative PCR and different tissue staining techniques, the present study revealed that SPAG6 was expressed by MPN cells, both at the mRNA and protein levels, and that nucleated erythroid precursors and megakaryocytes expressed the highest levels of SPAG6. In addition, SPAG6, which is known as a microtubule-associated protein, was found to exhibit nucleic, cytoplasmic or both cytoplasmic and nucleic subcellular localization patterns within the same patient or cell type; however, it did not always co-localize with β-tubulin. Furthermore, SPAG6 expression was revealed to be associated with fewer splenomegaly [P=0.015 for polycythemia vera (PV) and essential thrombocythemia (ET); and P=0.012 for primary myelofibrosis (PMF)] and myelofibrosis events (P=0.014 for PV and ET; and P=0.004 for PMF). In patients with PMF, upregulated expression levels of SPAG6 were also found to be associated with lower white blood cell counts (P=0.042) and lactate dehydrogenase levels (P=0.012), and higher hemoglobin levels (P=0.031) and platelet counts (P=0.025). In addition, the receiver operating characteristic curve analysis indicated that SPAG6 may be a potential biomarker for distinguishing MPN cases from healthy individuals. In conclusion, to the best of our knowledge, the present study is the first to report that aberrant SPAG6 expression may affect the disease phenotype and serve as a tumor biomarker in BCR/ABL1-negative MPNs.

CD47 functions as a dominant anti-engulfment signal on tumour cells and is overexpressed in various malignant tumours. However, the expression and functional significance of CD47 in triple-negative breast cancer (TNBC) is not completely understood. In the present study, CD47 was demonstrated to be overexpressed in TNBC solid tumours. Moreover, increased CD47 expression was significantly associated with an advanced tumour-node-metastasis stage, lymph node involvement and recurrence. Moreover, CD47 was an unfavourable and independent prognostic factor for 5-year disease-free survival in patients with TNBC. In addition, the expression of CD47 was associated with several markers of epithelial-mesenchymal transition (EMT). The present study was the first to demonstrate an association between increased expression of CD47 with EMT and poor prognosis of TNBC. Thus, CD47 may be a potential prognostic biomarker and therapeutic target for TNBC.

The present study investigated the mechanism of selective killing of liver cancer cells of melanoma differentiation associated gene-7 (MDA-7, also called IL-24α) in order to provide a theoretical basis for gene therapy of liver cancer. A recombinant eukaryotic expression vector (pcDNA3-MDA-7) containing human MDA-7 gene was constructed, which was then delivered to liver cancer cell line HepG2 and normal liver cell line L02. The positive cell clone was screened by G418. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was performed to confirm the occurrence of MDA-7 transcription in the transfected cells. The protein expression of MDA-7 was determined by western blot analysis. The effects of MDA-7 on liver cancer cell proliferation and apoptosis were investigated through MTT assay and flow cytometry by Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) double-staining. The mitochondrial protein was extracted from the normal liver cell line L02 and liver cancer cell line HepG2 at 3 day post-culture, in which the alterations of anti-apoptotic B-cell lymphoma-2 (Bcl-2), pro-apoptotic Bcl-2 associated X protein (Bax), mitochondria-released cytochrome c and caspase 9 were determined by western blot analysis. pcDNA3-MDA-7 mediated the expression of foreign gene MDA-7 in HepG2 and L02 cells. MDA-7 promoted liver cancer cell apoptosis and inhibited cell proliferation; while no effect was exerted on normal liver cells, as determined by the MTT assay and flow cytometry. Relative to the L02 cells, the protein expression of Bcl-2 was downregulated in the HepG2 cells, while that of Bax, cytochrome c and caspase 9 were upregulated. In the study, the eukaryotic expression vector pcDNA3-MDA-7 was successfully constructed, it can mediate the expression of MDA-7 in human liver cancer cells and normal liver cells and inhibits the proliferation of human liver cancer cells through the restored expression of mitochondrial pro-apoptotic Bcl-2.

Myosin heavy chain 11 (MYH11), encoded by the MYH11 gene, is a protein that participates in muscle contraction through the hydrolysis of adenosine triphosphate. Although previous studies have demonstrated that MYH11 gene expression levels are downregulated in several types of cancer, its expression levels have rarely been investigated in lung cancer. The present study aimed to explore the clinical significance and prognostic value of MYH11 expression levels in lung cancer and to further study the underlying molecular mechanisms of the function of this gene. The Oncomine database showed that the MYH11 expression levels were decreased in lung cancer compared with those noted in the normal lung tissue (P

Immunotherapy is effective in improving the survival and prognosis of patients with non-small cell lung cancer (NSCLC), and identifying effective immunomarkers is important for immunotherapy. Interleukin (IL)-36γ is a novel immunomarker that has an important function in the antitumor immune response. The present study investigated the association between IL-36γ and NSCLC to provide novel insight into immunotherapy for patients with NSCLC. Tissue microarrays of lung adenocarcinoma and squamous cell carcinoma were purchased for immunohistochemical analysis of IL-36γ expression levels and clinical parameters. In addition, fresh clinical NSCLC and adjacent normal tissue samples were collected to analyze IL-36γ mRNA expression levels using quantitative PCR. IL-36γ protein was primarily located in the cytoplasm, with a small quantity in the nucleus, and IL-36γ mRNA and protein expression levels in lung cancer tissues were significantly higher compared with those in adjacent normal tissues. Elevated IL-36γ protein expression levels were significantly associated with a higher tumor grade of lung adenocarcinoma; however, IL-36γ mRNA expression levels were inversely associated with the clinical Tumor-Node-Metastasis stage in patients with lung squamous cell carcinoma. In addition, patients with adenocarcinoma with high IL-36γ protein expression levels tended to longer post-operative survival times. These findings indicate that IL-36γ may have potential as an immunomarker for prediction of tumor progression and survival in patients with NSCLC.

The aim of the present study was to examine and discuss the association between multidrug resistance 1 gene (MDR1) of gastrointestinal tumors, the expression of P-glycoprotein and resistance to chemotherapeutic drugs. In this study, 126 cases of patients with gastrointestinal tumors admitted to hospital from February 2013 to February 2015 were selected. The expression levels of MDR1 gene were obsreved in the control population and patients before and after treatment by fluoresecent quantitative PCR. The protein expression level of P-glycoprotein was determined using western blotting and enzyme-linked immunosorbent assay. In addition, drug resistance was assessed by ATP-TCA chemosensitivity experiments. The results showed that before treatment, the expression of mRNA in MDR1 of tissues of gastrointestinal tract of the 126 cases was 108-fold larger than that of the gastrointestinal tract of the controls (p

Cancer metastasis remains responsible for the vast majority of cases of cancer-related morbidity and mortality. Metastasis, by its definition, is the spread of cancer from the primary site to the distant tissues. Advancing the scientific and clinical understanding of cancer metastasis is a high priority. The prerequisite requirement for pathological consistency may be compromised during metastasis. The present study reports the case of a cancer patient with different pathological types. The patient presented with pain in the neck and right hip, as well as weight loss. He underwent whole-body positron emission tomography-computed tomography, which identified a mass in the lung and abnormal metabolism of the bone. Biopsies of the ilium and lung were performed and he was shown to have lung adenocarcinoma and bone squamous carcinoma. The morphology and immunohistochemical patterns were completely different, while each lesion harbored an identical genetic profile. The bone lesion was identified to be a metastasis from the lung cancer. The patient was prescribed an epithelial growth factor receptor inhibitor, which resulted in a partial response in the lung mass and alleviation of the patient's bone pain. Through this case study, we advocate the importance of using genetic testing in addition to pathological assessment.

Sesquiterpenoids are a major type of compound found in Solanum lyratum (S. lyratum). The present study aimed to investigate whether sesquiterpenoids from S. lyratum demonstrated cytotoxicity against the MCF-7, HCT-8, A-549, SGC-7901 and BEL-7402 cell lines, and the mechanism of solajiangxin H and lyratol D, which exhibited high cytotoxicity against SGC-7901 cells (half maximal inhibitory concentration, IC50=4.8 and 5.9 µg/ml), was associated with mitochondria-mediated apoptosis. The results of the Cell Counting Kit-8 assay indicated that 15 sesquiterpenoids had cytotoxicity against the aforementioned cultured cells. The results of DAPI staining and western blot analysis, used to study the anticancer mechanisms of solajiangxin H and lyratol D in SGC-7901 cells, suggested that solajiangxin H and lyratol D induced the apoptosis of SGC-7901 cells significantly (P

Myosin heavy chain 11 (MYH11), encoded by the MYH11 gene, is a protein that participates in muscle contraction through the hydrolysis of adenosine triphosphate. Although previous studies have demonstrated that MYH11 gene expression levels are downregulated in several types of cancer, its expression levels have rarely been investigated in lung cancer. The present study aimed to explore the clinical significance and prognostic value of MYH11 expression levels in lung cancer and to further study the underlying molecular mechanisms of the function of this gene. The Oncomine database showed that the MYH11 expression levels were decreased in lung cancer compared with those noted in the normal lung tissue (P

Leukemia stem cells (LSCs) are responsible for therapeutic failure and relapse of acute lymphoblastic leukemia. As a result of the interplay between LSCs and bone marrow mesenchymal stem cells (BM-MSCs), cancer cells may escape from chemotherapy and immune surveillance, thereby promoting leukemia progress and relapse. The present study identified that the crosstalk between LSCs and BM-MSCs may contribute to changes of immune phenotypes and expression of hematopoietic factors in BM-MSCs. Furthermore, Illumina Genome Analyzer/Hiseq 2000 identified 7 differentially expressed genes between BM-MSCs(LSC) and BM-MSCs. The Illumina sequencing results were further validated by reverse transcription-quantitative polymerase chain reaction. Following LSC simulation, 2 genes were significantly upregulated, whereas the remaining 2 genes were significantly downregulated in MSCs. The most remarkable changes were identified in the expression levels of lumican (LUM) gene. These results were confirmed by western blot analysis. In addition, decreased LUM expression led to decreased apoptosis, and promoted chemoresistance to VP-16 in Nalm-6 cells. These results suggest that downregulation of LUM expression in BM-MSCs contribute to the anti-apoptotic properties and resistance to chemotherapy in LSCs.

Non-small cell lung cancer (NSCLC) is one of leading causes of cancer-associated mortality, with a high number of cases caused by metastasis. The early diagnosis of cancer contributes to the successful treatment of patients with lung cancer. The aim of the present study was to analyze the efficacy of marker gene detection and computed tomography (CT) in diagnosing human lung cancer. Lung cancer marker genes, including carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), tissue polypeptide antigen (TPA), pro-gastrin-releasing peptide (ProGRB), cytokeratin fragment 21-1 (Cyfra21-1) and neuron-specific enolase (NSE), were analyzed in patients with lung cancer. The tumor size was evaluated using CT, and the association between lung serum levels of marker gene protein expression and tumor size was investigated. A total of 328 patients with lung cancer were identified, including 204 adenocarcinoma, 75 large cell carcinoma and 49 squamous cell carcinoma cases. All patients were indicated to have a high serum level of CEA, CA125, TPA, ProGRB, Cyfra21-1 and NSE, compared with the normal range. Immunohistochemistry demonstrated higher expression levels of CEA, CA125, TPA, ProGRB, Cyfra21-1 and NSE in lung tumor tissues, compared with the normal range. Results indicated that CT was able to diagnose tumor size for patients with lung cancer. The CEA and CA125 expression levels were associated with CT-diagnosed adenocarcinoma tumor size. Large cell carcinoma tumor size was associated with serum levels of CEA, TPA and ProGRB. Results indicated that Cyfra21-1 and NSE were associated with the squamous cell carcinoma cases, as demonstrated using CT. In conclusion, these results indicated that comprehensive analysis of marker gene detection and CT results may be used to diagnose human lung cancer.

Pemetrexed is a candidate chemotherapy regimen for anthracycline- and taxane-pretreated advanced breast cancer. However, to the best of our knowledge, no efficient treatment efficacy biomarkers have been identified. In the present study, the potential correlation between thymidylate synthase (TYMS) expression and clinical response to pemetrexed was examined in advanced breast cancer. A retrospective collection was performed by using 77 advanced breast cancer subjects, who received at least three cycles of pemetrexed treatment in the Second Hospital of Shandong University hospital. TYMS expression was detected using immunohistopathological staining. The correlations between TYMS and therapeutic efficacies of different chemotherapy treatment were analyzed. The objective response rate (ORR) and disease control was 31.17 and 64.94%, respectively. Immunohistochemical staining demonstrated that TYMS expression was observed in the cytoplasm and nuclei of breast cancer cells. High TYMS expression was observed in 32 specimens. Elevated TYMS expression was correlated with higher histological grade and lymph node metastasis (P

Guan Chang Fu Fang (GCFF) is a natural compound, which is extracted from three medicinal plants, Agrimonia pilosa Ledeb., Patrinia scabiosaefolia and Solanum nigrum L. GCFF has demonstrated clinical efficacy in the treatment of colon cancer. At present, 5-fluorouracil (5-FU) is the primary active chemotherapeutic agent used for treating colon cancer. Using median-effect and apoptosis analyses, fluorescence microscopy and western blotting, the present study analyzed the association between GCFF and 5-FU in the human colon adenocarcinoma LoVo cell line. The effect of GCFF on the expression of chemotherapeutic agent-associated genes was also investigated. The results of the synergistic analysis revealed that GCFF exhibited a significant effect upon 5-FU-associated cytotoxicity within the LoVo cell line. This effect was observed over a broad dose-inhibition range (5–95%), but was particularly significant in the lower concentrations. The flow cytometry results revealed that low doses of GCFF or 5-FU induced S-phase arrest, as did a low-dose combination of the two drugs. After 48 h, GCFF significantly suppressed the expression levels of the chemotherapeutic agent resistance-associated genes within the colon cancer cells. The western blot analysis revealed that the combined effects of 5-FU and GCFF were due to a regulation of the B-cell lymphoma-2 family of proteins. The findings of the present study suggested that GCFF, when combined with 5-FU, has the potential to be a novel, chemotherapeutic compound for the treatment of colon cancer.

Colorectal cancer is one of the most common malignant tumors, and is associated with significant morbidity and mortality. In this study, recombinant analgesic-antitumor peptide (rAGAP), a protein consisting of small ubiquitin-related modifier (SUMO) linked with a hexa-histidine tag, was used as an antitumor analgesic peptide. The purpose of the present study was to investigate the antitumor activity of rAGAP in human colon adenocarcinoma SW480 cells and its potential molecular mechanisms of action. In this study, cell viability and apoptosis of rAGAP-treated SW480 cells was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry and 4′,6-diamidino-2-phenylindole (DAPI) staining. Western blotting was used to investigate the effects of rAGAP on p27, Bcl-2/Bax and PTEN/PI3K/Akt cellular signal transduction. Our results showed that rAGAP not only enhanced apoptosis, but also inhibited the proliferation of SW480 cells. rAGAP upregulates the expression of p27 in SW480 cells and leads to cell cycle arrest in the G1 phase. Furthermore, rAGAP significantly increases the production of Bax and PTEN and suppresses the activation of Bcl-2, phosphatidylinositol 3-kinase (PI3K) and phospho-Akt (p-Akt) in SW480 cells. These results suggest that rAGAP may be a potential new anti-colorectal cancer drug.

The present study aimed to investigate the molecular mechanisms and effect of Beclin-1 on autophagy, proliferation and apoptosis in the colorectal cancer (CRC) HCT116 and SW620 cells. Beclin-1 was silenced by RNA interference (RNAi) in HTC116 and SW620 cells. Reverse transcription-polymerase chain reaction and western blot were used to measure the expression of Beclin-1. The percentage of apoptotic cells was analyzed by cell counting kit-8 (CCK-8) and flow cytometry (FCM). Cell cycle and cell proliferation were analyzed by FCM and the MTT assay. The present study created 3 groups in the two cell lines, consisting of the targeting siRNA (TS) group, in which Beclin-1 was partially silenced, non-specific siRNA (NS) group and control group (CG; without transfection). By siRNA transfection, the mRNA and protein level of Beclin-1 in the TS group were significantly inhibited compared with the NS group and CG (P

Few cases of testicular metastases from prostate carcinoma have been reported, and asymptomatic metastases of prostate carcinoma to both the testis and epididymis are extremely rare. The current study presents the case of a 69-year-old male with testicular and epididymal metastases from prostate carcinoma. The patient was admitted to The First Hospital of Shijiazhuang with a 2-year history of lower urinary tract symptoms. Digital rectal examination revealed an enlarged multinodular prostate, and the serum prostate-specific antigen (PSA) level was >100 ng/ml. Magnetic resonance imaging showed prostate carcinoma with seminal vesicle involvement. A prostate biopsy showed prostate gland adenocarcinoma. The Gleason score was 3+3. The immunohistochemistry results were as follows: Prostatic acid phosphatase (+++), PSA (+++), P504s (+++), p63 (-) and cytokeratin 34βE12 (-), with a Ki-67 of ~5%. The patient was treated with a bilateral orchiectomy. The testicular pathology showed that the right testis and epididymis were invaded with metastatic adenocarcinoma. The left testis and epididymis were normal. The patient was treated with conventional flutamide endocrine therapy. At present the patient remains in a stable condition after 24 months of follow-up.

Cholangiocarcinoma is one of the most aggressive types of malignancy, and is associated with poor patient prognosis. Recent findings suggest that a decrease in pleckstrin homology-like domain family A, member 1 (PHLDA1) expression is significant in the induction of cell migration and tumor invasion. The clinicopathological significance of the expression of PHLDA1, and its potential correlation with the expression of CD133 in cholangiocarcinoma have remained to be elucidated. In the present study, PHLDA1 protein expression was investigated by immunohistochemical analysis of 218 cholangiocarcinoma tissue samples, as well as 30 para-neoplastic and 20 normal bile ducts. The expression status of PHLDA1 and CD133 was determined, and these results were analyzed against the age, gender, tumor location and size, histological grade, clinical stage and overall mean survival time of the patients. The expression of PHLDA1 protein was markedly decreased in 35.3% of cholangiocarcinomas, compared with that of the para-neoplastic and normal cholangiocytes. Carcinomas with loss of expression of PHLDA1 were significantly correlated with the tumor site (P=0.001), histological grade (P=0.020) and clinical stage (P=0.0001), but not with age (P=0.085), gender (P=0.456) or size (P=0.413), respectively. Kaplan-Meier survival analysis indicated that the loss of expression of PHLDA1 was significantly correlated with the overall survival time (Log rank=193.861; P=0.0001). Furthermore, the expression of PHLDA1 was found to be inversely correlated with the expression of CD133 (γ=-0.142; P=0.036). These findings suggested that the decreased expression of PHLDA1 may be significant in the carcinogenesis and progression of cholangiocarcinoma, and may represent a novel adjunct marker of disease prognosis.

Mediator Complex Subunit 12 (MED12) is a subunit of the mediator complex, which is believed to regulate global, as well as gene-specific, transcription. It has been reported that MED12 is mutated at high frequency in hysteromyoma. Recent studies have also shown that MED12 presents with different mutation frequencies in hysteromyoma patients of different populations. However, there are few studies with regard to the MED12 gene mutation in hysteromyoma patients in the Chinese Han population. In the present study, the MED12 mutations of 171 patients with hysteromyoma were analyzed; the results showed that 93 patients exhibited different MED12 mutations, including 131G→T, 131G→A, 130G→A, 146C→T, 130G→A, 130G→C, 128A→C, 130G→T, 127Ins27, 118_132Del15, 117_134Del18, 131_148Del18 and 141_165Del15. The mutation frequency was similar to that found in individuals of African descent or individuals of other non-Caucasian ethnicities, and lower than that in the Finnish or North American populations. Further analysis of 141 patients whose hysteromyoma was measured showed that the mutation frequency of MED12 in patients with large hysteromyomas was significantly lower than that in those with small hysteromyomas. These results suggested that MED12 mutation was important in the development of hysteromyomas in the Chinese Han population and that the size of the hysteromyoma may negatively correlate with the mutation frequency of MED12. This study supplemented current information on MED12 mutations in different races and may aid in developing personalized diagnoses for patients with hysteromyoma in the future.