Expression Of Transgelin-2 Research Articles

Transgelin-2, a novel cancer stem cell-related biomarker, is a diagnostic and therapeutic target for biliary tract cancer.

Biliary tract cancer (BTC) is a relatively rare but aggressive gastrointestinal cancer with a high mortality rate. Cancer stem cell (CSC) populations play crucial roles in tumor biology and are responsible for the low response to anti-cancer treatment and the high recurrence rate. This study investigated the role of Transgelin-2 (TAGLN2), overexpressed in CSC in BTC cells, and analyzed its expression in patient tissues and serum to identify potential new targets for BTC. TAGLN2 expression was suppressed by small-interfering or short hairpin RNAs, and its effects on tumor biology were assessed in several BTC cell lines. Furthermore, the effects of TAGLN2 silencing on gemcitabine-resistant BTC cells, differentially expressed genes, proteins, and sensitivity to therapeutics or radiation were assessed. TAGLN2 expression was also assessed using western blotting and immunohistochemistry in samples obtained from patients with BTC to validate its clinical application. Suppression of TAGLN2 in BTC cell lines decreased cell proliferation, migration, invasion, and tumor size, in addition to a reduction in CSC features, including clonogenicity, radioresistance, and chemoresistance. TAGLN2 was highly expressed in BTC tissues, especially in cancer-associated fibroblasts in the stroma. Patients with a low stromal immunohistochemical index had prolonged disease-free survival compared to those with a high stromal immunohistochemical index (11.5 vs. 7.4 months, P = 0.013). TAGLN2 expression was higher in the plasma of patients with BTC than that in those with benign diseases. TAGLN2 had a higher area under the curve (0.901) than CA19-9, a validated tumor biomarker (0.799; P < 0.001). TAGLN2 plays a critical role in promoting BTC cell growth and motility and is involved in regulating BTC stemness. Silencing TAGLN2 expression enhanced cell sensitivity to radiation and chemotherapeutic drugs. The expression of TAGLN2 in patient tissue and plasma suggests its potential to serve as a secretory biomarker for BTC. Overall, targeting TAGLN2 could be an appropriate therapeutic strategy against advanced cancer following chemotherapy failure.

Hypoxia-Inducible Transgelin-2 Confers Treatment Resistance through Activation of PI3K/Akt/GSK3β Pathway in Glioblastoma

Glioblastoma (GBM) patients with wild-type IDH experience worse survival response to the standard treatment of surgery followed by radiation therapy (RT) and temozolomide (TMZ) chemotherapy compared to their mutant IDH counterparts. This treatment has remained relatively ineffective partly due to the highly invasive phenotype of GBM leading to therapeutic resistance and tumor recurrence. Hypoxia is one of the key characteristic features of GBM which results in cancer metastasis and confers treatment resistance. Therefore, it is paramount to identify targets to help overcome hypoxia-induced treatment resistance in glioblastoma. Our lab has identified transgelin-2 (TAGLN2) to be significantly upregulated in IDH-wt GBM through multiple molecular profiling studies. This study aims to understand the mechanisms by which TAGLN2 confers treatment resistance for developing additional treatments for GBM. Additionally, active drug development efforts are also underway to target TAGLN2 for circumventing these therapeutic resistance mechanisms for effective GBM therapy. RNAi-mediated TAGLN2 knockdown (KD) approach was employed to assess the functions of TAGLN2 in GBM patient-derived xenograft (PDX) cell lines. Series of in vitro functional assays were performed to assess the role of TAGLN2 in these cell lines. Cell proliferation, invasion ± RT and/or TMZ were assessed by MTS and Trans-well invasion assays. Subsequently, WB analysis of oncogenic signaling pathways was performed following Transgelin-2 KD. Co-IP assays and Biacore/SPR analyses were performed to study the binding affinity and kinetics for the interaction of PTEN with TAGLN2. Further, cells were intracranially implanted in nude mice to assess the role of TAGLN2 on tumor growth in vivo. Conditional KD of TAGLN2 reduces cell proliferation, survival and invasive potential of GBM PDX cell lines. TAGLN2 KD also improved the sensitivity of these cells to both TMZ and radiation in vitro, as assessed by proliferation, survival, clonal expansion, and invasion. Histopathological studies of human GBM tumors and mouse xenograft tumors showed elevated expression of TAGLN2 in the peri-necrotic region of the tumors indicating that TAGLN2 protein level was upregulated by hypoxia. We also show that TAGLN2 is induced in hypoxic microenvironments with GBM PDX cell lines and its overexpression may enhance cellular resistance towards conventional therapy. Subsequently, we also show that hypoxia-induced TAGLN2 activates the PI3K/Akt oncogenic pathway through binding and inhibition of PTEN. Finally, in vivo data using an orthotopic xenograft mouse model shows reduction of tumor growth with knockdown of TAGLN2. Our in vitro and in vivo xenograft studies suggest that TAGLN2 confers treatment resistance to GBM contributing to tumor recurrence. Altogether, TAGLN2 may serve as a potential therapeutically vulnerable target in GBM specifically through its role in cell survival and invasion.

TAGLN2 Promotes the Proliferation, Migration, Invasion, and EMT of Clear Cell Renal Cell Carcinoma Through the PI3K/Akt Signaling Pathway.

The effect of Transgelin 2 (TAGLN2) on clear cell renal cell carcinoma (ccRCC) is unknown. Thisstudy explored the potential role and mechanism of ccRCC. The expression of TAGLN2 in Pan-cancers was analyzed using the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases. TCGA-KIRC database was used to analyze subsequent prognostic survival, pathway enrichment, and immune infiltration. Relevant experimental methods could explain the effect of TAGLN2 expression on tumor cell proliferation, migration, invasion, and apoptosis. Apoptosis, proliferation, Epithelial-to-Mesenchymal Transition (EMT), and PI3K/AKT signaling pathway-related protein expression were determined through western blotting. In the TCGA + GTEx database, mRNA-TAGLN2 expression was clearly increased in pan-cancer tissues, and the same result was found in ccRCC patients based on KIRC analysis results. In addition, TAGLN2 was associated with poor clinical stage, pathological grade, and survival prognosis. TAGLN2 is highly expressed in ccRCC tissues and in vitro TAGLN2 silencing of cells inhibits the proliferation, migration, invasion, and EMT of ccRCC cancer cells. Furthermore, TAGLN2-related differential genes enriched in the PI3K/AKT signaling pathway were negatively regulated after TAGLN2 silencing. Moreover, TAGLN2 may promote tumor immune escape and increase the risk of distant metastasis in immune infiltration-related analyses. TAGLN2 can be used as a single indicator to explain the survival probability of patients with ccRCC. In vitro TAGLN2 silencing inhibited the malignant properties of ccRCC by blocking the PI3K/AKT signaling pathway. In addition, TAGLN2 contributes to tumor immune escape and may be a potential therapeutic target for ccRCC.

Transgelin-2 Involves in the Apoptosis of Colorectal Cancer Cells Induced by Tanshinone-IIA.

Tanshinone IIA (TanIIA) is the main active ingredient in the fat-soluble components isolated from Salvia miltiorrhiza Bunge. Our previous studies have convincingly proved that TanIIA is an effective drug against human colorectal carcinoma cells. In order to further demonstrate the effect of TanIIA on CRC, we carried out exploratory research about it in vivo and in vitro. The results demonstrated that TanIIA were observably more effective than control group in preventing tumor growth, and it has increased the survival time. Cancer cells viability and proliferation were accompanied by concentration and time dependent decline reached with TanIIA. We found that TanIIA altered the morphology of cytoskeleton and it could obviously induce apoptosis of colorectal cancer cells and block the cells in the G0/G1 phase. TanIIA also increased phosphorylation of p38MAPK, upregulated ATF-2 expression and downregulated Transgelin-2 expression, which could be reversed by SB203580, a p38MAPK-specific inhibitor. Our results suggested that TanIIA could induce apoptosis of colorectal cancer and block the cells in G0/G1 phase involved in downregulating the expression of Transgelin-2 through p38MAPK signal pathway.

TAGLN2-Regulated Trophoblast Migration, Invasion and Fusion are Impaired in Preeclampsia.

Preeclampsia (PE) is a serious disease during pregnancy that affects approximately eight million mothers and infants worldwide each year and is closely related to abnormal trophoblast function. However, research on placental trophoblast functional abnormalities is insufficient, and the etiology of PE is unclear. Here, we report that the expression of transgelin-2 (TAGLN2) was downregulated in the placenta of patients with PE. In addition, a lack of TAGLN2 significantly reduced the ability of trophoblasts to migrate, invade and fuse. A co-immunoprecipitation (Co-IP) and microscale thermophoresis analysis showed that TAGLN2 bound directly to E-cadherin. A decrease in TAGLN2 expression led to a reduction in cleavage of the E-cadherin extracellular domain, thereby regulating the function of trophoblasts. In addition, we found that a reduction in soluble E-cadherin may also have an effect on blood vessel formation in the placenta, which is necessary for normal placental development. What’s more, the in vivo mouse model provided additional evidence of TAGLN2 involvement in the development of PE. By injecting pregnant mice with Ad-TAGLN2, we successfully generated a human PE-like syndrome that resulted in high blood pressure and some adverse pregnancy outcomes. Overall, the association between TAGLN2 and PE gives a new insight into PE diagnosis and treatment.

Transgelin-2 interacts with CD44 to regulate Notch1 signaling pathway and participates in colorectal cancer proliferation and migration.

The abnormal expression of transgelin-2 (TAGLN2) is related to tumor occurrence and progression. However, the underlying molecular mechanism of TAGLN2 in human colorectal cancer (CRC) is still poorly understood. Compared with adjacent tissues, TAGLN2 is overexpressed in CRC tissues. Its expression level is negatively correlated with the overall survival rate of patients with CRC. In addition, knockdown of TAGLN2 inhibited the proliferation and invasion of CRC cells. We also showed that TAGLN2 could interact with CD44 to regulate the Notch-1 signaling pathway. Our findings indicate there is increased TAGLN2 expression in CRC and that it may serve as a promising potential therapeutic target for CRC.

Retracted Article: Overexpression of circ_0034642 contributes to hypoxia-induced glycolysis, cell proliferation, migration and invasion in gliomas by facilitating TAGLN2 expression via sponging miR-625-5p.

Glioma is an aggressive brain cancer with poor prognosis and high invasiveness. Dysregulation of circular RNAs (circRNAs) has been widely discovered in various cancers, including glioma. However, the molecular mechanism of circ_0034642 in glioma is still unclear. The expression of circ_0034642, microRNA (miR)-625-5p and transgelin-2 (TAGLN2) in glioma tumors and cells was detected by performing a quantitative real-time polymerase chain reaction (qRT-PCR). The stability of circ_0034642 was determined by carrying out RNase R treatment. Cell proliferation was evaluated by performing the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Glycolysis was analyzed by measuring the extracellular acidification rate (ECAR) using glucose detection and lactic acid detection kits. Cell migration and invasion were determined by performing the transwell assay. Protein expression levels of the proteins hexokinase 2 (HK2), matrix metalloproteinase-2 (MMP2), matrix metalloproteinase-9 (MMP9) and TAGLN2 were analyzed using western blots. The interaction between miR-625-5p and circ_0034642 or TAGLN2 was proved using a dual-luciferase reporter system. Animal models were established by subcutaneously injecting glioma cells stably transfected with sh-NC or sh-circ_0034642. Circ_0034642 and TAGLN2 were overexpressed whereas miR-625-5p was expressed at low levels in glioma tumors and cells. Moreover, circ_0034642 and TAGLN2 were upregulated while miR-625-5p was downregulated under hypoxic conditions in a time-dependent manner. Next, elimination of circ_0034642 was shown to inhibit cell glycolysis, proliferation, migration and invasion under hypoxic conditions in gliomas. Then, we found that circ_0034642 acted as a “sponge” of miR-625-5p while TAGLN2 acted as a target of miR-625-5p. In addition, recovery of circ_0034642 attenuated the repression mediated by miR-625-5p on glioma cell glycolysis and progression under hypoxic conditions. Meanwhile, an inhibitor of miR-625-5p alleviated TAGLN2 deficiency-induced inhibition of glioma cell development under hypoxic conditions. We also discovered that circ_0034642 could interact with miR-625-5p and further alter the expression of TAGLN2. Lastly, a circ_0034642 knockdown hindered tumor growth in vivo by regulating the miR-625-5p/TAGLN2 axis. Enhanced expression of circ_0034642 was found to promote cell glycolysis, proliferation, migration and invasion under hypoxic conditions in gliomas by sponging miR-625-5p to improve TAGLN2 expression, providing prospective biomarkers for the diagnosis of glioma.

Downregulation of transgelin 2 promotes breast cancer metastasis by activating the reactive oxygen species/nuclear factor‑κB signaling pathway.

Transgelin 2 (TAGLN2) is a cytoskeletal protein of the calponin family. Abnormal expression of TAGLN2 was observed in various types of cancer. Our previous study reported that TAGLN2 expression was reduced in lymph node-positive breast cancer patients; however, the role of TAGLN2 in breast cancer metastasis remains unknown. In the present study, the role of TAGLN2 in breast cancer metastasis was investigated in vitro and in vivo via Transwell migration, luciferase and flow cytometry assays, and a mouse xenograft model. Proteins interacting with TAGLN2 were identified via co-immunoprecipitation assays and liquid chromatography/mass spectrometry, and the signaling pathway associated with the effects of TAGLN2 was investigated. Additionally, western blotting and reverse transcription-quantitative polymerase chain reaction were performed to further explore the potential pathway in which TAGLN2 may be involved and the mechanism underlying its effects in breast cancer metastasis. The present study reported that TAGLN2 expression was increased by 11.4-fold in patients without distant metastasis compared with those positive for distant metastasis. Knockdown of TAGLN2 resulted in increased cell migration in vitro and promoted lung metastasis in vivo. Additionally, overexpression of TAGLN2 suppressed lung metastasis in a mouse model. Peroxiredoxin 1 (PRDX1), an important reactive oxygen species (ROS) regulator, was revealed to interact with TAGLN2. In addition, mitochondrial redistribution and PRDX1 downregulation were reported following TAGLN2 silencing, which promoted ROS production and nuclear factor (NF)-κB activation in breast cancer cells. This induced the expression of metastasis-associated genes, including C-X-C chemokine receptor 4, matrix metalloproteinase (MMP)1 and MMP2. The present study proposed TAGLN2 to function as a tumor suppressor and that loss of TAGLN2 may promote the metastasis of breast cancer by activating the ROS/NF-κB signaling pathway.

Transgelin-2 expression in breast cancer and its relationships with clinicopathological features and patient outcome.

Transgelin-2 is an actin-binding protein that is widely expressed in various tissues and organs of the body, and reportedly may participate in the development and progression of multiple cancers. However, the clinical significance of transgelin-2 still remains controversial. We, therefore, aimed to determine the expression of transgelin-2 in breast cancer as well as its correlation with the tumorigenesis, progression and prognosis of human breast cancer. We collected tissues of 58 breast cancer patients from our hospital and 1090 samples from The Cancer Genome Atlas (TCGA) database. X-tile software was used to divide the transgelin-2 mRNA expression level in the database, logistic regression model was used to identify independent factors influencing transgelin-2 mRNA expression, and then Cox regression and Kaplan-Meier analysis were used to find factors that influence survival of breast cancer. Transgelin-2 was significantly overexpressed in breast cancer tissues from our hospital and receiver operating characteristic (ROC) curve indicated that transgelin-2 may have diagnostic value. Meanwhile, estrogen receptor (ER) was in inverse correlation with transgelin-2 protein and mRNA expression, and transgelin-2 expression was positively correlated with Ki67 in breast cancer tissues. Logistic regression model revealed that TNM stage, ER and progesterone receptor (PR) status were independent factors for transgelin-2 mRNA expression. Patients with high transgelin-2 mRNA expression showed a poor survival and the trend was statistically significant only in ER-negative patients. Transgelin-2 was expressed significantly higher in breast cancer cells and correlated with some clinicopathological factors. High transgelin-2 expression might predict poor prognosis for ER-negative patients.

Transgelin 2 overexpression inhibits cervical cancer cell invasion and migration.

Cervical cancer is a malignancy that threatens female health. The present study aimed to investigate the role of transgelin 2 (TAGLN2) in cervical cancer. Reverse transcription‑quantitative polymerase chain reaction and western blotting were conducted to detect the mRNA and protein expression levels of particular factors in HeLa cells. Cell Counting kit‑8, wound healing and Transwell assays were conducted to determine cell viability, and migratory and invasive abilities, respectively. The results demonstrated that the expression levels of TAGLN2 were decreased in cervical cancer tissues and were associated with the survival time of patients with cervical cancer. In addition, the expression of TAGLN2 was significantly reduced in three cervical cancer cell lines (HeLa, SiHa and C‑33A) compared with in a normal cervical cell line. The present study also demonstrated that TAGLN2 overexpression in HeLa cells could inhibit cell viability, migration and invasion, and it was suggested that this may occur via upregulation of the expression levels of E‑cadherin and inhibitor of nuclear factor κ‑light‑chain‑enhancer of activated B cells (NF‑κB) (IκB), and downregulation of C‑X‑C chemokine receptor type 4, matrix metalloproteinase (MMP)‑2, MMP‑9, p50 and transcription factor p65. In conclusion, TAGLN2 was revealed to inhibit cell viability, and the migratory and invasive abilities of HeLa cervical cancer cells via regulating the expression of metastasis‑associated factors and the NF‑κB signaling pathway. The present study proposed a novel target gene for the diagnosis, treatment and prognosis of cervical cancer.

Oncogenic transgelin-2 is differentially regulated in isocitrate dehydrogenase wild-type vs. mutant gliomas.

The presence of an isocitrate dehydrogenase (IDH1/2) mutation in gliomas is associated with favorable outcomes compared to gliomas without the mutation (IDH1/2 wild-type, WT). The underlying biological mechanisms accounting for improved clinical outcomes in IDH1/2 mutant gliomas remain poorly understood, but may, in part, be due to the glioma CpG island methylator phenotype (G-CIMP) and epigenetic silencing of genes. We performed profiling of IDH1/2 WT versus IDH1/2 mutant Grade II and III gliomas and identified transgelin-2 (TAGLN2), an oncogene and actin-polymerizing protein, to be expressed at significantly higher levels in IDH1/2 WT gliomas compared to IDH1/2 mutant gliomas. This differential expression of TAGLN2 was primarily due to promoter hypermethylation in IDH1/2 mutant gliomas, suggesting involvement of TAGLN2 in the G-CIMP. Our results also suggest that TAGLN2 may be involved in progression due to higher expression in glioblastomas compared to IDH1/2 WT gliomas of lower grades. Furthermore, our results suggest that TAGLN2 functions as an oncogene by contributing to proliferation and invasion when overexpressed in IDH1/2 WT glioma cells. Taken together, this study demonstrates a possible link between increased TAGLN2 expression, invasion and poor patient outcomes in IDH1/2 WT gliomas and identifies TAGLN2 as a potential novel therapeutic target for IDH1/2 WT gliomas.

MiR-145-5p inhibits the proliferation and migration of bladder cancer cells by targeting TAGLN2.

MicroRNA-145-5p (miR-145-5p) is found to be involved in tumor development and progression. However, there are few studies on the effects of miR-145-5p on bladder cancer (BC). The role of miR-145-5p in BC was predicted by analysis of cell proliferation and migration in this study. The miR-145-5p and transgelin-2 (TAGLN2) expressions were evaluated via reverse transcription-quantitative PCR (RT-qPCR) or western blot analysis. The MTT and Transwell assay assessed cell proliferation and migration. TAGLN2 targeted to miR-145-5p was determined using luciferase assays. The results showed that the miR-145-5p downregulation was found in BC. miR-145-5p overexpression inhibited cell proliferation and migration in BC. Moreover, miR-145-5p directly targeted TAGLN2, and TAGLN2 expression was increased in BC. In addition, the high expression of TAGLN2 promoted cell proliferation and migration in BC. miR-145-5p appeared to regulate TAGLN2 in BC, and it also inhibited the cell proliferation and migration. The novel miR-145-5p/TAGLN2 axis may provide new therapeutic implications for BC.

TAGLN2, a novel regulator involved in Hepatitis B virus transcription and replication

Hepatitis B virus (HBV) infection is one of the major health problems in the world. Transgelin-2 (TAGLN2) expression has been revealed to be significantly altered in previous studies concerning HBV-host interaction. The present study investigated TAGLN2 expression patterns in HBV related hepatocellular carcinoma (HCC) tissues and its role in HBV transcription and replication. We collected 59 HBV related HCC tissue samples, their adjacent non-tumoral tissues and 16 normal livers to make the tissue microarray. TAGLN2 protein was detected by immunohistochemistry and the transcriptional levels of TAGLN2, HBc, HBs and HBx were detected by qRT-PCR. Then we investigated the function of TAGLN2 on HBV transcription and replication in vitro by ectopic expressing or knocking down TAGLN2 in HepG2 and HepG2.2.15 cell lines. We further studied the effect of HBx on TAGLN2 expression with a Tet-on HBx expressing cell line. TAGLN2 protein expression was lower in normal livers and HBV-HCC tissues comparing to adjacent non-tumoral tissues. The transcriptional levels of TAGLN2 in HBV-HCC tissues and their adjacent tissues were positively related to that of HBc, HBs and HBx (P < 0.05). Ectopic expression of TAGLN2 in vitro could enhance HBV transcription and replication while suppressing TAGLN2 had the contrary effect. TAGLN2 could be induced by HBx in a dose-dependent manner. Our data demonstrated that TAGLN2 might be an HBx induced positive host factor involved in HBV transcription and replication and HBx related liver fibrosis and tumorigenesis.

Transgelin is upregulated in stromal cells of lymph node positive breast cancer

Transgelin and transgelin-2 have been discussed as potential markers of various cancers. Here we identified increased transgelin level in lymph node positive vs. negative, low grade primary breast cancer tissues using 2-DE in the cohort of 12 patients. We further clinically validated 2-DE results in an independent cohort of 48 low grade breast cancer patients through untargeted and targeted proteomics analysis (iTRAQ-2D-LC–MS/MS, mTRAQ-SRM), at transcript level and using immunohistochemistry. Another group of 48 high grade tumors of different breast cancer subtypes was analyzed together with the low grade samples to test transgelin specificity for low grade tumors and to study transgelin relation to known molecular markers and histological features. The results confirmed transgelin connection with the lymph node metastasis. As a marker of a reactive tumor stroma, transgelin can be connected with the higher risk of metastasis development. Moreover, we observed significant down-regulation of transgelin in high vs. low grade tumors caused by decreased content of stromal cells (mainly expressing transgelin) in high grade tumor tissue. We also analyzed expression of transgelin-2 in the second cohort using proteomics and immunohistochemistry. Transgelin-2 was mainly expressed by epithelial cancer cells and its levels were increased in metastatic and poorly differentiated tumors. Biological significanceBoth transgelin and transgelin-2 have been previously described as potential markers of many types of cancer. We are specifying this connection to metastatic affection of lymph nodes and cell differentiation in breast cancer. In the wider context, the results of our study highlight tumor stroma as a source of cancer biomarkers and point out how measured levels of tissue markers can actually reflect cellular feature of cancer mass.

Proteomic analysis of differential protein expression by brain metastases of gynecological malignancies

Brain metastases of gynecological malignancies are rare, but the incidence is increasing. Patients with brain metastases have a poor prognosis, therefore early detection and optimal management is necessary. In order to determine a new biomarker, we aimed to identify proteins that associated with brain metastases. We investigated proteins associated with brain metastases of gynecological malignancies in three patients who underwent surgical resection (stage IIb cervical cancer, stage Ib endometrial cancer, and stage IIIb ovarian cancer). Proteomic analysis was performed on formalin-fixed paraffin-embedded (FFPE) samples of the primary tumors and brain metastases, which were analyzed by liquid chromatography with tandem mass spectrometry. Thereafter, candidate proteins were identified by the Scaffold system and Mascot search program, and were analyzed using western blotting and immunohistochemistry. As a result, a total of 129 proteins were identified. In endometrial and ovarian cancers, western blotting revealed that the expression of alpha-enolase (ENO1) and triosephosphate isomerase (TPI-1) was higher and the expression of Transgelin-2 (TAGLN2) was lower in metastatic tumors than in primary tumors. On the other hand, the expression of TPI-1 and TAGLN2 was lower in metastatic tumors than in primary tumors in cervical cancer. Immunohistochemistry confirmed that ENO1 expression was elevated in the metastatic tumors compared with the primary tumors. In conclusion, the present study showed that FFPE tissue-based proteomics analysis can be powerful tool, and these findings suggested that ENO1, TPI-1, and TAGLN2 may have a role in the development and progression of brain metastasis from gynecological malignancies.

Clinical Significance of Pituitary Tumor Transforming Gene 1 and Transgelin-2 in Pancreatic Cancer

Human pituitary tumor transforming gene 1 (PTTG1) is an oncogenic transcription factor that is overexpressed in many malignancies, especially cancers with metastatic potential, while transgelin-2 (TAGLN2) is an actin-binding protein shown to be a tumor suppressor. However, the expression and clinical significance of PTTG1 and TAGLN2 in pancreatic cancer remain unclear. The present study aimed to investigate the expression and clinical significance of PTTG1 and TAGLN2 in human primary pancreatic cancer. Seventy-five cases of human pancreatic cancer tissues were collected. The expression of PTTG1 and TAGLN2 protein was assessed using immunohistochemistry (IHC) through tissue microarray procedure. The clinicopathologic characteristics of all patients were analyzed. As a result, the expression of PTTG1 and TAGLN2 in cancerous tissues showed the positive staining mainly in the cytoplasm, and they were found in cancerous tissues with higher strong reactivity rate compared with the adjacent non-cancer tissues (ANCT) (56.0 percent vs 22.7 percent, P less than 0.001; 100 percent vs 84 percent, P=0.002), elevating with the ascending order of tumor malignancy. Furthermore, the positive expression of PTTG1 was associated with the gender of pancreatic cancer patients, but did not correlate with their age, pathological styles, tumor size, tumor sites, TNM staging, perineural infiltration and distant metastasis (each P greater than 0.05). In addition, Spearman rank correlation analysis showed the positive correlation of PTTG1 with TAGLN2 (r=0.624, P less than 0.001). Taken together, PTTG1 and TAGLN2 are highly expressed in human pancreatic cancer, and the positive expression of PTTG1 is associated with the gender of cancer patients, suggesting that it may represent a potential therapeutic target for the treatment of pancreatic cancer.

Expression of transgelin-2 and clinical significance in colorectal cancer

To investigate the relationship between the expression of transgelin-2 and the clinicopathological factors of colorectal carcinoma and evaluate the value of transgelin-2 in prognostic assessment of the colorectal cancer patients. Using tissue microarray and immunohistochemical methods, we examined transgelin-2 of 120 colorectal cancer patients received surgical treatment from September 2002 to April 2004, including 74 male and 46 female, age from 26 to 89 years. Analyzed the relationship between transgelin-2 and both the clinicopathological features and prognosis of the colorectal cancer by using χ² test and Kaplan-Meier survival analysis. Cox proportion hazard regression analysis was used to study the independent prognostic factors. The positive rate of transgelin-2 expression was 69.2% in colorectal carcinoma. The transgelin-2 expression correlated with differentiation degree (χ² = 5.420), lymph nodes metastasis (χ² = 45.577), distant metastasis (χ² = 12.009), and TNM staging (χ² = 47.577). The survival time was (39 ± 5) months in patients with positive expression of the transgelin-2, while (59 ± 3) months in patients with negative expression. The patient's survival time was statistically correlated with the transgelin-2 expression (P = 0.003). Distant metastasis (RR = 8.318, 95%CI: 4.119 - 16.790), lymph nodes metastasis (RR = 2.794, 95%CI: 1.246 - 6.263) and transgelin-2 expression (RR = 1.834, 95%CI: 1.118- 2.973) were independent prognostic factors in patients with colorectal cancer (P < 0.05). The expression of transgelin-2 is correlated with clinicopathological features and prognosis in colorectal cancer, may be the potential marker of metastasis and the prognosis of colorectal cancer patients.