Cytoplasmic Expression of the EGFL6 Protein Is an Independent Prognostic Factor for Shortened Patient Survival in Human Hepatocellular Carcinoma.

BACKGROUND/AIM: Hepatocellular carcinoma (HCC) is the most common primary liver tumor and the second leading cause of cancer-related deaths worldwide. The current study aimed to investigate the clinical relevance of the epidermal growth factor-like domain multiple 6 (EGFL6) expression in HCC and to evaluate whether the expression of EGFL6 in HCC has diagnostic and prognostic significance. PATIENTS AND METHODS: This study aimed to investigate EGFL6 protein expression levels in 260 HCC tissue specimens using immunohistochemical analyses. The immunohistochemical study demonstrated strong EGFL6 expression in the cytoplasm of non-tumor or normal hepatocytes. RESULTS: The findings revealed that 98 patients exhibited low EGFL6 expression, while 162 patients displayed high EGFL6 expression. We explored the associations between cytoplasmic EGFL6 expression and the clinicopathological features of HCC. Decreased cytoplasmic EGFL6 expression exhibited significant correlations with worse cellular differentiation, higher T classification, vascular invasion, higher stage, and tumor recurrence. Survival analyses, using Kaplan-Meier survival curves for HCC patients, revealed that those with reduced cytoplasmic EGFL6 expression experienced significantly worse disease-free survival (DFS) and disease-specific survival (DSS). Univariate and multivariate analyses identified EGFL6 as an independent predictor for decreased expression, differentiation grade, vascular invasion, stage, or recurrence in cases of DFS or DSS in HCC. CONCLUSION: This study represents, to the best of our knowledge, the first investigation into the expression of EGFL6 protein in HCC. Taken together, our findings strongly suggest that EGFL6 likely plays a crucial role in the pathogenesis of HCC and indicates that targeting EGFL6 could be a promising therapeutic strategy.

Correlation Between Low Cytoplasmic Expression of XBP1 and the Likelihood of Surviving Hepatocellular Carcinoma.

BACKGROUND/AIM: Our objectives in this study were to (i) evaluate the clinical significance of X-box-binding protein 1 (XBP1) expression in cases of hepatocellular carcinoma (HCC) and (ii) assess the potential of XBP1 to be used as a prognostic biomarker. PATIENTS AND METHODS: The expression of XBP1 protein in 267 HCC tissue specimens was measured using immunohistochemistry in order to characterize the associations among XBP1 expression, clinicopathological factors and survival outcomes. Survival analysis using follow-up data was used to assess the prognostic value of XBP1 in cases of HCC. Immunohistochemistry revealed a significant decrease in cytoplasmic XBP1 protein expression in HCC tumor tissue. RESULTS: Immunoreactivity results showed that low cytoplasmic XBP1 expression was significantly associated with vascular invasion, as well as poor 5-year overall survival and long-term disease-specific (DSS) and disease-free (DFS) survival rates. Kaplan-Meier survival curves further confirmed a significant association between low cytoplasmic XBP1 protein expression and poor DSS and DFS. Univariate and multivariate analyses revealed that XBP1 expression, tumor differentiation, vascular invasion, tumor stage, and the rate of recurrence were linked to DSS, while low cytoplasmic XBP1 expression remained an independent predictor of poor DSS. Our analysis also revealed that XBP1 expression, tumor differentiation, vascular invasion, and T classification were linked to DFS, while low cytoplasmic XBP1 expression remained an independent predictor of poor DFS. CONCLUSION: Low cytoplasmic XBP1 protein expression may play an important role in the pathogenesis of HCC, which suggests that XBP1 could potentially be targeted to benefit therapeutic strategies for HCC.

Biological and clinical significance of the AGE-RAGE axis in the aggressiveness and prognosis of prostate cancer.

Dietary factors and chronic hyperglycemia are linked to the formation of advanced glycation end products (AGEs) and prostate cancer (PCa) risk. The activation of the receptor for AGEs (RAGE) acts as a bridge between various RAGE ligands and certain malignancies. This study showed that the interaction of AGEs and RAGE promoted PCa cell proliferation, invasion, and autophagy-mediated survival in response to chemotherapeutic agents. RAGE-overexpressed PCa cells underwent epithelial-mesenchymal transition and showed increased cancer stem cell-like properties. In mouse xenograft models, RAGE-overexpressed cells showed more substantial tumorigenic capacity than parental cells, whereas RAGE knockdown decreased tumorigenicity. The clinical data validated a positive correlation between high AGE and RAGE expressions with poor clinical outcomes. Our findings suggest that the AGE-RAGE axis facilitates PCa progression and aggressiveness. Prostatic AGEs and RAGE expression levels are associated with PCa prognosis. Adherence to a reduced-AGE diet and targeting RAGE are potential approaches to complement and synergize with the current PCa therapies.

Quantitative and amplification-free detection of SOCS-1 CpG methylation percentage analyses in gastric cancer by fiber optic nanoplasmonic biosensor.

A new innovative approach is essential for early and effective diagnosis of gastric cancer, using promoter hypermethylation of the tumor suppressor, SOCS-1, that is frequently inactivated in human cancers. We have developed an amplification-free fiber optic nanoplasmonic biosensor for detecting DNA methylation of the SOCS-1 human genome. The method is based on the fiber optic nanogold-linked sorbent assay of PCR-free DNA from human gastric tumor tissue and cell lines. We designed a specific DNA probe fabricated on the fiber core surface while the other probe is bioconjugated with gold nanoparticles in free form to allow percentage determination and differentiating the methylated and unmethylated cell lines, further demonstrating the SOCS-1 methylation occurs in cancer patients but not in normal cell lines. The observed detection limit is 0.81 fM for methylated DNA, and the detection time is within 15 min. In addition, our data were significantly correlated to the data obtained from PCR-based pyrosequencing, and yet with superior accuracy. Hence our results provide new insight to the quantitative evaluation of methylation status of the human genome and can act as an alternative to PCR with a great potential.

KLF10 Functions as an Independent Prognosis Factor for Gastric Cancer.

Background and Objectives: Kruppel-like factor 10 (KLF10) participates in the tumorigenesis of several human cancers by binding to the GC-rich region within the promoter regions of specific genes. KLF10 is downregulated in human cancers. However, the role of KLF10 in gastric cancer formation remains unclear. Materials and Methods: In this study, we performed immunohistochemical staining for KLF10 expression in 121 gastric cancer sections. Results: The loss of KLF10 expression was correlated with advanced stages and T status. Kaplan-Meier analysis revealed that patients with higher KLF10 levels had longer overall survival than those with lower KLF10 levels. Univariate analysis revealed that in patients with gastric cancer, advanced stages and low KLF10 levels were associated with survival. Multivariate analysis indicated that age, gender, advanced stages, and KLF10 expression were independent prognostic factors of the survival of patients with gastric cancer. After adjusting for age, gender, and stage, KLF10 expression was also found to be an independent prognostic factor in the survival of patients with gastric cancer. Conclusion: Our results collectively suggested that KLF10 may play a critical role in gastric cancer formation and is an independent prognosis factor of gastric cancer.

Cytoplasmic phosphorylated ERK1/2 expression in patients with melanoma is associated with tumor stage and metastasis.

Melanoma is the cause of most deaths from skin cancer. The extracellular signal-regulated kinase 1/2 (ERK1/2) pathway has been reported to participate in progression of melanoma in fair skinned populations. ERK1/2 is found in both the cytoplasm and nucleus of cells, and phosphorylated ERK1/2 has been implicated in tumor progression. We investigated the relation between melanoma progression and expression of cytoplasmic and nuclear phosphorylated ERK1/2. We examined 34 surgically resected melanomas and investigated their clinicopathologic characteristics. We found immunostaining of phosphorylated ERK1/2 in all melanomas and faint staining in benign nevi. We found expression of cytoplasmic phosphorylated ERK1/2 in most melanomas; however, nuclear phosphorylated ERK1/2 expression was found in only five melanomas. Expression of cytoplasmic phosphorylated ERK1/2 was related to the tumor stage in melanoma. Nine of 10 cases of distant metastasis were positive for cytoplasmic phosphorylated ERK1/2. Our findings suggest that phosphorylated ERK1/2 expression is relevant to clinical pathology and that in melanoma patients, phosphorylated ERK1/2 expression is found in both the cytoplasm and nucleus. Our findings suggest that cytoplasmic phosphorylated ERK1/2 participates in progression of melanoma and that it could be a useful target for clinical treatment of melanoma.

Reduction in and Preventive Effects for Oral-Cancer Risk with Antidepressant Treatment.

Areca nut (AN) was identified as carcinogenic to humans. Around 600 million people globally use AN in some form, yet no effective therapeutic drug is available to overcome AN addiction. This preclinical study examines the effects of antidepressants on AN use with animal models. We produced AN powder and dissolved it into drinking water, training 55 C57BL/6 mice in free self-selection to drink AN water or normal water. Then, the mice were randomly divided into four groups. Selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), and tricyclic antidepressants (TCAs) were given as three treatment groups and one placebo group for four weeks. In the follow-up period, the preference and amount of free selection of AN and normal water, and oral pathological change were evaluated. There was a significant decrease in preference for AN drinking during the first four weeks, and the 36th week after drug withdrawal in the MAOI and SSRI groups (all p < 0.05). The drug-reducing effect of AN water in the 1-4-week period was significant in the MAOI group (p < 0.0001) and was also significant in the 3-4-week period in the SSRI group (p = 0.03). The TCA group did not show a decrease effect. At the endpoint (60 weeks), oral mucosal fibrosis (OSF) levels and risk in the SSRI (p = 0.0081) and MAOI (p = 0.01) groups were significantly lower than those in the control group. Antidepressant drugs MAOIs and SSRIs could reduce the amount of AN use and decrease the early stage of oral fibrosis in mice, but SSRIs may need to be boosted again.

Methylomic analysis identifies C11orf87 as a novel epigenetic biomarker for GI cancers.

Gastric cancer is one of the leading causes of cancer death worldwide. Previous studies demonstrated that activation of STAT3 is crucial for the development and progression of gastric cancer. However, the role of STAT3 in neuronal related gene methylation in gastric cancer has never been explored. In this study, by using DNA methylation microarray, we identified a potential STAT3 target, C11orf87, showing promoter hypomethylation in gastric cancer patients with lower STAT3 activation and AGS gastric cancer cell lines depleted with STAT3 activation. Although C11orf87 methylation is independent of its expression, ectopic expression of a constitutive activated STAT3 mutant upregulated its expression in gastric cancer cell line. Further bisulfite pyrosequencing demonstrated a progressive increase in DNA methylation of this target in patient tissues from gastritis, intestinal metaplasia, to gastric cancer. Intriguingly, patients with higher C11orf87 methylation was associated with better survival. Furthermore, hypermethylation of C11orf87 was also frequently observed in other GI cancers, as compared to their adjacent normal tissues. These results suggested that C11orf87 methylation may serve as a biomarker for diagnosis and prognosis of GI cancers, including gastric cancer. We further postulated that constitutive activation of STAT3 might be able to epigenetically silence C11orf87 as a possible negative feedback mechanism to protect the cells from the overactivation of STAT3. Targeted inhibition of STAT3 may not be appropriate in gastric cancer patients with promoter hypermethylation of C11orf87.

Arecoline N-oxide initiates oral carcinogenesis and arecoline N-oxide mercapturic acid attenuates the cancer risk.

Arecoline N-oxide (ANO), an oxidative metabolite of the areca nut, is a predictable initiator in carcinogenesis. The mechanisms of arecoline metabolites in human cancer specimens is still limited. This present study aims to estimate the oral squamous cell carcinoma (OSCC) inductive activity between arecoline metabolites in human cancer specimens/OSCC cells. We have collected 22 pairs (tumor and non-tumor part) of patient's specimens and checked for clinical characteristics. The identification of arecoline and its metabolites levels by using LC-MS/MS. The NOD/SCID mice model was used to check the OSCC inductive activity. The tumor part of OSCC samples exhibited higher levels of arecoline and ANO. Besides, ANO treated mice accelerates the NOTCH1, IL-17a and IL-1ß expressions compared to the control mice. ANO exhibited higher cytotoxicity, intracellular ROS levels and decline in antioxidant enzyme levels in OC-3 cells. The protein expression of NOTCH1 and proliferation marker levels are significantly lower in NOM treated cells. Overall, ANO induced initial stage carcinogenesis in the oral cavity via inflammation, ROS and depletion of antioxidant enzymes. Arecoline N-oxide mercapturic acid (NOM) attenuates the initiation of oral carcinogenesis.

Association between EGFR Gene Mutation and Antioxidant Gene Polymorphism of Non-Small-Cell Lung Cancer.

EGFR mutation status is considered as an important predictor of therapeutic responsiveness in non-small-cell lung carcinoma patients. Recent evidence suggests that antioxidant gene polymorphisms are potential predictors of lung cancer risk. Thus, stratification of EGFR mutation-related phenotypes by antioxidant gene polymorphism status can be an effective approach in terms of improving the prognosis of lung cancer patients. The present study was designed to evaluate the distribution frequency of antioxidant gene polymorphisms in lung adenocarcinoma, as well as its association with hotspot EGFR mutations. The study findings revealed that a statistically significant association exists between EGFR L858R mutation and AG + GG genotypes of SOD rs4880 polymorphism. Furthermore, the subgroup analysis data revealed that compared to AA genotype of SOD rs4880, AG + GG genotypes were significantly associated with advanced cancer stage and distant metastasis. Taken together, these findings can be utilized clinically to predict cancer aggressiveness, metastatic, potential and therapeutic responsiveness of lung cancer patients.

Prognostic and Clinical Implications of WNK Lysine Deficient Protein Kinase 1 Expression in Patients With Hepatocellular Carcinoma.

BACKGROUND/AIM: Hepatocellular carcinoma (HCC) is a particularly malignant form of cancer prevalent throughout the world; however, there is a pressing need for HCC biomarkers to facilitate prognosis and risk assessment. PATIENTS AND METHODS: This paper reports on the potential prognostic value of WNK lysine deficient protein kinase 1 (WNK1) in cases of HCC. We analyzed the expression of WNK1 at the mRNA level using omics data from the UALCAN database. We then verified our findings through the immunohistochemical (IHC) staining of various human cancer tissue as well as 59 HCC samples paired with corresponding normal tissues. The prognostic value of mRNA or protein expression by WNK1 was evaluated using the Kaplan-Meier method. RESULTS: Initial screening results revealed significantly higher WNK1 expression levels in HCC tissue compared to normal tissue. Verification using the paired HCC samples confirmed that the expression of WNK1 was indeed significantly higher in HCC tissue samples than in adjacent normal tissues. High WNK1 expression levels were significantly correlated with clinicopathological variables, including gender and histologic grade. Kaplan-Meier survival analysis revealed that high WNK1 expression levels were associated with poor HCC prognosis. Finally, univariate and multivariate analysis identified WNK1 as a prognostic factor for TNM stage in cases of HCC. CONCLUSION: In summary, WNK1 is overexpressed at the mRNA and protein levels, and correlated with poor prognosis. Thus, WNK1 expression could potentially be used as a biomarker in HCC prognosis.

Cytoplasmic CK1ε Protein Expression Is Correlated With Distant Metastasis and Survival in Patients With Melanoma.

BACKGROUND/AIM: Casein kinase 1 epsilon (CK1ε) is a member of the casein kinase 1 family, which includes highly conserved and ubiquitous serine/threonine protein kinases. Recent research has revealed that CK1ε plays an important role in a variety of human cancer types; however, its role in human melanoma remains unclear. The aim of this study was to elucidate the clinical role of CK1ε in patients with melanoma. PATIENTS AND METHODS: Samples from 34 patients with melanoma were analyzed by immunohistochemical staining. Formalin-fixed paraffin-embedded tissue microarrays were also examined by two histopathologists to assess CK1ε protein expression in humans. RESULTS: Cytoplasmic CK1ε protein expression was significantly lower in tumor tissue than in normal tissue. Lack of cytoplasmic CK1ε protein was significantly correlated with distant metastasis (p=0.022) and poorer survival (p=0.030). However, Kaplan-Meier survival analysis revealed that elevated expression of cytoplasmic CK1ε protein was not significantly associated with the overall survival of patients with melanoma. Univariate and multivariate analyses demonstrated that lack of cytoplasmic CK1ε protein expression was related to distant metastasis (p<0.001 and p=0.004), showing that CK1ε was a prognostic factor. CONCLUSION: CK1ε protein expression might serve as a prognostic indicator in the treatment of patients with melanoma.

Decreased Cytoplasmic Expression of ADAMTS14 Is Correlated with Reduced Survival Rates in Oral Squamous Cell Carcinoma Patients.

A disintegrin and metalloproteinase with thrombospondin motif 14 (ADAMTS14) is a member of the zinc-dependent protease family that is implicated in the occurrence and progression of tumors. Oral cancer (OC) is a common cancer worldwide, but it is particularly prevalent in Taiwan. However, whether the expression of ADAMTS14 is correlated with the carcinogenesis and progression of oral squamous cell carcinoma (OSCC) has not yet been investigated. In this study, we used immunohistochemistry (IHC) to examine 250 OSCC specimens in order to identify correlations between the cytoplasmic expression of ADAMTS14 and (1) clinicopathological features of OSCC as well as (2) clinical outcomes of OSCC. Our results indicate that cytoplasmic expression of ADAMTS14 was lower in OSCC tissues than in normal tissues. In analyzing correlations between ADAMTS14 expression and clinicopathological features, we found that negative cytoplasmic expression of ADAMTS14 was significantly associated with higher frequencies of lymph node metastasis and more advanced AJCC stages (III/IV). Kaplan-Meier survival analysis revealed that negative cytoplasmic expression of ADAMTS14 was also associated with significantly worse OSCC survival. Univariate and multivariate analyses confirmed that cytoplasmic expression of ADAMTS14 was associated with lymph node metastasis, tumor stage, and tumor grade and also indicated that cytoplasmic ADAMTS14 expression may be an independent prognostic factor for OSCC. This is the first study to report that the cytoplasmic expression level of ADAMTS14 is associated with OSCC prognosis and tumor progression. Our data indicate that ADAMTS14 can serve as a prognostic marker and a potential therapeutic target for OSCC.

Metformin Mitigates Nickel-Elicited Angiopoietin-Like Protein 4 Expression via HIF-1α for Lung Tumorigenesis.

Nickel (Ni), which is a carcinogenic workplace hazard, increases the risk of lung cancer. Angiopoietin-like protein 4 (ANGPTL4) is a multifunctional cytokine that is involved in both angiogenesis and metastasis, but its role in lung cancer is still not clear. In this study, we assessed the role of ANGPTL4 in lung carcinogenesis under nickel exposure and investigated the effects of the antidiabetic drug metformin on ANGPTL4 expression and lung cancer chemoprevention. Our results showed that ANGPTL4 is increased in NiCl2-treated lung cells in a dose- and time-course manner. The expression of ANGPTL4 and HIF-1α induced by NiCl2 were significantly repressed after metformin treatment. The downregulation of HIF-1α expression by ROS savenger and HIF-1α inhibitor or knockdown by lentiviral shRNA infection diminished NiCl2-activated ANGPTL4 expression. Chromatin immunoprecipitation and the luciferase assay revealed that NiCl2-induced HIF-1α hypoxia response element interactions activate ANGPTL4 expression, which is then inhibited by metformin. In conclusion, the increased presence of ANGPTL4 due to HIF-1α accumulation that is caused by nickel in lung cells may be one mechanism by which nickel exposure contributes to lung cancer progression. Additionally, metformin has the ability to prevent NiCl2-induced ANGPTL4 through inhibiting HIF-1α expression and its binding activity. These results provide evidence that metformin in oncology therapeutics could be a beneficial chemopreventive agent.

Impact of Polymorphisms in Casein Kinase 1 Epsilon and Environmental Factors in Oral Cancer Susceptibility.

In Taiwan, the incidence rate of oral cancer is constantly increasing. Polymorphisms and lifestyle habits are major contributing factors to the development of oral cancer in such cases. Casein kinase 1 epsilon (CK1ε) gene expression plays a role in numerous cancers, and the knockdown of CK1ε induces tumor cell-selective cytotoxicity. The present study was designed to determine the effects of CK1ε gene polymorphisms combined with environmental carcinogens on susceptibility to developing oral squamous cell carcinoma and its clinicopathological status. Four single-nucleotide polymorphisms (SNPs) in CK1ε gene (rs135745, rs135764, rs1997644 and rs2075984) from 741 oral cancer patients and 462 healthy controls were analyzed using real-time polymerase chain reaction. Our results shown that variant types (GC) of CK1ε polymorphic rs135745 exhibited a significantly higher risk of 1.41 (95% confidence interval [CI]: 1.036-1.919) for oral cancer than did wild type alleles. Furthermore, these CK1ε gene SNPs along with betel-quid chewing and/or tobacco use further increased susceptibility to oral cancer. Moreover, variant genotypes (GC+CC) of CK1ε rs135745 were significantly associated with lymph node metastasis. These results suggested that the CK1ε gene polymorphism is associated with the clinicopathological development of oral cancer and increases individuals' susceptibility to environmental carcinogens (e.g., smoking and betel-quid chewing) in terms of developing oral cancer.

ALPK1 regulates streptozotocin-induced nephropathy through CCL2 and CCL5 expressions.

ALPK1 is associated with chronic kidney disease, gout and type 2 diabetes mellitus. Raised renal ALPK1 level in patients with diabetes was reported. Accelerated fibrotic nephropathies were observed in hyperglycaemic mice with up-regulated ALPK1. The aim of this study was to identify the mediators contributing to ALPK1 effect involving in nephropathies induction. The haematoxylin and eosin staining, Masson's trichrome and immunohistochemical analysis of ALPK1, NFkB, CCL2 and CCL5 were performed in the mice kidney. Cytokine antibody array analysis was performed in streptozotocin-treated wild-type mice (WT-STZ) and streptozotocin-treated ALPK1 transgenic mice (TG-STZ). The ALPK1 levels were measured in mice kidney and in cultured cells. We found that the higher levels of renal CCL2/MCP-1, CCL5/Rantes and G-CSF expression in TG-STZ compared with the WT-STZ. Glucose increased ALPK1 expressions in monocytic THP1 and human kidney-2 cells. The protein expression of ALPK1, NFkB and lectin was up-regulated in glucose-treated HK-2 cells. Knockdown of ALPK1 reduced CCL2 and CCL5 mRNA levels, whereas overexpressed ALPK1 increased CCL2 and CCL5 in cultured kidney cells. Taken together, these results show that high glucose increases ALPK1 and chemokine levels in the kidney. Elevated ALPK1 expression enhances renal CCL2 and CCL5 expressions in vivo and in vitro. ALPK1 is a mediator for CCL2 and CCL5 chemokine up-regulation involving in diabetic nephropathies induction.

Complete non-puerperal uterine inversion caused by uterine hemangioma: A case report.

OBJECTIVE: Uterine inversion is a rare postpartum complication. Non-puerperal uterine inversion is extremely rare. It mostly occurs with uterine tumors, especially leiomyoma. In most instances, the inversion may not be noticed until the time of surgery. The preoperative diagnosis is difficult. CASE REPORT: We report a case of non-puerperal complete uterine inversion that was initially diagnosed as cervical cancer. The uterine inversion was diagnosed preoperatively and she underwent total abdominal hysterectomy and bilateral salpingooophorectomy. The histological examination showed uterine hemangioma. CONCLUSION: Accurate diagnosis of the non-puerperal uterine inversion is important. Surgical intervention is necessary and it provides good prognosis. Hemangioma may be one of the causes of non-puerperal uterine inversion.

UNC13C Suppress Tumor Progression via Inhibiting EMT Pathway and Improves Survival in Oral Squamous Cell Carcinoma.

Potential function of UNC13C in variety of cancers including, oral squamous cell carcinoma (OSCC) remains obscure. In the present study, immunohistochemical staining in tissue microarrays containing 268 OSCC samples showed that UNC13C protein levels were inversely correlated with AJCC Stage III and IV (P = 0.002) and death (P = 0.0134). Patients with lower UNC13C expression had a significantly shorter survival (P = 0.0231) than those with higher UNC13C expression. We also identified decreased overall UNC13C expression in oral cancer cell lines. In addition, our functional analysis of UNC13C shows that overexpression of UNC13C inhibited migration and invasion capacities of SCC-9 and SAS cells compared with the empty plasmid transfected cells. Further experiments suggested that transcription factors (Slug, Snail, Twist, and ZEB1) and mesenchymal marker (Vimentin) were down regulated and Tight Junction Protein (Claudin1) was up regulated after UNC13C overexpression in SCC9 and SAS cells. The novel role of UNC13C is revealed for the first time in OSCC. In summary, these results suggest that UNC13C as a novel tumor suppressor and an essential regulator of EMT signaling pathway during OSCC progression, and thus it could be used as a target for preventing oral cancer metastasis.

c-MYC expression in T (III/IV) stage oral squamous cell carcinoma (OSCC) patients.

Purpose: c-MYC has been noted in many tumor types, but its functional significance and clinical utility in oral squamous cell carcinoma (OSCC) are not well known. Here we studied the expression of c-MYC in correlation to clinical outcome in patients with oral squamous cell carcinoma. Methods: The current study, using immunohistochemical staining, first examined c-MYC expression in OSCC patients and further correlated its expression with clinicopathological parameters. Results: c-MYC was expressed in the majority of OSCC patients (n=133). The c-MYC expression is associated with histological grade (P=0.0205) of patients with oral squamous cell carcinoma. Multivariate Cox regression analysis revealed that TN stage (P<0.001), American Joint Committee on Cancer (AJCC) stage (P<0.0001), and tumor differentiation (P=0.0025) were independent factors for overall survival in patients with OSCC except for c-MYC expression (P>0.05). Multiplicative-scale interaction between T stage (III/IV) and low c-MYC expression on mortality risk was identified (P=0.0233). Kaplan-Meier survival analysis demonstrated that oral cancer patients (T III/IV stage) with high c-MYC expression had better survival than those with low and medium c-MYC expression (P=0.0270). Conclusion: Our data indicate that c-MYC is a potential biomarker that can be used as a therapeutic target for treating OSCC patients with T stage (III/IV).