Preoperative Use and Discontinuation of Traditional Chinese Herbal Medicine and Dietary Supplements in Taiwan: A Cross-Sectional Questionnaire Survey.

Traditional Chinese herbal medicine has widespread use in Taiwan. This cross-sectional questionnaire survey investigates the preoperative use and discontinuation of Chinese herbal medicine and dietary supplements among Taiwanese patients. We obtained the types, frequency, and sources of Chinese herbal remedies and supplements used. Among 1428 presurgical patients, 727 (50.9%) and 977 (68.4%) reported the use of traditional Chinese herbal medicine and supplements in the past one month, respectively. Only 17.5% of the 727 patients stated discontinuation of herbal remedies 4.7 ± 5.1 (1-24) days before the surgery, and 36.2% took traditional Chinese herbal medicine with concomitant physician-prescribed Western medicine for their underlying diseases. The most commonly used Chinese herbs are goji berry (Lycium barbarum) (62.9%) and Si-Shen-Tang (48.1%) in single and compound forms, respectively. The presurgical use of traditional Chinese herbal medicine was common in patients undergoing gynecologic (68.6%) surgery or diagnosed with asthma (60.8%). Women and those with a high household income had a greater tendency to use herbal remedies. This study demonstrates the high proportion of the presurgical use of Chinese herbal remedies and supplements along with physician-prescribed Western medicine in Taiwan. Surgeons and anesthesiologists should be aware of the potential adverse effects of drug-herb interaction for Chinese patients.

Combined Evaluation of MAP1LC3B and SQSTM1 for Biological and Clinical Significance in Ductal Carcinoma of Breast Cancer.

Breast cancer is the leading cause of cancer death in women worldwide. The microtubule-associated protein light chain 3B (MAP1LC3B) and adaptor sequestosome 1 (SQSTM1) are two major markers for autophagy. Increased protein levels of MAP1LC3B and SQSTM1 are considered to be causes of autophagy inhibition or activation in various types of cancers. However, the roles of MAP1LC3B and SQSTM1 in breast cancer are still not clear. Using a tissue microarray from 274 breast invasive ductal carcinoma (IDC) patients, we found that tumor tissues showed higher protein levels of MAP1LC3B and cytoplasmic SQSTM1 in comparison to those in adjacent normal tissues. Moreover, high levels of MAP1LC3B were associated with better survival, including disease-specific survival and disease-free survival (DFS) in IDC patients. Furthermore, high co-expression of MAP1LC3B and SQSTM1 was significantly associated with better DFS in IDC patients. Astonishingly, the autophagy inhibitor accumulated the protein levels of MAP1LC3B/SQSTM1 and enhanced the cytotoxic effects of cisplatin and paclitaxel in MCF7 and BT474 breast cancer cell lines, implying that autophagy inhibition might result in poor prognosis and chemosensitivity in IDC. Taken together, high co-expression of MAP1LC3B and SQSTM1 might serve as a potential diagnostic and prognostic biomarker for IDC patients.

Effect of EGFR on SQSTM1 Expression in Malignancy and Tumor Progression of Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is one of the most common types of malignant tumor. Sequestosome 1 (SQSTM1) serves as an adaptor of autophagy for degrading protein aggregates. The regulation of autophagy by EGFR and its clinical impacts are indicated in various types of cancer. However, the association of EGFR and SQSTM1 in OSCC is still unknown. Our results show that the expression levels of SQSTM1 and EGFR proteins are higher in tumor tissues than in the corresponding tumor-adjacent (CTAN) tissues of OSCC patients. The expression levels of SQSTM1 were positively associated with the EGFR expression level. High co-expression of SQSTM1 and EGFR is associated with poor prognosis in OSCC patients. Moreover, SQSTM1 expression is decreased in EGFR-knockdown cells. Cell growth and invasion/migration are also decreased in cells with single/combined knockdowns of EGFR and SQSTM1 or in SQSTM1-knockdown cells without EGFR kinase inhibitor Lapatinib treatment compared to that in scrambled cells. However, cell growth and invasion/metastasis were not significantly different between the scrambled cells and SQSTM1-knockdown cells in the presence of Lapatinib. This study is the first to indicate the biological roles and clinical significance of SQSTM1 regulation by EGFR in OSCC.

Clinical Significance and the Role of Guanylate-Binding Protein 5 in Oral Squamous Cell Carcinoma.

Guanylate binding protein 5 (GBP5) is the interferon (IFN)-inducible subfamily of guanosine triphosphatases (GTPases) and is involved in pathogen defense. However, the role played by GBP5 in cancer development, especially in oral squamous cell carcinoma (OSCC), is still unknown. Herein, next-generation sequencing analysis showed that the gene expression levels of GBP5 were significantly higher in OSCC tissues compared with those found in corresponding tumor adjacent normal tissues (CTAN) from two pairs of OSCC patients. Higher gene expression levels of GBP5 were also found in tumor tissues of 23 buccal mucosal squamous cell carcinoma (BMSCC)/14 tongue squamous cell carcinoma (TSCC) patients and 30 oral cancer patients from The Cancer Genome Atlas (TCGA) database compared with those in CTAN tissues. Immunohistochemical results showed that protein expression levels of GBP5 were also higher in the tumor tissues of 353 OSCC patients including 117 BMSCC, 187 TSCC, and 49 lip squamous cell carcinoma patients. Moreover, TCGA database analysis indicated that high gene expression levels of GBP5 were associated with poor overall survival in oral cancer patients with moderate/poor cell differentiation, and associated with poor disease-free survival in oral cancer patients with moderate/poor cell differentiation and lymph node metastasis. Furthermore, GBP5-knockdowned cells exhibited decreased cell growth, arrest at G1 phase, and decreased invasion/migration. The gene expression of markers for epithelial-mesenchymal transition and cancer stemness was also reduced in GBP5-silenced oral cancer cells. Taken together, GBP5 might be a potential biomarker and therapeutic target for OSCC patients, especially for those with poor cell differentiation and lymph node metastasis.

Knowledge, attitude, and barriers regarding prescribing long-term opioids among Taiwan physicians treating officially registered patients with chronic noncancer pain.

BACKGROUND: Prescribing opioids for patients with chronic noncancer pain (CNCP) remains controversial. This study surveyed Taiwanese physicians who were clinically treating CNCP outpatients with long-term opioids. METHODS: Anonymous questionnaires investigating the clinical practices, opioid knowledge, attitude, and barriers regarding the prescription of long-term opioids were delivered to 66 physicians treating CNCP outpatients who were officially registered and monitored by the Taiwan Food and Drug Administration in 2011. RESULTS: All 66 (100%) physicians responded to the survey, comprising 41 (62%) board-certified pain specialists and 25 (38%) nonpain board-certified physicians. Pain specialists treated a greater number of CNCP outpatients and attended more CNCP training courses than nonpain board-certified physicians (97.6% vs. 56.0%, p < 0.001). Most of pain specialists stated that they were familiar with the Taiwan's narcotic regulations for CNCP patients (92.7% vs. 68.0%, p = 0.015). In addition, pain specialists were less likely to skip or reduce the dosage and duration of opioid prescriptions (22.0% vs. 36.0%, p < 0.001). By contrast, nonpain board-certified physicians had significantly less knowledge and a more negative attitude toward opioid prescription. The major perceived barriers were physician's reluctance to prescribe opioids (78% vs. 92%) and an inadequate knowledge of pain management (73% vs. 84%) among all physicians. CONCLUSION: Among the Taiwanese physicians treating the officially registered CNCP patients, nonpain board-certified physicians had fewer patients, less knowledge, and an increased negative attitude toward long-term opioid prescriptions. Better education on chronic pain management is needed for improvement of clinical practice.

UBE2C is a Potential Biomarker for Tumorigenesis and Prognosis in Tongue Squamous Cell Carcinoma.

Ubiquitin-conjugating enzyme 2C (UBE2C) involves in numerous cellular processes and the tumor progression in many cancers. However, its role in oral squamous cell carcinoma (OSCC) is unclear. We aimed to investigate the role and clinical significance of UBE2C in OSCC. The expression levels of UBE2C were examined by immunohistochemistry in 185 buccal mucosa squamous cell carcinomas, 247 tongue squamous cell carcinomas (TSCCs) and 75 lip squamous cell carcinomas. The roles of UBE2C in cell growth, invasion/migration and cancer stemness were also examined in OSCC cells. The expression levels of UBE2C protein were higher in tumor tissues than they were in the corresponding tumor adjacent normal tissues from OSCC patients. Higher UBE2C expression was associated with poor cell differentiation and lymph node invasion in OSCC patients. High UBE2C expression was also correlated with shorter disease-specific survival in TSCC patients having poor cell differentiation, advanced pathological stages, lymph node metastasis as well as receiving radiation therapy. Compared to control cells, OSCC cells in which UBE2C was silenced showed decreased cell proliferation, migration/invasion and colony formation and they exhibited lower expression levels of the following cancer stemness markers-ALDH1/A2, CD44, CD166 and EpCAM. High co-expression levels of UBE2C/CD44, UBE2C/CD166 and UBE2C/EpCAM were associated with poor prognosis in oral cancer patients from The Cancer Genome Atlas database. Our findings indicated that UBE2C might be a potential biomarker for tumorigenesis and prognosis in TSCC.

Author Correction: HSPD1 repressed E-cadherin expression to promote cell invasion and migration for poor prognosis in oral squamous cell carcinoma.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Prognostic role of RECK in pathological outcome-dependent buccal mucosa squamous cell carcinoma.

BACKGROUND: Buccal mucosal squamous cell carcinoma (BMSCC) is an aggressive oral cancer. Moreover, reversion-inducing cysteine-rich protein with Kazal motifs (RECK) is a well-known tumor suppressor in many cancers. Our aim was to investigate the association of RECK expression with prognosis in BMSCC patients with different clinicopathological features. MATERIALS AND METHODS: The expression level of RECK was determined by immunohistochemistry using tissue microarrays containing specimens from 193 BMSCC patients. The association of RECK expression with outcomes in BMSCC patients stratified by different clinicopathological features was analyzed by Cox proportional hazards models. RESULTS: The low expression level of RECK was associated with shorter disease-specific survival, especially in patients with age >40 years, moderate or poor cell differentiation, advanced pathological stage, and history of postoperative radiotherapy. However, the low expression level of RECK was not associated with poor disease-free survival, except in BMSCC patients with age ≦40 years, advanced pathological stage and lymph node metastasis. Furthermore, RECK-knockdowned cells showed higher cell viability and abilities of invasion/migration, indicating that RECK might be a tumor suppressor for tumor progression in oral cancer. CONCLUSION: The low expression of RECK might be a potential prognostic biomarker for pathological outcome-dependent BMSCC patients.

Guanylate-binding protein 6 is a novel biomarker for tumorigenesis and prognosis in tongue squamous cell carcinoma.

OBJECTIVES: Guanylate-binding protein 6 (GBP6) is a member of the guanylate-binding protein family, and its role in cancer has not yet been reported. We aimed to investigate the clinical significance of GBP6 in oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Next-generation sequencing was applied for analyzing differential gene expression profiling between corresponding tumor adjacent normal (CTAN) and tumor tissue from two paired OSCC patients. Real-time PCRs (RT-PCRs) were used to investigate the gene expression level of GBP6 of CTAN and tumor tissue samples from 14 TSCC patients. Immunohistochemistry was used to investigate the protein expression level of GBP6 in tumor tissues and paired CTAN tissues from 488 OSCC patients, including 183 buccal mucosa squamous cell carcinoma (BMSCC), 245 tongue squamous cell carcinoma (TSCC), and 60 lip squamous cell carcinoma (LSCC) patients. RESULTS: Compared with CTAN tissues of OSCC patients, GBP6 is identified as a downregulated gene using the NGS platform, which was confirmed in 14 OSCC patients by RT-PCR. Moreover, protein expression level of GBP6 in tumor tissues was lower than that in CTAN tissues and the low GBP6 expression was correlated with poor cell differentiation/lymph node metastasis in TSCC patients. In addition, TSCC patients with low expression levels of GBP6 had poor disease-specific survival rate. CONCLUSION: The low expression of GBP6 was associated with tumorigenesis and poor prognosis in OSCC patients, especially in TSCC patients. CLINICAL RELEVANCE: GBP6 may serve as a novel favorable diagnostic and prognostic biomarker in TSCC patients.

HSPD1 repressed E-cadherin expression to promote cell invasion and migration for poor prognosis in oral squamous cell carcinoma.

Buccal mucosa squamous cell carcinoma (BMSCC) is one of major subsites of oral cancer and is associated with a high rate of metastasis and poor prognosis. Heat shock proteins (HSPs) act as potential prognostic biomarkers in many cancer types. However, the role of HSPD1 in oral cancer, especially in BMSCC, is still unknown. Through data analysis with The Cancer Genome Atlas (TCGA), we found the association of HSPD1 gene expression with tumorigenesis and poor prognosis in oral cancer patients. Our cohort study showed that higher HSPD1 protein level was associated with tumorigenesis and poor prognosis in BMSCC patients with lymph node invasion, suggesting that HSPD1 may be involved in tumor metastasis. Moreover, knockdown of HSPD1 induced E-cadherin expression and decreased the migration and invasion of BMSCC cells. In contrast, ectopic expression of HSPD1 diminished E-cadherin expression and promoted the migration/invasion of BMSCC cells. Further, HSPD1 regulated RelA activation to repress E-cadherin expression, enhancing the migration and invasion of BMSCC cells. Furthermore, HSPD1 protein level was inversely correlated with E-cadherin protein level in tumor tissues and co-expression of high HSPD1/low E-cadherin showed a significant association with poor prognosis in BMSCC patients. Taken together, HSPD1 might repress E-cadherin expression and promote metastatic characters of BMSCC cells for poor prognosis of BMSCC patients.

Association of SDF-1 and CXCR4 Polymorphisms With Susceptibility to Oral and Pharyngeal Squamous Cell Carcinoma.

BACKGROUND/AIM: Long-term exposure to betel quid (BQ)-, cigarette-, and alcohol-induced chronic inflammation is a crucial risk factor for oral and pharyngeal squamous cell carcinoma (OPSCC) progression. We analyzed the genotypes of stromal-cell-derived factor-1 (SDF-1) and CXC-chemokine receptor-4 (CXCR4) and determined the association between their polymorphisms and the risk of OPSCC. MATERIALS AND METHODS: This study consisted of 452 patients with pathologically proved OPSCC and 424 sex- and age-matched cancer-free controls. The genotypes of SDF-1 and CXCR4 were detected through the TaqMan real-time polymerase chain reaction (PCR) method. RESULTS: Our data indicated that the C allele and C/C genotypes of CXCR4 were significantly associated with OPSCC [adjusted odds ratio (AOR)=1.41, 95% confidence interval (CI):1.02-1.96, p=0.037 and AOR=1.51, 95% CI:1.05-2.17, p=0.028, respectively] and OSCC (AOR=1.41, 95%CI:1.00-2.00, p=0.049 and AOR=1.49, 95%CI:1.01-2.20, p=0.044, respectively) risk. Patients with genetic polymorphisms of the genotype combination SDF-1/CXCR4 had a higher risk of OSCC (p trend=0.033). We analyzed the effects of CXCR4 genetic variants on susceptibility to OPSCC in patients with different risk habits of BQ chewing, tobacco smoking and alcohol consumption, and revealed that C/T+T/T genotypes exerted an increased risk only in patients with one (AOR=2.68, p=0.036) or two risk habits (AOR=2.02, p=0.027) compared to patients with the C/C genotype. CONCLUSION: We concluded that CXCR4 C>T can be used as a genetic marker of susceptibility to OPSCC, particularly in OPSCC patients with one or two types of risk habits with a synergistic effect.

Differential clinical significance of COL5A1 and COL5A2 in tongue squamous cell carcinoma.

BACKGROUND: Type V collagen (COL5), in the functional heterotrimer [α1(V)2 α2(V)] isoform, participates in the malignancies of various cancers. However, its role in tongue squamous cell carcinoma (TSCC) remains unclear. MATERIALS AND METHODS: The expression levels of COL5A1 and COL5A2 polypeptide chains were examined using the tissue microarray from 245 TSCC patients with immunohistochemistry. Paired t test and Wilcoxon signed-rank test were performed for comparisons among the groups. Survival rates were estimated by using the Kaplan-Meier method and compared with log-rank tests. A Cox proportional hazards model was used to evaluate the impact of protein expression level on survival rate. RESULTS: Expression level of COL5A1 was significantly increased in tumor tissues (P < 0.001) compared to that in corresponding adjacent normal tissues. High expression level of COL5A1 was associated with advanced pathological stage (III, IV, P = 0.015) and lymph node metastasis (P = 0.005) of TSCC patients. High expression level of COL5A1 was also correlated with poor disease-specific survival (DSS, P = 0.001) and disease-free survival (DFS, P = 0.003) in TSCC patients. However, high expression level of COL5A2 was correlated with better DFS in TSCC patients (P = 0.043). Moreover, co-expression level of high (COL5A1)2 /low (COL5A2) heterotrimer was correlated with worse DSS (P = 0.004) and DFS (P = 0.004). CONCLUSION: COL5A1 is an unfavorable factor for tumorigenesis, clinicopathological outcomes, and prognosis, whereas COL5A2 is only a favorable factor for prognosis in TSCC. The co-expression of high (COL5A1)2/low (COL5A2) heterotrimer is a more potential unfavorable factor for prognosis in TSCC.

Low C6orf141 Expression is Significantly Associated with a Poor Prognosis in Patients with Oral Cancer.

C6orf141 (Chromosome 6 open reading frame 141) is a novel gene, and its role in oral cancer progression remains unclear. C6orf141 expression in oral squamous cell carcinoma (OSCC) and adjacent normal tissues from 428 patients was examined through immunohistochemistry (IHC). Our results revealed that C6orf141 expression was significantly reduced in OSCC compared with adjacent normal tissues. Low C6orf141 expression was significantly associated with a poor American Joint Committee on Cancer pathological stage (P < 0.001), T classification (P = 0.002), and pN stage (P = 0.032). Kaplan-Meier curves revealed that low C6orf141 expression was significantly associated with shorter disease-specific survival (DSS) in patients with OSCC (log-rank P = 0.007). Multivariate analysis indicated that low C6orf141 expression was an independent prognostic biomarker for DSS (adjusted hazard ratio = 1.34; 95% confidence interval = 1.10-1.81; P = 0.05). Additionally, ectopic C6orf141 expression could significantly suppress oral cancer cell proliferation, colony formation, and migratory and invasive abilities. Xenograft tumor growth assay revealed that C6orf141 could significantly suppress oral tumor growth in vivo. Our results suggest that C6orf141 plays a novel tumor-suppressive role in oral cancer cell growth and motility. Furthermore, C6orf141 dysfunction could be a potential prognostic biomarker for OSCC and provide new therapeutic strategies in the future.

High snail expression predicts a poor prognosis in breast invasive ductal carcinoma patients with HER2/EGFR-positive subtypes.

BACKGROUND: High Snail expression is known as a poor prognostic factor in breast cancer. However, its prognostic impact for breast cancer with different molecular subtypes is still controversial. METHODS: Snail expression was examined by immunohistochemistry in tissue microarray slides of 85 corresponding tumor-adjacent normal (CTAN) and 247 breast invasive ductal carcinoma (IDC) tissues. Multivariable Cox regression analysis was used to assess the impact of Snail expression on survival rate by different molecular subtypes of breast IDC patients. RESULTS: The level of Snail expression in IDC tumor tissues was significantly higher than that in CTAN tissues. Moreover, high Snail expression had direct impacts on poor disease specific survival (DSS) and disease-free survival (DFS) in breast IDC patients with human epidermal growth factor receptor 2 (HER2)-positive and human epidermal growth factor receptor (EGFR)-positive statuses as well as the HER2 intrinsic subtype. Additionally, breast IDC patients with a combination of three prognostic factors, including high Snail expression and HER2-positive and EGFR-positive statuses, had much poor DSS and DFS with a statistically significant linear trend. CONCLUSION: High Snail expression could predict a poor prognosis for breast IDC patients with HER2/EGFR-positive subtypes.

Gender difference in long-term use of opioids among Taiwan officially registered patients with chronic noncancer pain.

Research regarding sex or gender difference in chronic pain proliferated in this decade. This study was to analyze gender difference in Taiwan patients receiving long-term opioids for chronic noncancer pain.An observational cross-sectional survey was conducted among the registered outpatients by the Taiwan Food and Drug Administration. Participants completed a self-report questionnaire, including the Taiwanese version of Brief Pain Inventory and enquiry regarding sexual activities, depressive symptoms, and misuse behaviors.In total, 68 female and 142 male patients were analyzed. Both pain intensity and daily function interference reduced comparably (around 50%) between women and men after taking opioids in the past 1 week. The opioid-related adverse effects, including constipation, decreased sexual desire and satisfaction, and misuse behaviors were not significantly different. Women were exceedingly diagnosed with depression (67.7% vs 49.3%, P = .012) and had a higher mean depressive symptom score in the past 1 month, especially among those age <40 years (23.3 vs 11.9, P = .009), as compared with men. In addition, women had a lower mean self-rated health score (37.9 vs 44.3, P = .047). The mean morphine equivalent dose was significantly lower in women (131.6 vs 198.2 mg/day, P = .008), which was not correlated with their depressive scores.Gender differences in the effectiveness and adverse effects of long-term opioids were not found among Taiwan registered outpatients with chronic noncancer pain. However, more female patients inclined to have a coexisting depression diagnosis, depressive symptoms, and a lower perceived health score, needing regular screening and closer monitoring.

The association between immunoexpression levels of oxidant and antioxidant enzymes and lip squamous cell carcinoma.

The aim of this study was to investigate the associations among the immunoexpression levels of manganese superoxide dismutase (Mn-SOD), glutathione peroxidase (GPx), and myeloperoxidase (MPO) in lip squamous cell carcinoma (LSCC) tissues and the clinicopathological characteristics, and prognostic factors in patients with LSCC. The immunoexpression levels of Mn-SOD, GPx, and MPO were examined in 76 LSCC tissue samples using immunohistochemical staining on tissue microarray slides, and compared to those in normal lip mucosa adjacent to venous lakes (normal controls), normal tissue adjacent to corresponding tumors (NTACT), and recurrent tumors. Associations between immunoexpression levels and clinicopathological characteristics were analyzed using the Student's t-test. The prognostic factors were analyzed using Cox regression. The immunoexpression levels of Mn-SOD, GPx, and MPO were significantly different among the normal controls, NTACTs, tumors, and recurrent tumors (Mn-SOD: p = 0.001, GPx: p < 0.001, MPO: p < 0.001). Lower lip cancer was associated with higher Mn-SOD immunoexpression levels (p = 0.04) and probably indicated higher oxidative stress. Lymph node involvement with a lower immunoexpression level of MPO (p = 0.007) indicated compensatory mechanism to attenuate oxidative damage. A low Mn-SOD immunoexpression level was borderline significantly associated with a worse prognosis for disease-specific survival, and it was probably related to a lower capacity for coping with oxidative stress.

Isocitrate dehydrogenase 1-snail axis dysfunction significantly correlates with breast cancer prognosis and regulates cell invasion ability.

BACKGROUND: The isocitrate dehydrogenase (IDH) gene family expresses key functional metabolic enzymes in the Krebs cycle and mediates the epigenetic reprogramming, which serves as an important biomarker of breast cancer. However, the expression levels of the IDH protein and their biological function in human breast cancer remain largely unknown. METHODS: In this study, the clinical impact of IDH1 expression on the progression and prognosis of breast cancer was evaluated using immunohistochemistry assay (IHC) of the corresponding tumor-adjacent normal, ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC) tissues from 309 patients with breast ductal carcinoma. The relationship between microRNA (miRNA) and IDH1 were examined by a bioinformatics approach, western blot and reporter assay. The biological functions of IDH1 were examined in breast cancer cells with IDH1 knockdown, including proliferation, migration and invasion. RESULTS: The present findings revealed that the mRNA and protein expression levels of IDH1 were both significantly lower in breast cancer tissues than in adjacent normal tissues. A low expression level of IDH1 in breast cancer significantly correlated with advanced stage (p = 0.012), lymph node metastasis (p = 0.018), and poor disease-specific survival (DSS) (adjusted hazard ratio (AHR), 1.57, 95% confidence interval (CI), 1.08-2.30; p = 0.02). Furthermore, oncogenic miR-32 and miR-92b were identified to suppress IDH1 expression, leading to the inhibition of cell migration and invasion. We further explored whether reduced expression of IDH1 significantly increases snail expression by activating HIFα (hypoxia-inducible factor-1 alpha) and NFκB (nuclear factor kappa B) signaling. Multivariate Cox regression analysis revealed that the combination of low IDH1 and high snail expression could be an independent risk factor for shorter DSS (AHR, 2.34; 95% CI, 1.32-4.16; p = 0.004) and shorter disease-free survival (AHR, 2.50; 95% CI, 1.39-4.50; p = 0.002) in patients with breast cancer. CONCLUSION: Our findings revealed that a IDH1low/Snailhigh molecular signature could serve as an independent biomarker for poor prognosis in breast cancer.

Caspase-3 expression in tumorigenesis and prognosis of buccal mucosa squamous cell carcinoma.

Buccal mucosa squamous cell carcinoma (BMSCC) is the most common oral cancer in Southeast Asia. Caspase-3, a key molecule in regulating apoptosis, promotes the malignancy of various cancers. However, its role in BMSCC is unknown. Herein, we evaluated the association of caspase-3 expression with tumorigenesis and prognosis in BMSCC patients. Immunohistochemical staining indicated that the expression levels of cleaved caspase-3 (p<0.001) and caspase-3 (p<0.001) in 185 BMSCC tissues were significantly higher compared to those in the tumor adjacent normal tissues. Moreover, the high expression of caspase-3 was associated with poor pathological outcomes [advanced pathological stage (p=0.029) and larger tumor size (p=0.002)] and poor disease-free survival in patients receiving postoperative radiotherapy (p=0.030). Moreover, the low co-expression of cleaved caspase-3 and caspase-3 was associated with better disease-specific survival in patients with early pathological stage (I + II, p=0.018) or without lymph node invasion (p=0.043) compared to the positive/high expression of either or both cleaved caspase-3 and caspase-3. Taken together, cleaved caspase-3 and caspase-3 could be biomarkers for tumorigenesis in BMSCC patients. Cleaved caspase-3 and/or caspase-3 might be prognostic biomarkers for certain stages of BMSCC.

Clinicopathological study of lip cancer: a retrospective hospital-based study in Taiwan.

To evaluate the clinicopathological characteristics, high-risk lifestyle factors (HRLF: chronic exposure to sun, betel quid, alcohol, and tobacco), and prognostic factors of lip cancer. The hospital records of patients with pathologically confirmed lip squamous cell carcinoma (LSCC, n = 112) and lip basal cell carcinoma (LBCC, n = 21) were reviewed. Differences in clinicopathological characteristics between LSCC and LBCC, upper and lower lip, and status of second primary tumors were compared by chi-square test and logistic regression. The prognostic factors for LSCC were analyzed by Cox regression. Compared with LBCC patients, LSCC patients were men-predominant (p < 0.001), had younger ages at onset (p < 0.001), and higher rates of lower lips involvement (p < 0.001) and HRLFs. Patients with second primary tumors were highly associated with lower lip cancer involvement (adjusted odds ratio = 2.91, p = 0.03). Patients with lower lip cancer had more HRLFs with an increasing linear trend (p = 0.004). The poorer prognostic factors of LSCC for disease-specific survival were advanced stage III/IV [crude hazard ratio (CHR) = 11.16, p < 0.001], tumor dimension >4 cm (CHR = 8.19, p = 0.006), lymph node involvement (CHR = 11.48, p < 0.001), and recurrence (CHR = 3.96, p = 0.01); whereas for disease-free survival were moderately to poorly differentiated LSCC (CHR = 4.97, p = 0.002) and alcohol consumption (CHR = 3.13, p = 0.04). LSCC and lower lip cancer were highly associated with HRLFs.

The variant of pri-mir-26a-1 polymorphism is associated with decreased risk of betel quid-related oral premalignant lesions and oral squamous cell carcinoma.

OBJECTIVES: This case-control study evaluated the association of the single nucleotide polymorphism rs7372209 (T>C) in pri-mir-26a-1 with the risk and progression of betel quid (BQ)-related oral premalignant lesions (OPLs) and oral squamous cell carcinoma (OSCC). STUDY DESIGN: In total, 597 BQ chewers were recruited: 196 healthy controls, 241 patients with OPLs, and 160 patients with OSCC. Genotypes were determined using the TaqMan real-time assay. RESULTS: The C/T + T/T genotypes and T allele in pri-mir-26a-1 were correlated with a decreased risk of BQ-related OPLs (P = .038 and .005, respectively), oral leukoplakia (P = .01 and .001, respectively), and advanced-stage OSCC (P = .021 and .004, respectively). The effects of the C/T + T/T genotypes and T allele on the decreased risk of OPLs were potent in the older age group (both Pinteraction < .001), heavy smokers (Pinteraction ≤ .003 and .006, respectively) and alcohol drinkers (Pinteraction ≤ .004 and .001, respectively). Furthermore, among patients with OSCC, the C/T + T/T genotypes and T allele were associated with a decreased risk of advanced pathologic stage (P = .032) and lymph node involvement (P = .017). CONCLUSIONS: BQ chewers carrying the T allele or C/T + T/T genotypes in pri-mir-26a-1 may have a decreased risk of oral leukoplakia, OPLs, and advanced-stage OSCC.