An Integrative ATAC-Seq and RNA-Seq Analysis of the Endometrial Tissues of Meishan and Duroc Pigs.

Meishan pigs are a well-known indigenous pig breed in China characterized by a high fertility. Notably, the number of endometrial grands is significantly higher in Meishan pigs than Duroc pigs. The characteristics of the endometrial tissue are related to litter size. Therefore, we used the assay for transposase-accessible chromatin with sequencing (ATAC-seq) and RNA-sequencing (RNA-seq) to analyze the mechanisms underlying the differences in fecundity between the breeds. We detected the key transcription factors, including Double homeobox (Dux), Ladybird-like homeobox gene 2 (LBX2), and LIM homeobox 8 (Lhx8), with potentially pivotal roles in the regulation of the genes related to endometrial development. We identified the differentially expressed genes between the breeds, including SOX17, ANXA4, DLX3, DMRT1, FLNB, IRF6, CBFA2T2, TFCP2L1, EFNA5, SLIT2, and CYFIP2, with roles in epithelial cell differentiation, fertility, and ovulation. Interestingly, ANXA4, CBFA2T2, and TFCP2L1, which were upregulated in the Meishan pigs in the RNA-seq analysis, were identified again by the integration of the ATAC-seq and RNA-seq data. Moreover, we identified genes in the cancer or immune pathways, FoxO signaling, Wnt signaling, and phospholipase D signaling pathways. These ATAC-seq and RNA-seq analyses revealed the accessible chromatin and potential mechanisms underlying the differences in the endometrial tissues between the two types of pigs.

Clinical and Molecular Characteristics and Antibacterial Strategies of Klebsiella pneumoniae in Pyogenic Infection.

Treatment of Klebsiella pneumoniae causing pyogenic infections is challenging. The clinical and molecular characteristics of Klebsiella pneumoniae causing pyogenic infections are poorly understood, and antibacterial treatment strategies are limited. We analyzed the clinical and molecular characteristics of K. pneumoniae from patients with pyogenic infections and used time-kill assays to reveal the bactericidal kinetics of antimicrobial agents against hypervirulent K. pneumoniae (hvKp). A total of 54 K. pneumoniae isolates were included, comprising 33 hvKp and 21 classic K. pneumoniae (cKp) isolates, and the hvKp and cKp isolates were identified using five genes (iroB, iucA, rmpA, rmpA2, and peg-344) that have been applied as hvKp strain markers. The median age of all cases was 54 years (25th and 75th percentiles, 50.5 to 70), 62.96% of individuals had diabetes, and 22.22% of isolates were sourced from individuals without underlying disease. The ratios of white blood cells/procalcitonin and C-reactive protein/procalcitonin were potential clinical markers for the identification of suppurative infection caused by hvKp and cKp. The 54 K. pneumoniae isolates were classified into 8 sequence type 11 (ST11) and 46 non-ST11 strains. ST11 strains carrying multiple drug resistance genes have a multidrug resistance phenotype, while non-ST11 strains carrying only intrinsic resistance genes are generally susceptible to antibiotics. Bactericidal kinetics revealed that hvKp isolates were not easily killed by antimicrobials at susceptible breakpoint concentrations compared with cKp. Given the varied clinical and molecular features and the catastrophic pathogenicity of K. pneumoniae, it is critical to determine the characteristics of such isolates for optimal management and effective treatment of K. pneumoniae causing pyogenic infections. IMPORTANCE Klebsiella pneumoniae may cause pyogenic infections, which are potentially life-threatening and bring great challenges for clinical management. However, the clinical and molecular characteristics of K. pneumoniae are poorly understood, and effective antibacterial treatment strategies are limited. We analyzed the clinical and molecular features of 54 isolates from patients with various pyogenic infections. We found that most patients with pyogenic infections had underlying diseases, such as diabetes. The ratio of white blood cells to procalcitonin and the ratio of C-reactive protein to procalcitonin were potential clinical markers for differentiating hypervirulent K. pneumoniae strains from classical K. pneumoniae strains that cause pyogenic infections. K. pneumoniae isolates of ST11 were generally more resistant to antibiotics than non-ST11 isolates. Most importantly, hypervirulent K. pneumoniae strains were more tolerant to antibiotics than classic K. pneumoniae isolates.

Applications of the Crenel Lateral Interbody Fusion Procedure in Treatment for Adjacent Segments Degeneration of the Lumbar Spine.

OBJECTIVE: To observe the clinical and radiological effect of crenel lateral interbody fusion (CLIF) procedure in the management of lumbar spine adjacent segment degenerative (ASD). METHODS: Thirty-seven patients with lumbar spine ASD who underwent the CLIF procedure between June 2018 and December 2019 were included in the study. There were 13 males and 24 females, with a mean age of 64.30 ± 5.92 years. The VAS score of the back (VAS_Back) and legs (VAS_Leg), Oswestry Disability Index (ODI) score, the height of the intervertebral space (HIS), the height of the intervertebral foramen (HIF), the cross-sectional area (CSA) of the vertebral canal, segmental lordosis (SL), and lumbar lordosis (LL) were recorded before the operation, 2 weeks after the operation, 3 months after the operation, and at the last follow-up respectively. Clinical and radiological outcomes before and after the surgery were compared, and correlation and regression analyses were performed. RESULTS: There were no vascular and nerve-related complications during the operation. The average follow-up time was 16.63 ± 4.24 months. The median of both VAS_Back and VAS_Leg was 7 before surgery and 1 at the last follow-up. Meanwhile, the average preoperative ODI score, HIS, HIF, CSA of the vertebral canal, LL, and SL was (67.48 ± 7.17) %, (4.80 ± 0.73) mm, (12.95 ± 2.07) mm, (59.52 ± 9.22) mm2 , (37.22 ± 5.92)° and (4.78 ± 1.99)°, respectively. At the final follow-up, ODI score, HIS, HIF, CSA of the vertebral canal, LL, and SL was (7.07 ± 2.66) %, (9.44 ± 0.61) mm, (17.30 ± 1.90) mm, (70.49 ± 8.95) mm2 , (44.67 ± 6.38)° and (13.44 ± 3.27)°, respectively. In the VAS_Back, VAS_Leg, ODI score, LL, SL, HIS, HIF, and CSA of the vertebral canal, the difference between preoperative and 2 weeks after the operation, 3 months after the operation, and the last follow-up were statistically significant (P < 0.05). However, the difference was not statistically significant between each time point after the operation in the CSA of the vertebral canal, LL, and SL (P > 0.05). Nonetheless, the difference was statistically significant in ODI between each time point after the operation (P < 0.05). VAS_Leg was associated with HIS, HIF, and CSA of the vertebral canal, while LL and SL were risk factors for low back pain. CONCLUSION: Crenel lateral interbody fusion is an effective procedure in the management of lumbar ASD. Not only was the postoperative swift recovery due to minimal invasion, but also adequate LL and SL were achievable.

Clinical and Microbiological Characterization of Bloodstream Infections Caused by Mycoplasma hominis: An Overlooked Pathogen.

INTRODUCTION: Bloodstream infection (BSI) is associated with high mortality rates. Mycoplasma hominis, which rarely causes extragenital infections, has been shown to induce BSI and presents a clinical diagnostic and therapeutic challenge. METHODS: In this study, we investigated the clinical characteristics, antibiotic resistance, and multilocus sequence typing (MLST) of eight BSI cases caused by M. hominis in South China from January 2018 to October 2021. RESULTS: Underlying immunosuppression and genitourinary tract surgery are important risk factors for M. hominis BSI. The most prevalent clinical symptoms and signs were fever. Additional findings included elevated neutrophil count and C-reactive protein level. Furthermore, in this study, all the patients had erythrocytopenia. M. hominis harbored the highest rate of resistance to levofloxacin (75.0%), followed by sparfloxacin (50.0%), and gatifloxacin (37.5%). gyrA S153L was the most frequent mutation in levofloxacin-resistant strains, followed by parC S91I. parC K144R may be related to resistance to gatifloxacin and sparfloxacin. Eight strains showed sensitivity to all the other antibiotics analyzed (doxycycline, minocycline, josamycin, and clindamycin). MLST was performed in seven isolates, and seven new sequence types were described. We compared our isolates with all M. hominis strains from the PubMLST database, and one major clonal complex and eight singletons were identified. CONCLUSIONS: Our study clarified and expanded the clinical features and antibiotic resistance of M. hominis BSI. These findings are useful for the clinical diagnosis and control of M. hominis BSI.

Exosomal miRNAs as Biomarkers of Cancer: a Meta-Analysis.

BACKGROUND: Tumor-derived exosomal miRNAs secreted by cancer cells play significant roles in the pathological processes of cancer, but no systematic meta-analysis has focused on the diagnostic efficiency of exosomal miRNAs. This meta-analysis assessed the diagnostic value of circulating exosomal miRNA in cancer. METHODS: Studies evaluating the diagnostic value of exosomal miRNA were identified in EMBASE, PubMed, Cochrane Library, and Web of Science up to August 1, 2018. The quality of each study was assessed according to the Quality Assessment of Diagnostic Accuracy Studies 2, and STATA 14.0 was used for the analyses. The true positive (TP), false positive (FP), true negative (TN), and false negative (FN) rates were extracted from each study to obtain the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and their 95% confidence intervals (CIs). RESULTS: The meta-analysis included 16 studies with 1,591 patients. Five studies reported sensitivity values, and the pooled sensitivity was 0.86 (95% CI = 0.80 - 0.90, while 29 studies reported specificity values, and the pooled specificity was 0.89 (95% CI = 0.83 - 0.93). The pooled PLR was 7.8 (95% CI = 4.9 - 12.4), the pooled NLR was 0.16 (95% CI = 0.11 - 0.24), the pooled DOR was 48 (95% CI = 23 - 101), and the AUC was 0.94 (0.91 - 0.96). CONCLUSIONS: Our meta-analysis indicated that body fluid exosomal miRNAs are highly accurate for distinguishing patients from healthy individuals, and exosomal miRNAs have superior diagnostic value in plasma, prostate cancer patients, and non-Asian individuals.

Human papillomavirus genotypes and p16 expression in oral leukoplakia and squamous cell carcinoma.

Several studies have shown a broad variation in the prevalence of human papillomavirus (HPV) in oral leukoplakia (OLK) and oral squamous cell carcinoma (OSCC), whereas the relationship is less well-defined and specific HPV genotypes lack examination in OLK. In the present study, the role of HPV and surrogate p16 expression was investigated to explore the correlation and pathogenesis in OLK and OSCC. Polymerase chain reaction (PCR) and flow-through hybridization technology were utilized to detect HPV genotypes in oral exfoliated cells from 30 healthy volunteers, 103 OLK and 30 OSCC patients. Expression of p16 was assessed by immunohistochemistry (IHC) in biopsies from these OLK and OSCC, in addition to 15 normal oral mucosal tissues as the control group. The healthy controls showed 3.3% (1/30) HPV presence; In OLK and OSCC, the detection rate was 4.9% (5/103), 3.3% (1/30), respectively. No significant relationship between HPV and OLK or OSCC was observed when compared with the control group (P>0.05). All 6 HPV-positive OLK and OSCC cases had p16 overexpression. But the sensitivity of p16 IHC was poor, because 88.4% (38/43) of p16 over-expressed OLK were HPV negative. There was no statistical significance between HPV and the sex, age, site, alcohol consumption, or smoking. These findings suggested HPV had a low prevalence in OLK and OSCC. This suggests the detection of HPV genotypes by PCR in exfoliated cells combined with p16 IHC may be more accurate to represent HPV infection.

[Pharmacokinetics mechanism of ABC efflux proteins-mediated seven features of compatibility].

ABC efflux proteins are a kind of transporters mediating diversified endogenous and exogenous efflux protein substrates across the plasma membrane by depending on the chemical energy released by ATP hydrolysis. As a vitally important functional membrane, it is widely found in various tissues and organs. The drug changes the expressions and/or functions of the transport proteins, which will affect the disposal process of substrate drugs corresponding to transporters in vivo, and finally lead to the pharmacokinetic interactions. The efflux proteins take part in the absorption, distribution, metabolism and excretion of drugs, and mainly consist of P-glycoprotein(P-gp), multidrug resistance associated protein(MRP) and breast cancer resistance protein(BCRP). The induction effect or inhibition effect of drugs on efflux protein plays a greatly significant role in the drug interaction produced by the compatibility of traditional Chinese medicine, which may be one of the important mechanisms of the theory of seven features of compatibility. In this article, the effects of seven features of compatibility on the ABC efflux transporters were reviewed, in order to reveal the roles of efflux protein in the herb-pairs compatibility, and provide new ideas for the mechanism and rationality of herb compatibility.

[Research progress of quantitative DNA analysis in oral carcinoma and precancerous lesions].

Normal individual cells had 23 pairs of chromosome and stable DNA content. DNA content was varied during malignant transformation, which was specific feature of tumor. Quantitative DNA analysis can reflect cellular physiological or pathological condition by nuclear DNA content, which had significant role in early diagnosis, predication of prognosis and treatment selection. This article summarized the research progress of quantitative DNA analysis in oral carcinoma and precancerous lesions in recent years.

MicroRNA-155 in oral squamous cell carcinoma: Overexpression, localization, and prognostic potential.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a common malignancy with poor prognosis. MicroRNAs (miRNAs) play an important role in cancer, but their role in OSCC is not clarified. METHODS: We performed miRNA microarray, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and fluorescence in situ hybridization (FISH) to examine miRNA expression in OSCC and paired adjacent cancer-free mucosal (ACF) tissues. RESULTS: Thirteen miRNAs, including miRNA-155, were upregulated (>2-fold) in OSCC against ACF. MiRNA-155 was confirmed to have significantly higher expression in OSCC against ACF (paired-samples t test; p = .041) and it was localized in the cancer nest, inflammatory area, and vascular endothelium of OSCC. High expression of miRNA-155 in ACF tissue was an independent prognostic indicator for OSCC survival. CONCLUSION: MiRNA-155 was overexpressed in OSCC and it was located in the cancer nest, inflammatory area, and vascular endothelium of OSCC. High miRNA-155 expression level in ACF may predict poor prognosis in patients with OSCC.

[The effect of retrovirus-mediated hTRT transfection into cultured oral keratinocytes].

PURPOSE: Human telomerase reverse transcriptase (hTRT) was transfected into cultured oral keratinocytes (OKC) mediated by pBABE-tert recombined retrovirus to investigate the effect on OKC lifespan. METHODS: pBABE-tert recombined retrovirus loaded with hTRT gene was amplified by transfected PT67 cells, and then transfected into cultured OKC in vitro. The positive clones of OKC were separated by puromycin and subcultured. Telomerase activity was analyzed by telomerase PCR-ELISA and PCR-PAGE. RESULTS: The hTRT positive clones of OKC showed telomerase expression, with extending lifespan to 8-9 passages. CONCLUSIONS: The hTRT transfected OKC can prolong doubly lifespan but not be immortalized, which indicates that cellular immortality mechanism is complicated and multi-controled. Telomerase activity is the key for cell immortalization but not the only impact factor.

Expression patterns of cancer stem cell markers ALDH1 and CD133 correlate with a high risk of malignant transformation of oral leukoplakia.

Molecular markers for predicting oral cancer development in premalignant oral leukoplakia (OL) are urgently needed. The objective of this study was to examine the expression patterns of cancer stem cell markers ALDH1 and CD133 in samples from patients with OL, and determine their prognostic values for subsequent development of oral cancer. Immunohistochemistry for ALDH1 and CD133 was performed in samples from a cohort of 141 patients with biopsy-proven OL who received a mean follow-up of 5.5 years. Patient clinicopathologic and follow-up data were analyzed. Expression of ALDH1 and CD133 was observed in 54 (38.3%) and 32 (22.7%) of 141 patients with OL, respectively. Kaplan-Meier analysis showed that 48.1% patients with ALDH1-positivity developed oral cancer compared with 12.6% those with ALDH1-negativity (p < 0.001). Meanwhile, 59.4% patients with CD133-positivity developed oral cancer compared with 16.5% those with CD133-negativity (p < 0.001). Multivariate analysis revealed that ALDH1 and CD133 expression was associated with 4.17-fold [95% confidence interval (CI), 1.96-8.90; p < 0.001] and 2.86-fold (95% CI, 1.48-5.55; p = 0.002) increased risk of OL transformation, respectively. Collectively, these data demonstrated for the first time that the expression of ALDH1 and CD133 correlated with malignant transformation in a large series of patients with OL who received a long-term follow-up, which suggests that they may serve as predictors to identify OL with a high risk of oral cancer development.

Phospholipase C-γ1 expression correlated with cancer progression of potentially malignant oral lesions.

BACKGROUND: Phospholipase C-γ1 (PLCγ1) is required for cellular migration during tumor progression and invasion of oral squamous cell carcinoma (OSCC) cells. The objective of the current study was to determine immunoexpression pattern of PLCγ1 in oral potentially malignant lesions (OPLs) and evaluate PLCγ1 usefulness as a biomarker for predicting clinical behavior in the carcinogenesis of OPL. METHODS: In a retrospective follow-up study, the expression pattern of PLCγ1 protein was determined using immunohistochemistry in samples from 68 patients, including untransformed cases (n = 38) and malignant-transformed cases (n = 30). The corresponding post-malignant lesions (OSCCs) were also performed. RESULTS: We observed that elevated expression of PLCγ1 in 40 of 68 (59%) general OPLs and 23 of 30 (77%) OSCCs compared with that in normal oral mucosa. Kaplan-Meier analysis revealed that patients with PLCγ1 positivity had a significantly higher incidence of OSCC than those with PLCγ1 negativity. Cox regression analysis revealed that PLCγ1 expression patterns were significantly associated with increased risk of malignant progression. In addition, the correlation between PLCγ1 expression in pre-malignant OPL and that in post-malignant OSCC was significant (P = 0.004). CONCLUSION: These data indicate that PLCγ1 expression in OPL correlated with oral cancer progression, and PLCγ1 may serve as a useful marker for the identification of high-risk OPL into OSCC.

Expression of cancer stem cell markers ALDH1 and Bmi1 in oral erythroplakia and the risk of oral cancer.

BACKGROUND: Oral erythroplakia (OE) is a notoriously aggressive oral pre-malignant lesion with a high tendency to oral cancer development, but its biological behavior is largely unknown. The objective of this study was to determine the expression of cancer stem cell markers ALDH1 and Bmi1 in OE and their correlation with malignant transformation of OE. METHODS: In a retrospective case-control study, expression patterns of ALDH1 and Bmi1 were determined using immunohistochemistry in samples from 34 patients with OE, including patients with untransformed lesions (n=17) and patients with malignant transformed lesions (n=17). RESULTS: ALDH1 and Bmi1 expression was observed in 19 (55.9%) and 20 (58.8%) of 34 patients with OE, respectively. Multivariate analysis revealed that ALDH1 expression was significantly associated with increased risk of transformation (P<0.05), but Bmi1 expression was not a significant marker (P > 0.05). Notably, the coexpression of both ALDH1 and Bmi1 was a strong indicator associated with 8.56-fold (95% confidence interval [CI], 1.74-42.17; P<0.01) for malignant transformation. Point prevalence analysis revealed that 78.6% (95% CI, 54.0-100) of the patient with coexpression of both ALDH1 and Bmi1 developed oral cancer. CONCLUSION: Our data indicated that the expression patterns of ALDH1 and Bmi1 in OE were associated with malignant transformation, suggesting that they may be valuable predictors for evaluating the risk of oral cancer.

Upregulation of miR-31* is negatively associated with recurrent/newly formed oral leukoplakia.

BACKGROUND: Oral leukoplakia (OLK) is a potentially malignant disorder of the oral cavity. However, the underlying mechanism of OLK is still unclear. In this study, we explore possible miRNAs involved in OLK. METHODOLOGY/PRINCIPAL FINDINGS: Using miRNA microarrays, we profiled miRNA expression in OLK and malignantly transformed OLK (mtOLK) tissue samples. The upregulation of miR-31*, miR-142-5p, miR-33a, miR-1259, miR-146b-5p, miR-886-3p, miR-886-5p, miR-519d, and miR-301a along with the downregulation of miR-572, miR-611, miR-602, miR-675, miR-585, miR-623, miR-637, and miR-1184 in mtOLK were new observations. Fluorescence in situ hybridization (FISH) analyses confirmed that miR-31* is highly expressed in mtOLK. There was a significant difference between the FISH score (p<0.05) in patients with or without recurrent/newly formed OLK. Functional analyses demonstrated that a miR-31* inhibitor decreased apoptosis in the Leuk-1, which is an immortalized oral epithelial cell line spontaneously derived from an oral leukoplakia lesion. miR-31* regulated apoptosis, cell proliferation, migration, and invasion in the HOIEC, which is a HPV E6/E7-immortalized oral epithelial cell line. Furthermore, miR-31* modulated the biological functions of apoptosis, cell proliferation, cell cycle, migration, and invasion in the oral squamous cell carcinoma cell line, Cal-27. Using bioinformatic analyses and dual luciferase reporter assays, we determined that the 3' untranslated region of fibroblast growth factor 3 (FGF3) is the target of miR-31*. Expression of FGF3 was downregulated or upregulated in the presence of a miR-31* mimic or inhibitor, respectively. CONCLUSIONS/SIGNIFICANCE: Upregulation of miR-31* is negatively associated with recurrent/newly formed OLK. MiR-31* may exert similar but distinguishable effects on biological function in oral cells with different malignant potential. FGF3 is the target of miR-31*. miR-31* may play an important role during OLK progression through regulating FGF3. MiRNA* strands may also have prominent roles in oral carcinogenesis.

A retrospective clinicopathological study on oral lichen planus and malignant transformation: analysis of 518 cases.

OBJECTIVE: To investigate the epidemiological and clinical characteristics of a relatively large cohort of patients with oral lichen planus (OLP) from eastern China. STUDY DESIGN: A total of 518 patients with histologically confirmed OLP in a long-term follow-up period (6 months-21.5 years) were retrospectively reviewed in our clinic. RESULTS: Of the 518 patients, 353 females and 165 males were identified. The average age at diagnosis was 46.3 years (range 9-81 years) with the buccal mucosa being the most common site (87.8%). At initial presentation, white lichen and red lichen was seen in 52.3% and 47.7% patients, respectively. Of these, 5 (0.96%) patients previously diagnosed clinically and histopathologically as OLP developed oral cancer. All of them were the females with no a history of smoking or alcohol use. CONCLUSIONS: Clinical features of eastern Chinese OLP patients were elucidated. Notably, approximately 1% of OLP developed into cancer, which provides further evidence of potentially malignant nature of OLP.

Oral cancer development in patients with leukoplakia--clinicopathological factors affecting outcome.

BACKGROUND: Oral leukoplakia (OL) is the best-known potentially malignant disorder. The objective of the current study was to evaluate the clinicopathological factors predictive of outcome in a large cohort of patients with OL, and report our experience in the early detection of malignant events. METHODS: A total of 320 patients with biopsy-proven OL were retrospectively reviewed from the study institution who had a mean follow-up of 5.1 years. Data on patient and lesion at initial diagnosis and patient underwent sequential biopsies were reviewed. Multiple biopsies indicates > = 3 times sequential biopsies. Oral cancer-free survival rate (OCFS) was determined by the Kaplan-Meier method and significant factors were identified by Cox regression analysis. RESULTS: The 3-year and 5-year OCFS was 86.6% and 82.0%, respectively. A new binary system of grading oral dysplasia was performed and Kaplan-Meier analysis indicated that high-grade dysplasia had significantly higher malignant incidence than low-grade dysplasia (5-year OCFS, 90.5% vs 59.0%; P<0.001), especially during the first 2-3 years of follow-up. Multivariate analysis revealed that the 4 factors including patient aged >60 years, lesion located at lateral/ventral tongue, non-homogenous lesion, high-grade dysplasia were independent significant indicators for OL malignant transformation. In addition, significant positive correlation between the multiple biopsies and these 4 factors and malignant outcome was established. CONCLUSIONS: Elderly patients with OL located at lateral/ventral tongue and who had non-homogenous lesion with high-grade dysplasia correlated much higher risk of transformation. This high-risk subpopulation was suggested to undergo sequential biopsies and histologic examination contributing to early detection of malignant event.

Expression of podoplanin and ABCG2 in oral erythroplakia correlate with oral cancer development.

Oral erythroplakia (OE) is a notoriously aggressive oral premalignant lesion with a high tendency to oral cancer development, but it's biological behavior is largely unknown. The objective of the current study was to determine podoplanin and ABCG2 immunoexpression in OE and both correlation to malignant transformation of OE. In a retrospective follow-up study, the expression patterns of podoplanin and ABCG2 were determined using immunohistochemistry in samples from 34 patients with OE, including patients with untransformed lesions (n=17) and patients with malignant transformed lesions (n=17). Podoplanin and ABCG2 expression was observed in 15 (44.1%) and 21 (61.8%) of 34 patients, respectively. Multivariate analysis revealed that podoplanin and ABCG2 expression was associated with 6.31-fold (95% confidence interval [CI], 1.02-38.92; P=0.047) and 14.39-fold (95% CI, 2.02-102.29; P=0.008) increased the risk of transformation, respectively. Point prevalence analysis revealed that 90.9% (95% CI, 70.7-100) of the patient with both podoplanin and ABCG2 positivity developed oral cancer. Collectively, our data indicated that the expression patterns of podoplanin and ABCG2 in OE were associated with oral cancer development, suggesting that podoplanin and ABCG2 may be valuable predictors for evaluating oral cancer risk.

Phosphorylated p120-catenin expression has predictive value for oral cancer progression.

AIMS: Recent studies have shown that phosphorylation of p120-catenin (p120) promotes progression and invasion of oral squamous cell carcinoma (OSCC) cells. The objective of the current study was to evaluate the usefulness of phosphorylated p120-catenin (pp120) as a biomarker for predicting clinical behaviour in the carcinogenesis of potentially malignant oral lesions. METHODS: In a retrospective follow-up study, the expression pattern of pp120 protein was determined using immunohistochemistry in samples from 68 patients with potentially malignant oral lesions, including patients with untransformed lesions (n=38) and patients with malignant transformed lesions (n=30). Analysis of corresponding post-malignant lesions (OSCCs) was also performed. RESULTS: There was high expression of pp120 in 35 of 68 (51.5%) of general potentially malignant oral lesions and 23 of 30 (76.7%) of OSCCs compared with expression in normal oral mucosa. Kaplan-Meier analysis revealed that patients with potentially malignant oral lesions expressing high levels of membranous pp120 had a significantly higher incidence of OSCC than those expressing low expressing pp120 (p=0.002; log-rank test). Cox regression analysis revealed that this pp120 expression pattern was significantly associated with a 3.43-fold increase in the risk of malignant progression (p=0.007). In addition, there was a significant correlation between high levels of membranous expression of pp120 in pre-malignant lesions and cytoplasmic expression in post-malignant lesions (p=0.028). CONCLUSIONS: The data indicated that a high level of membranous expression of pp120 in potentially malignant oral lesions is an early event during oral carcinogenesis, and that the mislocalisation of expression of pp120 from the cell membrane to the cytoplasm is associated with oral cancer progression. pp120 may serve as a useful marker for the identification of a high risk of potentially malignant oral lesions progressing to OSCC.

Two stem cell markers, ATP-binding cassette, G2 subfamily (ABCG2) and BMI-1, predict the transformation of oral leukoplakia to cancer: a long-term follow-up study.

BACKGROUND: Although oral leukoplakia (OL) is the best-known potentially malignant disorder, the risk of OL malignant transformation is difficult to assess. ATP-binding cassette, G2 subfamily (ABCG2) and BMI-1 are stem cell markers that have been found to be associated with head and neck tumorigenesis. The objective of the current study was to evaluate the usefulness of ABCG2 and BMI-1 in predicting OL transformation. METHODS: In a retrospective cohort of 135 patients with OL from the study institution who had a mean follow-up of 5.5 years, 32 developed cancer between 1985 and 2008. The expression of ABCG2 and BMI-1 was determined using immunohistochemistry in samples from these patients, and included untransformed OL (n = 103) and malignant-transformed OL (n = 32). The association between protein expression and clinicopathological parameters and transformation was analyzed. RESULTS: Expression of ABCG2 and BMI-1 was observed in 58 (43.0%) and 44 (32.6%) of 135 patients, respectively. The correlation between ABCG2 and BMI-1 expression was significant (P = .024). Kaplan-Meier analysis revealed that 37.9% of patients with ABCG2 positivity developed cancer compared with 13.0% of patients with ABCG2 negativity (P = .014, log-rank test). Approximately 40.9% of patients with BMI-1 positivity developed cancer compared with 15.4% of patients with BMI-1 negativity (P = .029, log-rank test). Multivariate analysis revealed that ABCG2 and BMI-1 expression was associated with a 3.24-fold (95% confidence interval [95% CI], 1.31-7.98; P = .011) and 4.03-fold (95% CI, 1.59-10.26; P = .003) increased the risk of transformation, respectively. CONCLUSIONS: ABCG2 and BMI-1 expression was found to be associated with the development of oral cancer in a large cohort of patients with OL for whom long-term follow-up was available, which suggests that ABCG2 and BMI-1 may be used as predictors of OL transformation.