ABSTRACT
Most cases of oral squamous cell carcinoma (OSCC) develop from visible oral potentially malignant disorders (OPMDs). The latter exhibit heterogeneous subtypes with different transformation potentials, complicating the early detection of OSCC during routine visual oral cancer screenings. To develop clinically applicable biomarkers, we collected saliva samples from 96 healthy controls, 103 low-risk OPMDs, 130 high-risk OPMDs, and 131 OSCC subjects. These individuals were enrolled in Taiwan's Oral Cancer Screening Program. We identified 302 protein biomarkers reported in the literature and/or through in-house studies and prioritized 49 proteins for quantification in the saliva samples using multiple reaction monitoring-MS. Twenty-eight proteins were successfully quantified with high confidence. The quantification data from non-OSCC subjects (healthy controls + low-risk OPMDs) and OSCC subjects in the training set were subjected to classification and regression tree analyses, through which we generated a four-protein panel consisting of MMP1, KNG1, ANXA2, and HSPA5. A risk-score scheme was established, and the panel showed high sensitivity (87.5%) and specificity (80.5%) in the test set to distinguish OSCC samples from non-OSCC samples. The risk score >0.4 detected 84% (42/50) of the stage I OSCCs and a significant portion (42%) of the high-risk OPMDs. Moreover, among 88 high-risk OPMD patients with available follow-up results, 18 developed OSCC within 5 y; of them, 77.8% (14/18) had risk scores >0.4. Our four-protein panel may therefore offer a clinically effective tool for detecting OSCC and monitoring high-risk OPMDs through a readily available biofluid.
Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma, Squamous Cell/metabolism , Mouth Neoplasms/metabolism , Salivary Proteins and Peptides/metabolism , Carcinoma, Squamous Cell/pathology , Chromatography, Liquid , Demography , Early Detection of Cancer , Endoplasmic Reticulum Chaperone BiP , Female , Follow-Up Studies , Humans , Male , Mass Spectrometry , Middle Aged , Mouth Neoplasms/pathology , Neoplasm Staging , Risk Factors , Saliva/metabolism , TaiwanABSTRACT
PURPOSE: The study was undertaken to test whether human telomerase reverse transcriptase (hTERT) transcripts in an individual blastomere could be used as an indicator for embryo development. METHODS: Group A consisted of day 3 normal cleaving embryos at 4- to 8-cell stage, which were surplus and not allocated for uterine transfer. Group B consisted of arrested or fragmented embryos at the same stage, which were considered to be compromised. After blastomere dissociation, RNA purification, reverse transcription, and hTERT PCR amplification, the amplified product was separated by 3% gel electrophoresis. RESULTS: Eighty-six (90.5%) of the 95 intact blastomeres in group A and 78 (70.9%) of the 110 blastomeres in group B demonstrated hTERT mRNA expression. The difference was statistically significant (P < 0.05, chi-square). Eight (38.1%) of the 21 embryos in group A and 22 (62.9%) of the 35 embryos in group B had at least one blastomere that did not express hTERT mRNA under this procedure. The difference was not significant (P > 0.05, chi-square). CONCLUSIONS: General hTERT mRNA transcripts can be detected in most of the individual blastomeres but cannot be used as an indicator for early embryo development. Further investigations are necessary to elucidate its clinical application.
Subject(s)
Blastomeres/metabolism , Embryo, Mammalian/metabolism , Embryonic Development , Telomerase/biosynthesis , Blastomeres/ultrastructure , Cell Line, Tumor , Cell Survival , DNA, Complementary/metabolism , DNA-Binding Proteins , Embryo Implantation , Embryo Transfer , Female , Humans , Polymerase Chain Reaction/methods , RNA/metabolism , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Reverse Transcription , Telomerase/metabolism , Time Factors , Transcription, GeneticABSTRACT
BACKGROUND: We designed a self-sampling method to collect exfoliated genital cells for human papilloma virus (HPV) detection. The aim was to assess whether it was suitable as an assistant tool for the early detection of cervical pre-cancer and cancer in a special category of the women who are not frequently screened for cervical cancer. METHODS: We compared the results of HPV detection that were self-obtained and physician-obtained cervical swabs from the same patient that were analyzed using hybrid capture II assay. The diagnostic rate of cervical pre-cancer and cancer between self-obtained method and physician-obtained method were analyzed. RESULTS: A total of 1194 women were prospectively registered from September 1997 through September 1999. Among them, 144 (12.1%) of self-test samples and 155 (13%) of physician-obtained samples were oncogenetic associated-HPV positive. Statistically, no significant differences existed in the screening rate for cervical cancer using either the self-collected samples or the physician-obtained samples (p > .05). The sensitivity of cervical precancer or cancer detection using self-obtained HPV testing was higher (96.3%) as compared with the Pap smear (79.2%) (p < .02). CONCLUSION: The detection correlation of the HPV test between the self-obtained method and physician-obtained method was 93%. Our results indicated that self-sampling was a reliable method for testing for HPV. The identification of HPV infection through the self-obtained method can be used in early identification of high-risk women with cervical precancer and cancer especially in underserved populations.