ABSTRACT
MYC overexpression is considered a driver event in gastric cancer (GC), and is frequently correlated with poor prognosis and metastasis. In this study, we evaluated the prognostic value of genes upregulated by MYC in patients with GC. Metastatic GC cells (AGP01) characterized by MYC amplification, were transfected with siRNAs targeting MYC. RNA-seq was performed in silenced and non-silenced AGP01 cells. Among the differentially expressed genes, CIAPIN1, MTA2, and UXT were validated using qRT-PCR, western blot, and immunohistochemistry in gastric tissues of 213 patients with GC; and their expressions were correlated with clinicopathological and survival data. High mRNA and protein levels of CIAPIN1, MTA2, and UXT were strongly associated with advanced GC stages (P < 0.0001). However, only CIAPIN1 and UXT gene expressions were able to predict distant metastases in patients with early-stage GC (P < 0.0001), with high sensitivity (> 92%) and specificity (> 90%). Overall survival rate of patients with overexpressed CIAPIN1 or UXT was significantly lower (P < 0.0001). In conclusion, CIAPIN1 and UXT may serve as potential molecular markers for GC prognosis.
ABSTRACT
BACKGROUND: Anal residual tumors are consensually identified within six months of chemoradiotherapy and represent a persistent lesion that may have prognostic value for overall survival. The aim of this study was to evaluate the association of HPV and HIV status, p16 expression level and TP53 mutations with the absence of residual tumors (local response) in Squamous Cell Carcinoma (SCC) of the anal canal after chemoradiotherapy. METHODS: We performed a study on 78 patients with SCC of the anal canal who submitted to chemoradiotherapy and were followed for a six-month period to identify the absence or presence of residual tumors. HPV DNA was identified by polymerase chain reaction and direct sequencing, HIV RNA was detected by TaqMan amplification, p16 expression was detected by western blotting, and the mutational analysis of TP53 was performed by direct sequencing; additionally, samples carrying mutations underwent fluorescent in sit hybridization. The evaluation of the tumor response to treatment was conducted six months after the conclusion of chemoradiotherapy. The following classifications were used to evaluate the outcomes: a) no response (presence of residual tumor) and b) complete response (absence of residual tumor). RESULTS: The significant variables associated with the absence of residual tumors were HPV positive, p16 overexpressed, wild-type TP53, female gender, and stages I and II. Only the presence of HPV was independently correlated with the clinical response; this variable increased the chances of a response within six months by 31-fold. CONCLUSIONS: The presence of HPV in tumor cells was correlated with the absence of a residual tumor. This correlation is valuable and can direct future therapeutic approaches in the anal canal.
Subject(s)
Anus Neoplasms/therapy , Carcinoma, Squamous Cell/therapy , Chemoradiotherapy , DNA, Viral/analysis , Genes, p16 , Neoplasm, Residual , Papillomaviridae/genetics , Tumor Suppressor Protein p53/genetics , Adult , Aged , Aged, 80 and over , Anus Neoplasms/genetics , Anus Neoplasms/pathology , Anus Neoplasms/virology , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/virology , Female , Gene Expression , Genotype , HIV/genetics , Humans , Male , Middle Aged , Mutation , Neoplasm Staging , Treatment OutcomeABSTRACT
We develop a semiclassical theory to explain the rapid ripple fluctuations in the extinction efficiency of light scattering by a transparent prolate spheroid. The theory is based on uniform asymptotic expansion of spheroidal radial functions. We have calculated the extinction efficiency for normal and oblique incidence. Our results suggest that the excitation of resonant electromagnetic modes inside a spheroidal particle is an important factor in the ripple structure. To verify this assumption and based on a Breit-Wigner formula, we develop a method to fit the peaks that appear in the spheroid's extinction cross section when some scattering parameters vary. In other words, our calculations suggest that narrow resonances are related to ripple fluctuations, whereas broad resonances contribute to extinction cross-sectional background.
