RESUMO
Kidney renal clear cell carcinoma (KIRC) is one of the most common cancers with high mortality worldwide. As members of the homeobox (HOX) family, homeobox-A (HOXA) genes have been reported to play an increasingly important role in tumorigenesis and the progression of multiple cancers. However, limited studies have investigated the potential diagnostic and prognostic roles of HOXA genes in KIRC. In this research, we explored the expression pattern of the HOXA gene family in KIRC progression by differential analysis of expression profiles from The Cancer Genome Atlas (TCGA). By using univariate Cox analysis and lasso regression analysis, we comprehensively evaluated the prognostic value of HOXA genes and eventually identified a prognostic risk model consisting of five HOXA genes (HOXA2, HOXA3, HOXA7, HOXA11, and HOXA13). The risk model was further validated as a novel independent prognostic factor for KIRC patients based on the calculated risk score by Kaplan-Meier analysis, univariate and multivariate Cox regression analyses, and time-dependent receiver operating characteristic (ROC) curve analysis. Moreover, to explore the potential mechanism of tumorigenesis and clinical application of KIRC, we also developed the HOXA-based competing endogenous RNA (ceRNA) regulatory network and machine learning classification model. Valproic acid and tretinoin were predicted to be the most promising small molecules to adjuvant treatment of KIRC by mining the CMAP and DGIdb drug database. Subsequently, pathway and functional enrichment analyses provided us with new ways to search for a possible mechanism of action of drugs. Taken together, our study demonstrated the nonnegligible role of HOXA genes in KIRC and constructed an effective prognostic and diagnostic model, which offers novel insights into KIRC prognosis.
RESUMO
BACKGROUND We aimed to explore the correlation between patients' sigmoid sinusoidal tinnitus (SST) and low-frequency sensorineural hearing loss (LFSHL) and illustrate the underlying mechanism. MATERIAL AND METHODS Seven healthy volunteers with normal hearing were subjected to 125-, 250-, and 500-Hz pure sound and different white noise-masking intensities. A retrospective analysis was made on the clinical data and postoperative follow-up data of 59 patients with SST in the First Affiliated Hospital of Chongqing Medical University. The patients' sex, age, chief complaints, affected site, concomitant symptoms, course of disease, pure-tone audiometry (PTA) results, tinnitus discomfort loudness scale results, imaging examination, and complications were collected. RESULTS The results of the simulation experiment showed that the threshold of each frequency segment was higher after noise masking than before masking; the intensity of noise masking was positively correlated with hearing loss, and the changes of the hearing threshold of the 3 frequencies before and after masking were statistically significant (P<0.05). Fifty-nine patients with SST were documented between January 2015 and January 2020. After the operation, their low-frequency hearing was recovered to normal; 11 cases had significantly alleviated tinnitus and 9 cases were cured. CONCLUSIONS SST often causes corresponding pseudo-low-frequency hearing loss due to the noise-masking effect. The center frequency of tinnitus appears not to be 250-Hz or 500-Hz octave frequency of PTA, barring the detection of the pseudo-hearing loss in the audiometry chart of most patients. Surgery positively affects patients with SST, and the pseudo-LFSHL can be completely recovered after the operation as a result of tinnitus elimination.
