Background The incidence of papillary thyroid cancer (PTC) has increased rapidly in recent decades, and tumor progression events are common in PTC. The purpose of our study is to identify the differentially expressed genes (DEGs) correlated with PTC progression and investigate the function of PDZK1IP1 in PTC. Methods We first analyzed DEGs associated with PTC progression between paired PTC and normal thyroid tissues in three GEO datasets (GSE29265, GSE33630 and GSE60542) and TCGA database. Data from TCGA database and our institution were utilized to explore the relationship between PDZK1IP1 expression and clinicopathological characteristics of PTC. The CCK8 cell proliferation assay, clone formation assay, flow cytometry assay and the xenograft model were used to investigate the function of PDZK1IP1 in PTC. Results 39 DEGs associated with PTC progression were identified, in which only PDZK1IP1 was upregulated in PTC tissue at both mRNA and protein levels. Besides, we found that high expression of PDZK1IP1 in TCGA database was associated with poor progression-free survival, extrathyroidal extension, high stage, tall cell variant and BRAF V600E mutation of the PTC (P<0.001). In our collected samples, high expression of PDZK1IP1 was only related to lymph node metastasis (P<0.05). Overexpression of PDZK1IP1 significantly promoted proliferation and inhibited apoptosis of PTC cells. Knockdown of PDZK1IP1 significantly inhibited proliferation, promoted apoptosis, and prevented xenograft formation of PTC cells. Conclusion PDZK1IP1 is an oncogene for tumorigenesis and development of PTC and might be a potential therapeutic target.
Purpose Microcalcification (MC) is a valuable diagnostic indicator to detect invasive breast cancer (IBC). This study aimed to determine the clinicopathological features of IBC with MC and detect biomarkers related to the potential mechanism of the MC formation in IBC. Methods Data from 364 patients with IBC were collected for the clinical characteristic analysis. The analysis of clinical data helped us to establish a predictive model of axillary node metastasis (ANM) before surgery. In addition, 49 tissue samples of IBC patients were collected to test the protein levels of osteocalcin (OCN) and hypoxia‐inducible factor‐1α (HIF‐1α) by immunohistochemistry. Results Significant differences were observed in tumor size, age, ANM, HER2+, TNM stage, and mutant P53 between samples from IBC patients with MC and samples from IBC patients without MC. Younger age, a larger tumor size, a higher number of childbirths, and MC were independent predictors for ANM in IBC. HIF‐1α protein level was higher in tumor tissue than in normal tissue. High protein levels of OCN and HIF‐1α are related to the complication of MC in IBC. Of the patients that exhibited high HIF‐1α protein levels, the percentage of high OCN protein levels was larger in patients with ANM. Conclusion Based on this study, we concluded that patients with MC had a comparatively poor prognosis. MC was an independent predictive factor associated with the risk of ANM. High protein levels of OCN and HIF‐1α were associated with MC and ANM, which were also related to poor prognosis. OCN and HIF‐1α had a positive correlation in IBC.
Background Intraductal papillary carcinoma (IPC) with invasion is a rare type of breast cancer. There have been few studies on its prognosis, and a nomogram that predicts the prognosis of the disease has not been described to date. Methods Patients who were diagnosed with invasive IPC were screened from the Surveillance, Epidemiology, and End Results (SEER) database. The screened patients were randomly divided into a training cohort and a verification cohort at 7:3. A Cox proportional hazard regression model was performed to analyze the effects of different variables on the risk of death in invasive IPC. A nomogram was constructed to quantify the possibility of death. The concordance index (C‐index), calibration plots, receiver operating characteristic (ROC) curves, and decision curves analysis (DCA) were used to verify the proposed model. Results We included a total of 803 patients diagnosed with invasive IPC, including 563 patients in the training cohort and 240 patients in the validation cohort. The median follow‐up times in the training cohort and validation cohort were 63 months (range, 2–155 months) and 61 months (range, 1–154 months), respectively. For all patients, the probability of death with invasive IPC was 1.4% within 5 years and 5.4% within 10 years. In multivariate analysis, sex, race, tumor size, lymph node status, type of treatment, and chemotherapy were related to the prognosis of invasive IPC. We constructed a nomogram to predict the possibility of death in patients with invasive IPC. Conclusion Patients with invasive IPC had a high survival rate. The proven nomogram was helpful to both patients and clinical decision makers.
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