Prognostic Factors and a Nomogram Predicting Survival in Patients with Breast Ductal Carcinoma in situ with Microinvasion: A Population-Based Study.

PURPOSE: Ductal carcinoma in situ with microinvasion (DCISM) can be challenging to balance the risks of overtreatment versus undertreatment. We aim to identify prognostic factors in patients with DCISM and construct a nomogram to predict breast cancer-specific survival (BCSS). MATERIALS AND METHODS: A retrospective cohort study of women diagnosed with DCISM from 1988 to 2015 who were identified in the Surveillance, Epidemiology and End Results database. Clinical variables and tumor characteristics were evaluated, and Cox proportional-hazards regression was performed. A nomogram was constructed from the multivariate logistic regression to combine all the prognostic factors to predict the prognosis of DCISM patients at 5 years, 10 years, and 15 years. RESULTS: We identified 5438 total eligible breast cancer patients with a median and max survival time of 78 and 227 months, respectively. Here, patients with poorer survival outcomes were those diagnosed between 1988 and 2001, African-American race, under 40 years of age, higher tumor N stage, progesterone receptor-negative tumor, and received no surgery. The nomogram was constructed by the seven variables and passed the calibration and validation steps. The area under the receiver operating characteristic (ROC) curve (AUC) of both the training set and the validating set (5-year AUC: 0.77 and 0.88, 10-year AUC: 0.75 and 0.73, 15-year AUC: 0.72 and 0.65). Receiving chemotherapy was associated with a better BCSS (hazard ratio, HR=0.45, 95% confidence interval, 95% CI = 0.23-0.89), especially in patients with estrogen receptor (ER) negative, progesterone receptor (PR) negative (HR = 0.35, 95% CI = 0.13-0.97) and ER+PR-/ER-PR+ DCISM (HR = 0.07, 95% CI = 0.01-0.59). CONCLUSION: Our current study is the first to construct nomograms of patients with DCISM which could help physicians identify breast cancer patients that more likely to benefit from more intensive treatment and follow-up. Chemotherapy might benefit patients with ER-PR- and ER+PR-/ER-PR+ DCISM.

Androgen receptor expression predicts different clinical outcomes for breast cancer patients stratified by hormone receptor status.

In this study we sought to correlate androgen receptor (AR) expression with tumor progression and disease-free survival (DFS) in breast cancer patients. We investigated AR expression in 450 breast cancer patients. We found that breast cancers expressing the estrogen receptor (ER) are more likely to co-express AR compared to ER-negative cancers (56.0% versus 28.1%, P < 0.001). In addition, we found that AR expression is correlated with increased DFS in patients with luminal breast cancer (P < 0.001), and decreased DFS in TNBC (triple negative breast cancer, P = 0.014). In addition, patients with HR+ tumors (Hormone receptor positive tumors) expressing low levels of AR have the lowest DFS among all receptor combinations. We also propose a novel prognostic model using AR receptor status, BRCA1, and present data showing that our model is more predictive of disease free survival compared to the traditional TMN staging system.

The phosphorylation-specific association of STMN1 with GRP78 promotes breast cancer metastasis.

Metastasis is a major cause of death in patients with breast cancer. Stathmin1 (STMN1) is a phosphoprotein associated with cancer metastasis. It exhibits a complicated phosphorylation pattern in response to various extracellular signals, but its signaling mechanism is poorly understood. In this study, we report that phosphorylation of STMN1 at Ser25 and Ser38 is necessary to maintain cell migration capabilities and is associated with shorter disease-free survival (DFS) in breast cancer. In addition, we report that glucose-regulated protein of molecular mass 78 (GRP78) is a novel phospho-STMN1 binding protein upon STMN1 Ser25/Ser38 phosphorylation. This phosphorylation-dependent interaction is regulated by MEK kinase and is required for STMN1-GRP78 complex stability and STMN1-mediated migration. We also propose a prognostic model based on phospho-STMN1 and GRP78 to assess metastatic risk in breast cancer patients.

[Mechanism of avian sex determination and differentiation].

Avian sex is determined by genes on the sex chromosomes (ZZ for male and ZW for female). In avian embryo stage, genes on one or two chromosomes control the sex differentiation. Gonad develops to testis in ZZ male and to ovary in ZW female. To date, DMRT1 (Doublesex and mab-3 related transcription factor 1) is considered to be the best candidate gene in controlling the avian gonad differentiation. However, recent study showed that avian sex might be determined by cell autonomous independent of sex hormone signal. Therefore, sex determination gene does not only control the gonadal differentiation, but also control body cells. From this sense, DMRT1 is not the switch gene of avian sex determination. What is the switch factor of avian sex determination, and what is the mechanism of avian sex determination? This review discussed the current progresses on avian sex determination and differentiation from three aspects: W chromosome and ovary development, Z chromosome and testis development, and avian sex determination and cell autonomous.

[cDNA cloning and protein structure analysis of growth hormone from Clarias lazera].

Total RNA was isolated from pituitary gland of Clarias lazera, and the cDNA encoding growth hormone (GH) protein was amplified and cloned by reverse transcription polymerase chain reaction (RT-PCR). The open reading frame (ORF) of cDNA is of 603 nt which encodes GH precursor consisted of a signal peptide with 22 amino acid residues and a mature peptide with 178 amino acid residues. Sequence alignment indicated that the amino acid sequence homology approached to 95.8% between C. lazera and other 6 species of Siluriforms catfish. Secondary structure assessment showed that the GH protein contained different structural regions of alpha-helix, beta-sheet, beta-turn and random coil, among which alpha-helix has main proportion. Antigenicity analysis indicates that there exist 4 domains in amino acid sequence where B cell dominant epitopes could form. Summarily, the structure characteristics of C. lazera GH should provide a great benefit in its modification into recombinant vaccine or monoclonal antibody for future application.

[Intraspecific DNA sequence polymorphism and genetic markers in the mitochondrial CO I gene from three populations of Macrobrachium rosenbergii].

The mitochondrial COI gene was PCR amplified and sequenced from 17 samples obtained from three populations of Macrobrachium rosenbergii (F1 of the Burma wildtype population, Jiangsu cultured population and F2 of the Guangxi breeding population). A 498-bp long partial gene segment was acquired and used to study the genetic diversity among the three populations. Results indicated that the COI gene locus was relatively more polymorphic in the F1 of Burma wildtype population, while the polymorphism in Jiangsu cultured population and Guangxi breeding population were very poor. A total of 10 polymorphic sites and 5 haplotypes were found in the sequences of the 17 samples. The average nucleotide divergence in the three populations was 0.88%0.07% and 0 respectively. The UPGMA phylogenetic tree suggested that F2 of the Guangxi breeding population and Jiangsu cultured population were closest genetically, and their haplotypes could be gathered together to a genetic branch while F1 of the Burma wildtype population diverged and could form another relatively independent branch. For these distinct nucleotide differences, COI gene could be suitable as a genetic marker for distinguishing these two branches of the Macrobrachium rosenbergii population.