Integrin-associated protein (CD47) is ubiquitously expressed on the surface of cells and functions as an identifier of self. In blood cancer, tumor cells expressing CD47 evade phagocytosis by ...macrophages, leading to a poor patient prognosis. However, the status of CD47 expression in solid tumors, particularly in gastric cancer, is not well understood. The purpose of the present study was to examine the level of CD47 in the primary tumor, peripheral blood (PB) and bone marrow (BM) of patients with gastric cancer, and to determine its effect. Reverse transcription-quantitative polymerase chain reaction analysis was performed to determine the level of CD47 mRNA expression in primary tumor, PB and BM samples collected from 168 patients with gastric cancer. Cell sorting was performed to investigate CD47 protein expression in PB and BM fractions, and to identify the source of CD47 expression. In primary tumors, the expression of CD47 was not associated with any clinicopathological factors or prognosis. By contrast, in PB, the low CD47 expression group demonstrated a significantly increased tumor size, and frequency of lymphatic invasion and lymph node metastasis, compared with the high CD47 expression group. In addition, the clinical tumor stage of the low CD47 expression group was significantly increased compared with that of the high CD47 expression group. Conversely, in PB, the high CD47 expression group had a significantly higher frequency of lymphatic invasion and lymph node metastasis compared with the low CD47 expression group. The lymphocyte fraction exhibited the highest CD47 expression compared with the other fractions in PB and BM samples. Low expression of CD47 was associated with the advancement of gastric cancer, in contrast to other cancers, and it may be associated with a decrease in lymphocytes during later stages. These results indicate that CD47 expression in the PB and BM may serve as a marker to analyze the immunological function of patients with gastric cancer; however, the significance of CD47 in gastric cancer requires further study.
Abstract
Objective
En bloc and margin-negative surgical resection seems to offer the best prognosis for patients with temporal bone squamous cell carcinoma (TB-SCC). In this study, we summarize the ...outcomes of surgical cases of advanced TB-SCC (T3–T4) that were managed in two institutions, with an accompanying description of the surgical procedure that was utilized: modified subtotal temporal bone resection (STBR), which involves the en bloc removal of the temporal bone including or transecting the otic capsule.
Design
This is a case series study with chart review.
Setting
The study was conducted at two academic tertiary care medical centers.
Participants
Chart information was collected for all patients who underwent surgical resection of advanced TB-SCC between July 1998 and February 2019. The resulting dataset contained 43 patients with advanced TB-SCC who underwent en bloc resection during the review period. Tumor staging followed the modified Pittsburgh classification. Disease-specific survival (DSS) rates were calculated according to the Kaplan–Meier method.
Main Outcome Measure
This study shows disease-specific 5-year DSS rate.
Results
The 5-year DSS rate of the cases who underwent en bloc resection was 79.7%. En bloc lateral temporal bone resection was employed in a total of 25 cases (DSS: 79.0%). En bloc modified STBR was utilized in 18 cases (DSS: 81.7%).
Conclusion
En bloc margin-negative resection is a reliable treatment strategy for advanced TB-SCC. Modified STBR can be a treatment option for TB-SCC without marked posterior extension.
The involvement of epithelial-mesenchymal transition (EMT) in esophageal squamous cell carcinoma (ESCC) has not been fully elucidated. Here, we aimed to identify EMT-related genes associated with ...TGF-β in ESCC and to clarify the role of these genes in the progression of ESCC.
EMT-related genes associated with TGF-β expression were identified in patients with ESCC using microarray analysis and public datasets. The effects of ubiquitin-like with PHD and ring finger domains 2 (UHRF2) expression were analyzed in ESCC cell lines. Cell proliferation and invasion were measured using MTT and invasion assays, respectively. UHRF2 mRNA expression was also analyzed in 75 ESCC specimens to determine the clinical significance of UHRF2 in ESCC.
Treatment of ESCC cell lines with TGF-β increased UHRF2 expression. UHRF2 overexpression increased CDH1 (E-cadherin) expression and decreased invasive capacity. The 75 ESCC specimens were divided into the UHRF2 high-expression group (n = 61) and the UHRF2 low-expression group (n = 14). Low UHRF2 expression was significantly correlated with vascular invasion (p = 0.034) and was an independent prognostic factor for poor prognosis (p = 0.005).
UHRF2 may be a negative regulator of EMT and a novel prognostic biomarker for ESCC.
Objective:
The extreme rarity of temporal bone squamous cell carcinoma (TB-SCC) has delayed the accumulation of high-quality clinical evidence. Our objective here was to explore anatomical factors ...associated with the prognosis of T4 TB-SCC cases.
Study Design:
Case series with chart review.
Setting:
Two academic tertiary care medical centers.
Subjects and Methods:
The medical records of all TB-SCC cases were retrospectively reviewed in two institutions. The resulting data set contained 30 cases of primary T4 cancer eligible for initial definitive (curative) treatment. Disease-specific survival was calculated according to the Kaplan–Meier method. Cox proportional hazards model was used to identify anatomical prognosis factors.
Results:
The disease-specific 5-years survival rate of 30 cases of T4 TB-SCC was 53.9%. The tumor invasion to the pterygoid muscle, posterior fossa dura, and sigmoid sinus and destruction of the ossicles were associated with poor prognosis in univariate analysis. The multivariate analysis reveals that the invasion of the ossicles, posterior fossa dura, and sigmoid sinus is an independent prognostic factor hazard ratio (HR): 4.528 (95% CI: 1.161–17.658), p = 0.030; HR: 5.135 (95% CI: 1.616–16.315), p = 0.006; HR: 4.292 (95% CI: 1.385–13.303), p = 0.012. The invasion of the carotid canal, petrous apex, middle fossa dura, otic capsule, pterygoid muscle, and middle ear had a high HR (HR > 2). The more invaded anatomical factors present in patients resulted in a poorer patient disease-specific prognosis, with a statistically significant difference.
Conclusions:
Assessing which anatomical structures are susceptible to invasion by tumors may be important for predicting TB-SCC patient prognosis and selecting appropriate treatment planning, especially surgical intervention. In addition to previously reported factors, the destruction of the ossicles in the middle ear cavity can be an anatomical prognosis factor.
SLC9A9 plays an oncogenic role in esophageal squamous carcinoma and glioblastoma. Herein, we showed an oncogenic function of SLC9A9 in colorectal cancer (CRC).
We examined SLC9A9 expression in CRC ...specimens by immunohistochemistry. In CRC tissues, the relationship between SLC9A9 expression and clinicopathological factors was further elucidated by quantitative real-time polymerase chain reaction (qRT-PCR) and gene set enrichment analysis (GSEA). In vitro, we performed knockdown and overexpression experiments.
SLC9A9 was overexpressed in CRC specimens. In clinicopathological analysis of our cohort, high SLC9A9 expression increased liver metastasis and was correlated with worse prognoses in two cohorts. A significantly positive relationship between SLC9A9 and EGFR was revealed. While knockdown of SLC9A9 suppressed proliferation and anchorage-independent growth, up-regulation of SLC9A9 promoted proliferation and anchorage-independent growth in vitro.
SLC9A9 has an oncogenic function by being related to EGFR signaling, suggesting SLC9A9 may be a novel prognostic indicator and a therapeutic target in CRC.
Primary auditory neurons (PANs) play a critical role in hearing by transmitting sound information from the inner ear to the brain. Their progressive degeneration is associated with excessive noise, ...disease and aging. The loss of PANs leads to permanent hearing impairment since they are incapable of regenerating. Spiral ganglion non-neuronal cells (SGNNCs), comprised mainly of glia, are resident within the modiolus and continue to survive after PAN loss. These attributes make SGNNCs an excellent target for replacing damaged PANs through cellular reprogramming. We used the neurogenic pioneer transcription factor Ascl1 and the auditory neuron differentiation factor NeuroD1 to reprogram SGNNCs into induced neurons (iNs). The overexpression of both
and
generated iNs at high efficiency. Transcriptome analyses revealed that iNs displayed a transcriptome profile resembling that of endogenous PANs, including expression of several key markers of neuronal identity: Tubb3, Map2, Prph, Snap25, and Prox1. Pathway analyses indicated that essential pathways in neuronal growth and maturation were activated in cells upon neuronal induction. Furthermore, iNs extended projections toward cochlear hair cells and cochlear nucleus neurons when cultured with each respective tissue. Taken together, our study demonstrates that PAN-like neurons can be generated from endogenous SGNNCs. This work suggests that gene therapy can be a viable strategy to treat sensorineural hearing loss caused by degeneration of PANs.
There are no human cancer cell lines of external auditory canal origin available for research use. This report describes the establishment of a culture condition for external auditory canal squamous ...cell carcinoma, derived from human tumor tissue. Successive squamous cell carcinoma colonies were dissociated by trypsin, subcultured, and maintained on a feeder layer (MMC‐TIG‐1‐20), yielding a clonally proliferating cell culture. Two morphological types of colony were observed: (a) densely packed colonies and (b) colonies with indistinct boundaries characterized by cell–cell complexes with fibroblast feeder cells. The SCC‐like characteristics of these cells were evidenced by positivity for p53, SCCA1/2, cytokeratin, and vimentin, and cancer stem cell properties were indicated by positivity for CD44, CD133, Oct3/4, and alkaline phosphatase (ALP). One of the unique properties of cell cultures is their tendency to form steric colonies in vitro on feeder layer cells. In addition, in the presence of fresh macrophages, the cells very slowly transform to break away from colonies as free cells, a process that resembles the epidermal–mesenchymal transition, whereby cell–cell interactions are weakened and migration activity is enhanced. These factors are purported to play a key role in cancer cell metastasis.
No human cancer cell lines of external auditory canal (EAC) origin are available for research use. This report describes the establishment of a culture condition for EAC squamous cell carcinoma (SCC). These cell cultures had cancer stem cell properties and tended to form steric colonies on feeder cells. These cell cultures could be used in future research on EAC‐SCC.
Few driver genes have been well established in esophageal squamous cell carcinoma (ESCC). Identification of the genomic aberrations that contribute to changes in gene expression profiles can be used ...to predict driver genes.
We searched for driver genes in ESCC by integrative analysis of gene expression microarray profiles and copy number data. To narrow down candidate genes, we performed survival analysis on expression data and tested the genetic vulnerability of each genes using public RNAi screening data. We confirmed the results by performing RNAi experiments and evaluating the clinical relevance of candidate genes in an independent ESCC cohort.
We found 10 significantly recurrent copy number alterations accompanying gene expression changes, including loci 11q13.2, 7p11.2, 3q26.33, and 17q12, which harbored CCND1, EGFR, SOX2, and ERBB2, respectively. Analysis of survival data and RNAi screening data suggested that GRB7, located on 17q12, was a driver gene in ESCC. In ESCC cell lines harboring 17q12 amplification, knockdown of GRB7 reduced the proliferation, migration, and invasion capacities of cells. Moreover, siRNA targeting GRB7 had a synergistic inhibitory effect when combined with trastuzumab, an anti-ERBB2 antibody. Survival analysis of the independent cohort also showed that high GRB7 expression was associated with poor prognosis in ESCC.
Our integrative analysis provided important insights into ESCC pathogenesis. We identified GRB7 as a novel ESCC driver gene and potential new therapeutic target.
Purpose
Recent studies indicated that the scaffolding adaptor protein GAB2 (GRB2-associated binding protein 2) plays a critical role in the proliferation and migration of various cancers. This study ...aimed to determine the role of aberrant
GAB2
expression in human colorectal cancer (CRC).
Methods
Quantitative real-time reverse transcription polymerase chain reaction was used to evaluate
GAB2
mRNA expression in 152 CRC tissues samples to determine the clinicopathological significance of
GAB2
expression. We also performed in vitro proliferation assays using si
GAB2
-transfected CRC cells.
Results
GAB2
expression in tumor colorectal tissues was significantly higher than in normal colorectal tissues (
p
= 0.0212). High
GAB2
expression levels were associated with malignant clinicopathologic potential factors, including lymphatic invasion (
p
= 0.0003), venous invasion (
p
= 0.0170), and liver metastasis (
p
= 0.0144). The survival rate of patients with high
GAB2
expression levels was significantly lower than that of patients with low
GAB2
expression (
p
= 0.0074). Multivariate analysis indicated that
GAB2
expression was a factor affecting lymph node metastasis. Cell proliferation was significantly suppressed by si
GAB2
expression in CRC cells in vitro.
Conclusions
GAB2
expression was associated with lymph node metastasis and may play a role in the growth and metastasis of CRC. These results suggest that
GAB2
is a potential therapeutic target in CRC.
Background
Here, we explored the genetic interactions between diabetes and oncogenic single-nucleotide polymorphisms (SNPs) that determine colorectal cancer (CRC) morbidity.
Methods
8q24 rs6983267 ...polymorphism analysis and cDNA microarray were performed in 107 CRCs to identify the genes associated with diabetes and the oncogenic SNP. Then clinical significance of the gene was validated in 132 CRCs. Meta-analysis of microarray data and diabetic comorbidity was performed.
Results
Of genes associated with a minor SNP allele at 8q24, diabetes, and
MYC
overexpression, apolipoprotein A-IV (
ApoA
-
IV
) was associated with oncogenesis and poor prognosis in CRC patients. Patients with high
ApoA
-
IV
expression showed significantly poorer prognosis by univariate and multivariate analysis. Meta-analysis revealed lipid metabolism was associated with ApoA-IV-related oncogenesis in diabetic patients.
Conclusions
Changes in lipid metabolism associated with aberrant expression of
ApoA
-
IV
were risks for CRC oncogenesis.
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