Overexpression of LAG3, TIM3, and A2aR in adenoid cystic carcinoma and mucoepidermoid carcinoma.

OBJECTIVE: Adenoid cystic carcinoma (AdCC) and mucoepidermoid carcinoma (MEC) are the two most frequent malignancies of salivary glands. This study aims to explore the expression and migration of LAG3, TIM3, and A2aR in AdCC and MEC, and the potential relationship with oncogenic signaling molecules and immunosuppressive cytokines. MATERIALS AND METHODS: Custom made human salivary gland tissue microarrays included 81 AdCCs, 52 MECs, 76 normal salivary glands (NSG), and 14 pleomorphic adenoma (PMA) samples. Immunohistochemical analysis of lymphocyte activation gene 3 (LAG3), T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3), adenosine 2a receptor (A2aR), oncogenic phosphorylated S6 kinase (p-S6) and ERK1/2 (p-ERK1/2 ), and TGF-ß1 was performed with salivary gland tissue microarrays of human samples. The correlation of the immunostaining was analyzed based on a digital pathological system, and data were evaluated by hierarchical cluster. Further in vitro studies of knockdown immune checkpoints LAG3, TIM3, and A2aR were carried out by siRNA transfection. RESULTS: The expression levels of LAG3, TIM3, and A2aR were remarkably increased in AdCC and MEC, compared with NSG and PMA samples, but were independent of pathology grade. They were closely correlated with TGF-ß1, slightly related to p-ERK1/2 and p-S6. After the knockdown of immune checkpoints LAG3, TIM3, and A2aR, the migration of SACC-LM cell line was significantly reduced. CONCLUSIONS: These results suggested that LAG3, TIM3, and A2aR are overexpressed in AdCC and MEC, may promote migration of SACC-LM cell and correlated with TGF-ß1 and oncogenic signaling pathways.

Sequential damage assessment of the posterolateral complex of the knee joint: a finite element study.

BACKGROUND: The posterolateral complex (PLC), which consists of the popliteus tendon (PT), lateral collateral ligament (LCL), and popliteofibular ligament (PFL), is an indispensable structure of the knee joint. The aim of this study was to explore the functionality of the PLC by determining the specific role of each component in maintaining posterolateral knee stability. METHODS: A finite element (FE) model was generated based on previous material property data and magnetic resonance imaging of a volunteer's knee joint. The injury order of the PLC was set as LCL, PFL, and PT. A combined compressive load of 1150 N and an anterior tibial load of 134 N was applied to the tibia to investigate tibial displacement (TD). Tibial external rotation (TER) and tibial varus angulation (TVA) were measured under bending motions of 5 and 10 Nm. The instantaneous axis of rotation (IAR) of the knee joint under different rotation motions was also recorded. RESULTS: The TD of the intact knee under a combined compressive load of 1150 N and an anterior tibial load of 134 N matched the values determined in previous studies. Our model showed consistent increases in TD, TVA, and TER after sequential damage of the PLC. In addition, sequential disruption caused the IAR to shift superiorly and laterally during varus rotation and medially and anteriorly during external rotation. In the dynamic damage of the PLC, LCL injury had the largest effect on TD, TVA, TER, and IAR. CONCLUSIONS: Sequential injury of the PLC caused considerable loss of stability of the knee joint according to an FE model. The most significant structure of the PLC was the LCL.

Expression of HHLA2, TMIGD2, and GITR in salivary gland adenoid cystic carcinoma and mucoepidermoid carcinoma.

BACKGROUND: Mucoepidermoid carcinoma and adenoid cystic carcinoma are the two most common malignancies of salivary gland. Our study aims to explore the role of human endogenous Retrovirus-H long terminal repeat-associating protein 2, transmembrane and immunoglobulin domain-containing 2, and glucocorticoid-induced tumor necrosis factor receptor in adenoid cystic carcinoma and mucoepidermoid carcinoma, and the relationship between human endogenous Retrovirus-H long terminal repeat-associating protein 2, transmembrane and immunoglobulin domain-containing 2, glucocorticoid-induced TNF receptor, oncogenic signaling molecules, and cluster of differentiation 8. METHODS: Custom-made human salivary gland tissue microarrays included 81 Adenoid cystic carcinoma, 52 mucoepidermoid carcinoma, 76 normal salivary gland, and 14 pleomorphic adenoma samples. Immunohistochemical analysis of human endogenous Retrovirus-H long terminal repeat-associating protein 2, transmembrane and immunoglobulin domain-containing 2, and glucocorticoid-induced TNF receptor, oncogenic phosphorylated Erk1/2 , the epithelial-mesenchymal transition (EMT) molecule transforming growth factor ß1, and cluster of differentiation 8 was performed with salivary gland tissue microarray of human samples. RESULTS: According to a digital pathological system, we analyzed the correlation of immunostaining. The expression levels of human endogenous Retrovirus-H long terminal repeat-associating protein 2, transmembrane and immunoglobulin domain-containing 2, and glucocorticoid-induced TNF receptor were significantly enhanced in the adenoid cystic carcinoma and mucoepidermoid carcinoma, compared with those of pleomorphic adenoma and NSG samples. However, the expression levels of human endogenous Retrovirus-H long terminal repeat-associating protein 2, transmembrane and immunoglobulin domain-containing 2, and glucocorticoid-induced TNF receptor were independent of the pathological grade of malignancy of mucoepidermoid carcinoma and histological pattern of adenoid cystic carcinoma. They were closely related to phosphorylated Erk1/2 and transforming growth factor ß1, but negligibly related to cluster of differentiation 8. CONCLUSIONS: These results described that certain immune checkpoint molecules, namely, human endogenous Retrovirus-H long terminal repeat-associating protein 2, transmembrane and immunoglobulin domain-containing 2, and glucocorticoid-induced TNF receptor were overexpressed in Adenoid cystic carcinoma and mucoepidermoid carcinoma, but were independent of pathological grade, and may relate to transforming growth factor ß1, phosphorylated Erk1/2, and cluster of differentiation 8.

Biomaterial-mediated modulation of oral microbiota synergizes with PD-1 blockade in mice with oral squamous cell carcinoma.

Because a host's immune system is affected by host-microbiota interactions, means of modulating the microbiota could be leveraged to augment the effectiveness of cancer therapies. Here we report that patients with oral squamous cell carcinoma (OSCC) whose tumours contained higher levels of bacteria of the genus Peptostreptococcus had higher probability of long-term survival. We then show that in mice with murine OSCC tumours injected with oral microbiota from patients with OSCCs, antitumour responses were enhanced by the subcutaneous delivery of an adhesive hydrogel incorporating silver nanoparticles (which inhibited the growth of bacteria competing with Peptostreptococcus) alongside the intratumoural delivery of the bacterium P. anaerobius (which upregulated the levels of Peptostreptococcus). We also show that in mice with subcutaneous or orthotopic murine OSCC tumours, combination therapy with the two components (nanoparticle-incorporating hydrogel and exogenous P. anaerobius) synergized with checkpoint inhibition with programmed death-1. Our findings suggest that biomaterials can be designed to modulate human microbiota to augment antitumour immune responses.

Total hip revision with custom-made spacer and prosthesis: A case report.

BACKGROUND: Both periprosthetic joint infections (PJIs) and severe femoral segmental defects are catastrophic complications of total hip arthroplasty (THA), and both present a significant challenge in revisional surgery. There are limited data available to guide clinical decision making when both occur concurrently. CASE SUMMARY: A 61-year-old woman presented with a 6-mo history of a sinus tract at the site of her original THA incision. Radiological imaging revealed a total hip joint implant with an ipsilateral segmental femoral defect. Based on histological, radiological, laboratory, and clinical features, a diagnosis of concurrent chronic PJI and segmental femoral defect (Type IIIB, Paprosky classification) was made. After multidisciplinary team discussion, three-dimensional (3D)-printed, custom-made antibiotic spacers were created that could be used to mold antibiotic-loaded cement spacer. These were placed following PJI debridement in the first stage of revision surgery. After the PJI was eliminated, a 3D-printed, custom-made, femoral prosthesis was created to repair the considerable femoral defect. After 20-mo follow-up, the patient had excellent functional outcomes with a near-normal range of hip movement. So far, neither evidence of recurrent infection nor loosening of the prosthesis has been observed. CONCLUSION: We describe a case of "two-stage, custom-made" total hip revision to treat PJI with a concurrent segmental femoral defect. Use of a personalized, 3D-printed spacer and proximal femoral prosthesis led to satisfactory hip function and no early postoperative complications. Use of a customized implant provides surgeons with an alternative option for patients where no suitable spacer or implant is available. However, the long-term function, longevity, and cost-effectiveness of the use of custom-made prostheses have yet to be fully explored.

Non-depleting reformation of immunosuppressive myeloid cells to broaden the application of anti-PD therapy.

Traditional methods of depleting tumor-associated myeloid cells via chemotherapy can easily lead to the re-recruitment of them, eventually resulting in chemo-resistance and presenting obstacles in immunotherapy. Herein, we report a nano-educator (NE) that when loaded with all trans retinoic acid (ATRA) and anti-PD-1 antibodies (aPD-1) instructs myeloid cells to assist T cells towards revitalizing anti-PD-1 therapy. In vivo, ATRA converts myeloid-derived suppressor cells (MDSCs) into dendritic cells (DCs), which are essential for anti-PD-1 therapy, while intervening in the polarization of macrophages. Furthermore, aPD-1-armed T cells reboot anti-tumor immunity after suppression relief, which exposes tumor-specific antigens and in turn promotes the maturation of transformed DCs. The nano-platform provides shelter for vulnerable immunomodulatory agents and durable drug release to stimulate intensive immune modulation. We established three types of tumor-bearing mice models with different myeloid cell contents to show the spatiotemporal complementarity of ATRA and aPD-1. The NE re-educates the tumor's guard to assist T cells in enhanced immunotherapy, broadening the application of aPD-1 in the treatment of anti-PD-1-resistant tumors.

The role of MYB proto-oncogene like 2 in tamoxifen resistance in breast cancer.

Despite the efficacy of tamoxifen in preventing disease relapse, a large portion of breast cancer patients show intrinsic or acquired resistance to tamoxifen, leading to treatment failure and unfavorable clinical outcome. MYB proto-oncogene like 2 (MYBL2) is a transcription factor implicated in the initiation and progression of various human cancers. However, its role in tamoxifen resistance in breast cancer remained largely unknown. In the present study, by analyzing public transcriptome dataset, we found that MYBL2 is overexpressed in breast cancer and is associated with the poor prognosis of breast cancer patients. By establishing tamoxifen-resistant breast cancer cell lines, we also provided evidence that MYBL2 overexpression contributes to tamoxifen resistance by up-regulating its downstream transcriptional effectors involved in cell proliferation (PLK1, PRC1), survival (BIRC5) and metastasis (HMMR). In contrast, inhibiting those genes via MYBL2 depletion suppresses cancer progression, restores tamoxifen and eventually reduces the risk of disease recurrence. All these findings revealed a critical role of MYBL2 in promoting tamoxifen resistance and exacerbating the progression of breast cancer, which may serve as a novel therapeutic target to overcome drug resistance and improve the prognosis of breast cancer patients.

Periodontal Disease and Tooth Loss Are Associated with Lung Cancer Risk.

BACKGROUND: The associations between periodontal disease, tooth loss, and lung cancer risk remain debatable. Therefore, the purpose of the present study is to evaluate whether periodontal disease and tooth loss are associated with lung cancer risk. METHODS: A literature search was performed for relevant studies using PubMed and Embase databases. Risk ratio (RR) with 95% confidence interval (CI) was applied as effect size to summarize the associations between periodontal disease, tooth loss, and lung cancer risk. A further dose-response analysis was also performed. RESULTS: A total of twelve studies comprising 263,238 participants were included. The results indicated that periodontal disease was positively associated with lung cancer risk (RR = 1.37, 95%CI = 1.16-1.63). There was a positive association between tooth loss and lung cancer risk (RR = 1.69, 95%CI = 1.46-1.96). Moreover, there was a significantly linear dose-response relationship between tooth loss and lung cancer risk, and every 5 increment in tooth loss was associated with 10% increased lung cancer risk. Similar results were obtained in subgroup analysis. CONCLUSIONS: Periodontal disease and tooth loss are increased risk factors for lung cancer. Prevention and treatment of periodontal disease may be effective potential prevention strategies for lung cancer.

Overexpression of PREX1 in oral squamous cell carcinoma indicates poor prognosis.

Phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger (P-Rex) proteins control many fundamental cellular functions including cell migration, actin cytoskeletal rearrangement and adhesion in many cancers. However, P-Rex1 expression and its prognostic effect and possible clinical value are not clearly elucidated in human oral squamous cell carcinoma (OSCC). Here, OSCC tissue microarrays were used to verify the expression levels of P-Rex1, coinhibitory immune checkpoints and tumor associated macrophage (TAM) markers, and to analyze the relationship between PREX1 expression levels and clinicopathological characteristics in OSCC. The study found that P-Rex1 expression was elevated in OSCC compared to dysplasia and normal mucosa (P < 0.0001). In addition, patients who expressed high PREX1 had a poorer prognosis than those who expressed low PREX1 (P = 0.0070). Furthermore, positive correlations were found between P-Rex1 expression and the immune checkpoints PD-L1, Galectin-9 and B7-H4, and the TAM markers CD68, CD206 and CD163. In short, these findings implicated that overexpression of P-Rex1 may predict a poor prognosis in human OSCC.

Association between periodontal disease, tooth loss and liver diseases risk.

AIM: The purpose of this study is to assess the associations between periodontal disease, tooth loss and liver diseases. MATERIALS AND METHODS: PubMed and Embase databases were utilized to search eligible studies. Odds ratio (OR) with 95% confidence interval (CI) was used as effect size to assess the associations between periodontal disease, tooth loss and liver diseases risk. RESULTS: Our results indicated positive associations between periodontal disease and non-alcoholic fatty liver disease (NAFLD) (OR = 1.19, 95% CI = 1.06-1.33), liver cirrhosis (OR = 2.28, 95% CI = 1.50-3.48) and elevated transaminase level risk (OR = 1.08, 95% CI = 1.02-1.15). Moreover, tooth loss could increase NAFLD (OR = 1.33, 95% CI = 1.12- 1.56) and liver cancer risk (OR = 1.34, 95% CI = 1.04-1.74), and every five increment in tooth loss was associated with 5% increased liver cancer risk (OR = 1.05, 95% CI = 1.01 - 1.10) with a linear relationship. In addition, tooth loss had a positive tendency towards liver cirrhosis risk (OR = 2.03, 95% CI = 0.85-4.85) although there was no statistical significance. CONCLUSION: Periodontal disease and tooth loss are positively associated with liver diseases including NAFLD, elevated transaminase level, liver cirrhosis and liver cancer.

Expression levels of SIX1, ME2, and AP2M1 in adenoid cystic carcinoma and mucoepidermoid carcinoma.

OBJECTIVE: Adenoid cystic carcinoma (AdCC) and mucoepidermoid carcinoma (MEC) are the most frequent malignancies in the salivary glands. The purpose of this study was to explore the roles of sine oculis homeobox homolog 1 (SIX1), malic enzyme 2 (ME2), and AP-2 complex subunit mu (AP2M1) in AdCC and MEC, as well as the potential relationship between SIX1, ME2, AP2M1, and proliferation marker cyclin D1. MATERIAL AND METHODS: Immunohistochemistry was performed on human salivary gland tissue microarrays that contained 76 normal salivary glands (NSGs), 14 pleomorphic adenomas (PMAs), 81 AdCCs, and 52 MECs. RESULTS: We observed that the expression levels of SIX1 and ME2 were significantly elevated in AdCC and MEC when compared with NSG and PMA. In addition, we detected that AP2M1 was overexpressed in AdCC and MEC when compared with NSG. We also found that SIX1 and AP2M1 were positively associated with cyclin D1. CONCLUSIONS: These results may prove that SIX1 and AP2M1 are involved in the proliferation of AdCC and MEC to cause tumor growth.

Overexpression of Malic Enzyme 2 Indicates Pathological and Clinical Significance in Oral Squamous Cell Carcinoma.

Our study investigated the expression of malic enzyme 2 (ME2) in human oral squamous cell carcinoma (OSCC) and associated pathological and clinical pattern. We demonstrated that human OSCC tissues expressed a high level of ME2, and the overexpression of ME2 is closely connected to a high pathological grade, lymphatic metastasis, large tumor size and human papillomavirus (HPV) (P < 0.001). Similarly, high levels of ME2 expression in OSCC tissue were shown to be correlated with poor prognosis (P < 0.05). The expression of ME2 was correlated with Slug, SOX2, and aldehyde dehydrogenase-1 (ALDH1) immunoreactivity.ME2 was shown to be overexpressed in OSCC tissue and indicated a poor prognosis for OSCC. ME2 may be correlated with several immune markers.

Expression of inositol polyphosphate 4-phosphatase type II and the prognosis of oral squamous cell carcinoma.

Inositol polyphosphate 4-phosphatase type II (INPP4B) is a phosphoinositide phosphatase that plays complex roles in the pathogenesis of different tumors. We aimed to explore the expression, clinicopathological significance, and prognostic value of INPP4B in oral squamous cell carcinoma (OSCC). Tissue microarrays that included samples from 176 primary OSCCs, 42 normal mucosae, and 69 dysplastic tissues were used for immunostaining analyses of INPP4B protein. Aperio ScanScope CS scanner and aperio quantification software were used to scan the microarrays and score the staining, respectively. We also evaluated the correlation between INPP4B expression and clinical parameters, pathological grades, node-positive status, and immune-related markers. Expression of INPP4B was statistically significantly upregulated in human primary OSCC tissues compared with dysplastic and normal tissues. Additionally, we found that patients with strong expression of INPP4B had a statistically significantly poorer overall survival than patients with weak expression of INPP4B. Furthermore, our study indicated that expression of INPP4B in OSCC was positively associated with expression of p-S6Ser235/236 , p-CADSer1859 , and certain immune checkpoints (B7-H4, Galectin-9). Therefore, INPP4B may be an independent prognostic indicator for patients with OSCC, in which it might function as an oncoprotein.

Expression and Prognostic Value of IFIT1 and IFITM3 in Head and Neck Squamous Cell Carcinoma.

OBJECTIVES: Interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) and interferon-induced transmembrane protein 3 (IFITM3) are commonly induced by type I interferon. The study aims to investigate the expression and clinical significance of IFIT1 and IFITM3 in head and neck squamous cell carcinoma (HNSCC). METHODS: Immunohistochemistry was applied on tissue microarray to reveal IFIT1 and IFITM3 expression in 275 HNSCC, 69 dysplasia, and 42 normal mucosa samples. The clinicopathologic features associated with IFIT1 and IFITM3 expression in HNSCC patients were analyzed. RESULTS: IFIT1 and IFITM3 were highly expressed in HNSCC tissues. High expression of IFIT1 and IFITM3 predicts a negative prognosis for patients (P < .01). IFIT1 and IFITM3 expression was associated with programmed cell death ligand 1, B7-H4, V-domain Ig suppressor of T-cell activation, indoleamine 2,3-dioxygenase, and macrophage marker immunoreactivity. CONCLUSIONS: IFIT1 and IFITM3 were overexpressed in HNSCC and indicated poor prognoses for patients with HNSCC. IFIT1 and IFITM3 expression was correlated with several immune checkpoint molecules and tumor-associated macrophage markers.

Expression and clinicopathologic significance of coxsackie-adenovirus receptor in oral squamous cell carcinoma.

OBJECTIVE: This study aimed to explore the relationship between the expression of the coxsackie-adenovirus receptor (CAR) in oral squamous cell carcinoma (OSCC) and the clinicopathologic parameters associated with the disease. The diagnostic and prognostic potential of CAR in OSCC was also investigated. STUDY DESIGN: Immunohistochemistry was performed on human tissue microarrays, containing 42 oral mucosa, 69 dysplasia, and 176 OSCC tissue sections, to reveal the expression pattern of CAR. Statistical analysis was used to determine the correlation between CAR expression and the patient survival rate as a measure of the prognostic value of CAR. RESULTS: CAR was overexpressed in human OSCC tissues (P = .002), and higher expression of CAR was associated with a lower survival rate, which was not statistically significant (P = .123). In addition, patients with OSCC in the human papillomavirus (HPV)-positive group showed significantly higher CAR expression compared with the HPV- negative group (P = .0491). CONCLUSIONS: This study indicated that CAR expression was upregulated in human OSCC and that patients with OSCC with higher expression of CAR had a lower survival rate. Moreover, CAR expression may be associated with HPV infection.

Increased Expression of LAMTOR5 Predicts Poor Prognosis and Is Associated with Lymph Node Metastasis of Head and Neck Squamous Cell Carcinoma.

Late endosomal/lysosomal adaptor and MAPK and mTOR activator 5 (LAMTOR5) is a novel oncoprotein associated with several human malignancies, but its clinical role in head and neck squamous cell carcinoma (HNSCC) remains unclear. The present study aims to investigate the clinical and pathological significance of LAMTOR5 in HNSCC. We utilized immunohistochemical staining of human tissue microarrays (210 primary HNSCC, 42 normal oral mucosae, 69 oral epithelial dysplasia, and 68 metastasis lymph nodes) to explore the clinical and pathological significance of LAMTOR5 in HNSCC. Additionally, expression level of LAMTOR5 in immunoreactivity of Pten conditional knock out (Pten cKO) mice HNSCC was also assessed. We found LAMTOR5 was overexpressed in human and Pten cKO mice HNSCC, and its expression was significantly associated with patients' overall survival, lymph node metastasis and lymph node grade. Furthermore, LAMTOR5 expression was significantly correlated with the expression of p-AktSer473, p-S6Ser235/236, immune checkpoints (PD-L1, Galectin 9, VISTA and B7-H4) and macrophage markers (CD68 and CD163). In Pten cKO mice HNSCC, it was also significantly correlated with VISTA and F4/80. Consequently, we consider that high expression of LAMTOR5 might be a poor prognostic indicator and correlated with the immunosuppression of tumor microenvironment.

The Expression Patterns and Associated Clinical Parameters of Human Endogenous Retrovirus-H Long Terminal Repeat-Associating Protein 2 and Transmembrane and Immunoglobulin Domain Containing 2 in Oral Squamous Cell Carcinoma.

Human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2) and transmembrane and immunoglobulin domain containing 2 (TMIGD2) are new immune checkpoint molecules of the B7:CD28 family; however, little research has been performed on these immune checkpoint molecules. In this study, we used oral squamous cells carcinoma (OSCC) tissue microarrays and immunohistochemistry methods to investigate the expression patterns of HHLA2 and TMIGD2 in OSCC. After comparing the HHLA2 and TMIGD2 expression levels in OSCC, dysplasia, and mucosa, we found increased HHLA2 expression in OSCC and dysplasia, while the TMIGD2 expression was decreased in OSCC and dysplasia. Using the Kaplan-Meier method and log-rank test, we found that higher HHLA2 or TMIGD2 expression levels in OSCC indicate poor prognosis. Furthermore, two-tailed Pearson's statistical analysis revealed that the HHLA2 expression levels in OSCC, dysplasia, and mucosa were positively correlated with the T cell immunoglobulin and mucin-domain containing-3 (TIM3), lymphocyte-activation gene 3 (LAG3), B7 homolog 3 protein (B7-H3), B7 homolog 4 protein (B7H4), and V-domain Ig suppressor of T cell activation (VISTA) levels, while the TMIGD2 expression levels in OSCC, dysplasia, and mucosa were inversely correlated with the TIM3, LAG3, and B7H3 levels. Our current study demonstrates that HHLA2 may serve as an immune target for OSCC therapy and that the TMIGD2 expression level in OSCC could forecast patient prognosis.

Preoperative Anemia or Low Hemoglobin Predicts Poor Prognosis in Gastric Cancer Patients: A Meta-Analysis.

BACKGROUND: The prognostic value of preoperative anemia in gastric cancer remains unclear. Therefore, the purpose of the present study is to evaluate the prognostic value of preoperative anemia in gastric cancer. METHODS: We searched Embase and PubMed databases for relevant studies from inception to March 2018. The prognostic value of preoperative anemia in gastric cancer was determined by calculating the hazard ratio (HR) and the corresponding 95% confidence interval (CI) as effect measures. A random effect model was used in cases in which there was significant heterogeneity; otherwise, a fixed effect model was used. Statistical analyses were performed using Stata software. RESULTS: Seventeen studies involving 13,154 gastric cancer patients were included. The estimated rate of preoperative anemia was 36% (95%CI = 27-44%). The overall survival of preoperative anemia was poor (HR = 1.33, 95%CI = 1.21-1.45). Moreover, disease-free survival was significantly lower in patients with preoperative anemia compared with those without this condition (HR = 1.62, 95%CI = 1.13-2.32). These findings were corroborated by the results of subgroup analyses. CONCLUSIONS: The results indicate that preoperative anemia predicts poor prognosis in gastric cancer, including overall survival and disease-free survival. Therefore, preoperative anemia may be a convenient and cost-effective blood-derived prognostic marker for gastric cancer.

Overexpression of FAM3C is associated with poor prognosis in oral squamous cell carcinoma.

Expression of the family with sequence similarity 3 member C (FAM3C) is necessary for the epithelial-mesenchymal transition (EMT). However, the expression level and clinicopathological significance of FAM3C in oral squamous cell carcinoma (OSCC) has not been thoroughly elucidated to date. We performed immunohistochemical staining on human OSCC specimens with FAM3C, co-inhibitory immune checkpoints, EMT markers, and cancer stem cells (CSCs) markers to analyze the expression levels and clinicopathological features of FAM3C in OSCC. There were 210 primary OSCC specimens, 69 oral epithelial dysplasia and 42 normal oral mucosae in our human OSCC tissue microarrays cohort. We observed that FAM3C expression was upregulated in OSCC compared with normal mucosa and epithelial dysplasia (P < 0.001). Moreover, patients with higher FAM3C expression levels had a worse prognosis than those with lower expression levels (P < 0.05). Also, FAM3C expression was positively correlated with the immune checkpoints PD-L1, VISTA, and B7-H4, the EMT marker Slug and the CSC markers SOX2 and ALDH1. In conclusion, these findings suggested that overexpression of FAM3C in human OSCC may predict a poor prognosis for OSCC patients.

High expression of GPNMB predicts poor prognosis in head and neck squamous cell carcinoma.

Glycoprotein non-metastatic protein B (GPNMB) is a transmembrane glycoprotein that is highly expressed in several malignancies compared with its expression in matched healthy tissues. The aim of this study was to investigate the clinical characteristics and prognostic value of GPNMB expression in tumor tissue derived from a cohort of patients with head and neck squamous cell carcinoma (HNSCC). GPNMB expression in human HNSCC, oral dysplasia and normal mucosal tissue was evaluated by immunohistochemistry (IHC). The correlations of GPNMB expression with the clinical characteristics of HNSCC were assessed by one-way ANOVA and t test analyses. Survival data were analyzed using Kaplan-Meier analysis and the Cox proportional hazards model. GPNMB was highly expressed in HNSCC tissue compared with dysplasia and normal mucosal tissue. Additionally, a high level of GPNMB expression in HNSCC was associated with poor prognosis (P<0.01). In the analysis of tumor-node-metastasis (TNM) staging, a high GPNMB expression level in HNSCC tissue, as well as metastatic lymph node tissue, correlated with an advanced N stage. In conclusion, GPNMB was overexpressed in human HNSCC tissue and predicted poor prognosis in human HNSCC tissue. In addition, GPNMB expression was closely correlated with N stage in patients with HNSCC.