Construction and validation of a prognostic model for tongue cancer based on three genes signature.

Tongue squamous cell carcinoma (TSCC) has a poor prognosis and destructive characteristics. Reliable biomarkers are urgently required to predict disease outcomes and to guide TSCC treatment. This study aimed to develop a multigene signature and prognostic nomogram that can accurately predict the prognosis of patients with TSCC. We screened differentially expressed genes associated with TSCC using The Cancer Genome Atlas dataset. Based on this, we developed a new multi-mRNA gene signature using univariate Cox regression, Least Absolute Shrinkage and Selection Operator regression, and multivariate Cox regression. We used the concordance index to evaluate the accuracy of this new multigene model. Moreover, we performed receiver operating characteristic and Kaplan-Meier survival analyses to assess the predictive ability of the new multigene model. In addition, we created a prognostic nomogram incorporating clinical and pathological characteristics, with the aim of enhancing the adaptability of this model in practical clinical settings. We successfully developed a new prognostic model based on the expression levels of these 3 mRNAs that can be used to predict the prognosis of patients with TSCC. This prediction model includes 3 genes: KRT33B, CDKN2A, and CA9. In the validation set, the concordance index of this model was 0.851, and the area under the curve was 0.778 and 0.821 in the training and validation sets, respectively. Kaplan-Meier survival analysis showed that regardless of whether it was in the training or validation set, the prognosis of high-risk patients was significantly worse than that of low-risk patients (P < .001). Multivariate Cox regression analysis revealed that this model was an independent prognostic factor for patients with TSCC (P < .001). Our study suggests that this 3-gene signature model has a high level of accuracy and predictive ability, is closely related to the overall survival rate of patients with TSCC, and can independently predict the prognosis of TSCC patients with high accuracy and predictive ability.

Involvement of KLRK1 in immune infiltration of head and neck squamous cell carcinoma correlates with favorable prognosis.

Head and neck squamous cell carcinoma (HNSCC) is a malignancy commonly found in the head and neck region, with a low 5-year survival rate. Although immunotherapy has made significant progress, its efficacy in HNSCC treatment remains unsatisfactory. Killer cell lectin-like receptor K1 (KLRK1), a marker highly expressed in immune cells, can bind to its ligands expressed by cancer cells to exert its antitumor effect. However, the role of KLRK1 in HNSCC has yet to be studied extensively. This study aimed to explore the involvement of KLRK1 in immune infiltration of HNSCC and its correlation with prognosis. We analyzed KLRK1 expression data from the Cancer Genome Atlas database. The relationship between KLRK1 and immune cell infiltration has also been investigated. Finally, we analyzed the association between the expression of KLRK1 and its ligands and the prognosis of patients with HNSCC. We found that KLRK1 was highly expressed in HNSCC and correlated with better prognosis. KLRK1 expression was correlated with age, histological grade, HPV infection, pT, pN, pTNM stage, primary site, and survival status. High expression levels of KLRK1 have been linked to high levels of immune cell infiltration, particularly CD4/8 (+) T lymphocytes. Among the ligands of KLRK1, UL16 binding protein (ULBP) 1-3 showed high expression, which was associated with an increased risk of death. Notably, the expression of KLRK1 was negatively correlated with ULBP1-3. Patients with high levels of ULBP2/3 expression in tonsil carcinoma had poorer prognosis than those with low levels (P < .01), whereas ULBP1 expression levels had no significant effect on tonsil carcinoma prognosis (P = .770). The expression levels of ULBP1/3 were correlated with worse prognosis in patients with laryngeal cancer (P < .05), whereas there was no significant correlation between ULBP2 expression levels and overall survival (P = .269). Our study revealed that KLRK1 is highly expressed in HNSCC and is associated with a better prognosis and immune infiltration. Patients with high expression of KLRK1 ligands exhibited worse prognoses, possibly because of the expression of more soluble ligands.

Influence of advanced age on the prognosis of triple-negative breast cancer patients: A surveillance, epidemiology, and end results-based study.

Introduction: Age at diagnosis has shown significant effect on the prognosis in breast cancer patients. However, whether age is an independent risk factor remains controversial. Furthermore, population-based estimates of age on the prognosis impact in triple-negative breast cancer are still lacking. The aim of this study was to analyze the influence of age and other factors on the prognosis and survival of triple-negative breast cancer patients. Materials and Methods: We used the surveillance, epidemiology, and end results program data from 2011 to 2014. A retrospective cohort study was conducted to investigate prognosis factors in triple-negative breast cancer. Patients were divided into two groups according to age at diagnosis: 75 + years (the elderly patients) and < 75 years (reference group). The clinicopathologic characteristics of different age groups were compared using Chi-square tests. Overall survival (OS) and breast cancer-specific survival were analyzed using the Kaplan-Meier method. Prognostic factors were compared using the Cox proportional hazards model. We also analyzed the difference of distant metastasis at initial diagnosis on every group. Results: A total of 21,429 triple-negative breast cancer patients were included in our study. The mean breast cancer-specific survival time of triple-negative breast cancer was 70.5 months for the reference group and 62.4 months for the elderly group. Survival analysis showed that the breast cancer-specific survival rate was 78.9% for the reference group and 67.4% for the elderly group. The mean OS time was 69.0 months for the reference group and 52.3 months for the elderly group. The 5-year OS of triple-negative breast cancer patients was 76.4% for the reference group and 51.3% for the elderly group. The prognosis of elderly patients is much poor than reference group. Univariate Cox regression analysis showed that age, race, marital status, histological grade, stage, T, N, M, surgery, radiotherapy, and chemotherapy were risk factors for triple-negative breast cancer (TNBC) (P < 0.05). Multivariate Cox regression analysis showed that age, race, marital status, histological grade, stage, T, N, M, surgery, radiotherapy, and chemotherapy were independent risk factors for TNBC (P < 0.05). Conclusions: Age is an independent risk factor for the prognosis of TNBC patients. Elderly triple-negative breast cancer patients displayed obvious lower 5-year survival rate compared to reference group, even though they have better grade stage, minor tumor, less lymph node metastasis. The lower rate of marital status, radiotherapy, chemotherapy, surgery, and higher rate of metastasis at diagnosis must contribute to their poor outcome.

T1-2N1M0 triple-negative breast cancer patients from the SEER database showed potential benefit from post-mastectomy radiotherapy.

The effects of post-mastectomy radiotherapy (PMRT) on different subtypes of T1-2N1M0 breast cancer remain controversial. Patients with T1-2N1M0 breast cancer treated by mastectomy or mastectomy and PMRT were identified from the 2010-2013 dataset from the Surveillance, Epidemiology and End Results (SEER) registry. A total of 7,466 patients with the 7th American Joint Committee on Cancer stage (Tumor-Node-Metastasis stages 1-2, 1 and 0, respectively) including 2,760 cases (36.97%) treated by mastectomy and PMRT and 4,706 cases (63.03%) treated by mastectomy alone were analyzed in this study. The follow-up time for patients in the dataset used from the SEER registry was 0-59 months. The breast cancer-specific survival (BCSS) of the patients was derived from the SEER dataset and stratified by treatment approach. A propensity score matching (PSM) analysis (experimental group: Control group ratio, 1:1) was conducted. Using univariate and multivariate analyses Cox proportional hazards analyses, PMRT was identified as an independent prognostic factor for triple-negative breast cancer (TNBC). Before PSM analysis, the BCSS favored PMRT in the hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)+ (P=0.025) and HR-/HER2- groups (P=0.010) but not in the HR+/HER2- (P=0.346) and HR-/HER2+ (P=0.288) groups. Following PSM analysis, BCSS favored PMRT alone in the TNBC (HR-/HER2-) group (P=0.025). Patients with T1-2N1M0 TNBC may benefit from radiotherapy post-mastectomy.

PGK1 is a Potential Survival Biomarker and Invasion Promoter by Regulating the HIF-1α-Mediated Epithelial-Mesenchymal Transition Process in Breast Cancer.

BACKGROUND/AIMS: Glycolysis, a multi-step enzymatic reaction, is considered to be the root of cancer development and progression. The aim of this study is to figure out which glycolysis enzyme participates in the progression of breast cancer and its possible mechanisms. MATERIALS: We firstly screened out PGK1 by performing an RT-PCR array of glycolysis-related genes in three paired breast cancer samples, and further investigated PGK1 using TCGA and our own database. The effect and mechanism of PGK1 on cell invasion was further explored both in vitro and using patient samples. RESULTS: PGK1 was most upregulated in T3N0 with distant metastases compared to those with no metastases. In the TCGA database, high PGK1 expression predicted poor overall survival (OS) in breast cancer and some other cancers (P< 0.001). In the validation cohort, high PGK1 expression was significantly correlated with larger tumor size (P=0.011) and advanced TNM stage (P=0.033), and PGK1 expression was an independent prognostic factor for OS and disease free survival (DFS) in both univariate and multivariate regression analyses (P< 0.05). Functional studies indicated that knockdown of PGK1 expression significantly inhibited invasion and reversed the epithelial-mesenchymal transition process in breast cancer cells (P< 0.05). Mechanistically, PGK1 increased HRE luciferase activity in a dose-dependent manner, while silencing PGK1 expression decreased HRE activity. CONCLUSION: High PGK1 expression was associated with poor prognosis in breast cancer, because PGK1 and HIF-1α formed a positive feed-forward loop and thus stimulated breast cancer progression and metastases. Based on these results, PGK1 may serve as a promising biomarker and target therapy for breast cancer.

Laminin is over expressed in breast cancer and facilitate cancer cell metastasis.

AIM OF STUDY: Breast cancer invasion and metastasis is the main reason for the failure, and laminin is involved in it. This study intends to explore the expression of laminin in breast cancer and normal breast tissue and its clinical significance. MATERIALS AND METHODS: We use immunohistochemical assay for the detection of breast infiltrating ductal cancer tissues and normal breast tissues of laminin expression and discuss their role in breast cancer invasion and metastasis. RESULTS: Our results showed that laminin was positive expressed in normal breast tissue, and strongly positive expressed but lost its' continuity in the breast cancer tissue. CONCLUSION: This results revealed laminin is involved in breast cancer invasion and metastasis, and we can use this to determine whether the integrity of a basement membrane for differential diagnosis of benign and malignant breast tumors.

HMGB2 is associated with malignancy and regulates Warburg effect by targeting LDHB and FBP1 in breast cancer.

BACKGROUND: High-mobility group box 2 (HMGB2) is implicated in tumorigenesis in various cancers. However, the clinical significance of HMGB2 signaling in human breast cancer progression remains unknown. METHODS: We investigated HMGB2 expression in 185 cases of primary breast cancer and matched normal breast tissue specimens, and explored the underlying mechanisms of altered HMGB2 expression as well as the impact of this altered expression on breast cancer growth and on aerobic glycolysis using in vitro and animal models of breast cancer. RESULTS: HMGB2 was more highly expressed in tumor-cell nuclei of breast cancer cells than in the adjacent normal breast tissues (P < 0.05). Higher HMGB2 expression correlated with larger tumor size (P = 0.003) and advanced tumor stage (P = 0.033). A Cox proportional hazards model revealed that HMGB2 expression was an independent prognostic factor for breast cancer after radical resection (P < 0.05). Experimentally, knockdown of HMGB2 expression by stable transfected shRNA significantly decreased the growth and glycolysis of breast cancer cells both in vitro and in mouse models. Mechanically, promotion of breast cancer progression by HMGB2 directly and significantly correlated with activation of LDHB expression and inactivation of FBP1 expression. CONCLUSIONS: These results disclose a novel role for HMGB2 in reprogramming the metabolic process in breast cancer cells by targeting LDHB and FBP1 and provide potential prognostic predictors for breast cancer patients.

Loss of fibulin-2 expression is involved in the inhibition of breast cancer invasion and forms a new barrier in addition to the basement membrane.

Previous studies have demonstrated that fibulin-2 may facilitate cancer cell invasion and metastasis during tumor progression. In the present study, immunohistochemical analyses of fibulin-2 and collagen IV expression in 35 patients with breast cancer were performed to define their localization and association with breast cancer tissue. Fibulin-2 was revealed to be expressed in all tissues surrounding the breast ducts and blood vessels in normal breast tissue, while its expression was not integrated in invasive ductal carcinoma or terminal duct-lobular unit. In malignant breast tissue, collagen IV was integrated around the duct, while fibulin-2 was expressed around collagen IV and was incomplete. These results demonstrated that fibulin-2 was associated with breast cancer invasion. Fibulin-2 expression decreased prior to basement membrane (BM) degradation, indicating that fibulin-2 forms an additional barrier around the BM. Therefore, it was proposed that fibulin-2 composes the general BM, which differs from the traditional BM. These results provide insight into extracellular matrix components and the involvement of fibulin-2 in tumor invasion and metastasis. Fibulin-2 was involved in the process of breast cancer development. It performed an important role in prevention of cancer cell penetration and metastasis.

Decreased expression of SOX17 is associated with tumor progression and poor prognosis in breast cancer.

The SOX17 (SRY-related HMG-box) transcription factor is involved in a variety of biological processes and is related to the tumorigenesis and progression of multiple tumors. However, the clinical application of SOX17 for breast cancer prognosis is currently limited. The aim of this study was to investigate the clinicopathologic and prognostic significance of SOX17 expression in human breast cancer. qPCR and western blot assays were performed to measure the expression of SOX17 in breast cancer cell lines and 30 matched pairs of breast cancer and corresponding noncancerous tissues. A SOX17 overexpression cell model was used to examine changes in cell growth in vitro. Immunohistochemical analyses were performed to retrospectively examine the prognostic impact of SOX17 expression in 187 additional breast cancer patients. Our results showed that SOX17 expression was decreased at both the messenger RNA (mRNA) and protein levels in the breast cancer cell lines and tissues, and that SOX17 overexpression could strongly suppress cell growth in vitro. Furthermore, the lack of SOX17 protein expression was strongly correlated with higher tumor grade (P = 0.002), lymph node metastasis (P < 0.001), and tumor node metastasis (TNM) stage (P = 0.001) and had poorer disease-free survival (DFS) and overall survival (OS) compared to normal SOX17 expression (P = 0.002 and 0.001, respectively). Univariate and multivariate analyses indicated that lower SOX17 expression was an independent prognostic factor for DFS (P = 0.007; HR = 2.854; 95 % CI 1.326-6.147) and OS (P = 0.005; HR = 5.035; 95 % CI 1.648-15.385) for breast cancer. Our findings indicate that SOX17 expression is a useful prognostic biomarker for breast cancer.

Sox17 promoter methylation in plasma DNA is associated with poor survival and can be used as a prognostic factor in breast cancer.

Aberrant DNA methylation that leads to the inactivation of tumor suppressor genes is known to play an important role in the development and progression of breast cancer. Methylation status of cancer-related genes is considered to be a promising biomarker for the early diagnosis and prognosis of tumors. This study investigated the methylation status of the Sox17 gene in breast cancer tissue and its corresponding plasma DNA to evaluate the association of methylation levels with clinicopathological parameters and prognosis.The methylation status of the Sox17 gene promoter was evaluated with methylation-specific polymerase chain reaction (MSP) in 155 paired breast cancer tissue and plasma samples and in 60 paired normal breast tissue and plasma samples. Association of Sox17 methylation status with clinicopathological parameters was analyzed by χ tests. Overall and disease-free survival (DFS) curves were calculated using Kaplan-Meier analysis, and the differences between curves were analyzed by log-rank tests.The frequency of Sox17 gene methylation was 72.9% (113/155) in breast cancer tissues and 58.1% (90/155) in plasma DNA. Sox17 gene methylation was not found in normal breast tissues or in their paired plasma DNA. There was a significant correlation of Sox17 methylation between corresponding tumor tissues and paired plasma DNA (r = 0.688, P < 0.001). Aberrant Sox17 methylation in cancer tissues and in plasma DNA was significantly associated with the tumor node metastasis stage (P = 0.035 and P = 0.001, respectively) and with lymph node metastasis (P < 0.001 and P = 0.001, respectively). Kaplan-Meier survival curves showed that aberrant Sox17 promoter methylation in cancer tissues and plasma DNA was associated with poor DFS (P < 0.005) and overall survival (OS) (P < 0.005). Multivariate analysis showed that Sox17 methylation in plasma DNA was an independent prognostic factor in breast cancer for both DFS (P = 0.020; hazard ratio [HR] = 2.142; 95% confidence interval [CI]: 1.128-4.067) and for OS (P = 0.001; HR = 4.737; 95% CI: 2.088-10.747).Sox17 gene promoter methylation may play an important role in breast cancer progression and could be used as a prognostic biomarker to identify patients at risk of developing metastasis or recurrence after mastectomy.

Relationship of CD44+CD24-/low breast cancer stem cells and axillary lymph node metastasis.

BACKGROUND: Axillary node staging plays an important role in the prognostic evaluation and planning of adjuvant treatment. Breast cancer stem cells, identified on the basis of CD44+CD24-/low expression, are associated with metastases and drug resistance. It is therefore important to investigate the proportion of CD44+CD24-/low breast cancer stem cells for the diagnosis of metastases in axillary nodes. METHODS: Thirty-two ipsilateral axillary lymph nodes were collected from patients diagnosed with invasive breast cancer. Each lymph node (LN) was divided into two equals - one was examined by H&E staining, while the other was made into a single cell suspension to study the content of CD44+CD24-/low cells by flow cytometry (FCM). The relationship was investigated between the content of CD44+CD24-/low cells and metastases in axillary nodes which were confirmed by histology. Associations were tested using the chi-square test (linear-by-linear association), and the significance level was set at a value of p < 0.05. RESULTS: In the 32 axillary nodes, the level of CD44+CD24-/low cells was determined to be between 0 and 18.4%: there was no presence of CD44+CD24-/low cells in 9 LNs, of which 2 had confirmed metastasis; there were less than 10% CD44+CD24-/low cells in 12 LNs, of which 6 had confirmed metastasis; and there were more than 10% CD44+CD24-/low cells in 11 LNs, of which 9 had confirmed metastasis. A higher percentage of detected CD44+CD24-/low cells was significantly associated with more confirmed LN metastases (p = 0.009). CONCLUSIONS: CD44+CD24-/low breast cancer stem cells might help clinicians to determine the presence of LN metastases. However, its prognostic value remains unclear, while histological diagnosis is still the gold standard.