Extracellular matrix (ECM), as an important framework for tumor microenvironment, plays important roles in many critical processes, including tumor growth, invasion, immune suppression, and drug resistance. However, few biomarkers of ECM-related genes (ERGs) have been developed for prognosis prediction and clinical treatment of bladder cancer (BC) patients. Bioinformatics analysis and LC-MS/MS analysis were used to screen differentially expressed ERGs in BC. Multivariate Cox regression analysis and Lasso regression analysis were used to construct and validate an ERGs-based prognostic prediction model for BC. Immunohistochemistry was used to detect the protein expression of hub gene-COL6A1 in BC patients. Using bioinformatics analysis from The Cancer Genome Atlas (TCGA) database and proteomic analysis from our BC cohort, we constructed and validated an effective prognostic prediction model for BC patients based on four differentially expressed ERGs (MAP1B, FBN1, COL6A1, and MFAP5). Moreover, we identified human collagen VI-COL6A1 was a hub gene in this prognostic prediction model and found that COL6A1 was closely related to malignancy progression, prognosis, and response to PD-1 inhibitor immunotherapy in BC. Our findings highlight the satisfactory predictive value of ECM-related prognostic models in BC and suggested that COL6A1 may be a potential biomarker in predicting malignant progression, prognosis, and efficacy of immunotherapy in BC.

Background Adrenocortical carcinoma (ACC) is a rare endocrine neoplasm, which is characterized by poor prognosis and high recurrence rate. Novel and reliable prognostic and metastatic biomarkers are lacking for ACC patients. This study aims at screening potential prognostic biomarkers and therapeutic targets of ACC through bioinformatic methods and immunohistochemical (IHC) analysis. Methods In the present study, by using the Gene Expression Omnibus (GEO) database we identified differentially expressed genes (DEGs) in ACC and validated these DEGs in The Cancer Genome Atlas (TCGA) ACC cohort. A DEGs-based signature was additionally constructed and we assessed its prognosis and prescient worth for ACC by survival analysis and nomogram. Immunohistochemistry (IHC) was used to verify the relationship between hub gene–GMNN expressions and clinicopathologic outcomes in ACC patients. Results A total of 24 DEGs correlated with the prognosis of ACC were screened from the TCGA and GEO databases. Five DEGs were subsequently selected in a signature which was closely related to the survival rates of ACC patients and GMNN was identified as the core gene in this signature. Univariate and multivariate Cox regression showed that the GMNN was an independent prognostic factor for ACC patients (P < 0.05). Meanwhile, GMNN was closely related to the OS and PFI of ACC patients treated with mitotane (P < 0.001). IHC confirmed that GMNN protein was overexpressed in ACC tissues compared with normal adrenal tissues and significantly correlated with stage (P = 0.011), metastasis (P = 0.028) and Ki-67 index (P = 0.014). Conclusions GMNN is a novel tumor marker for predicting the malignant progression, metastasis and prognosis of ACC, and may be a potential therapeutic target for ACC.

No abstract

Background:Adrenocortical carcinoma (ACC) is a rare endocrine neoplasm, which is characterized by poor prognosis and high recurrence rate. Novel and reliable prognostic and metastatic biomarkers are lacking for ACC patients. This study aims at screening potential prognostic biomarkers and therapeutic targets of ACC through bioinformatic methods and immunohistochemical (IHC) analysis. Methods: In the present study, by using the Gene Expression Omnibus (GEO) database we identified differentially expressed genes (DEGs) in ACC and validated these DEGs in The Cancer Genome Atlas (TCGA) ACC cohort. A DEGs-based signature was additionally constructed and we assessed its prognostic and prescient worth for ACC by survival analysis and nomogram. Immunohistochemistry (IHC) was used to verify the relationship between hub gene-GMNN expressions and clinicopathologic outcomes in ACC patients. Results: A total of 24 DEGs correlated with the prognosis of ACC were screened from the TCGA and GEO databases. Five DEGs were subsequently selected in a signature which was closely related to the survival rates of ACC patients. Among these genes, GMNN was identified as a hub gene and was independently associated with the survival of ACC. Meanwhile, in our cohort we also found that GMNN was significantly overexpressed in tumor tissues and was closely related to the pathological features and prognostic of ACC. Conclusions: GMNN is a novel tumor marker for predicting the malignant progression, metastasis and prognosis of ACC, and may be a potential therapeutic target for ACC.

Background Adrenocortical carcinoma (ACC) is a rare endocrine neoplasm, which is characterized by poor prognosis and high recurrence rate. Novel and reliable prognostic and metastatic biomarkers are lacking for ACC patients. This study aims at screening potential prognostic biomarkers and therapeutic targets of ACC through bioinformatic methods and immunohistochemical (IHC) analysis. Methods In the present study, by using the Gene Expression Omnibus (GEO) database we identified differentially expressed genes (DEGs) in ACC and validated these DEGs in The Cancer Genome Atlas (TCGA) ACC cohort. A DEGs-based signature was additionally constructed and we assessed its prognostic and prescient worth for ACC by survival analysis and nomogram. Immunohistochemistry (IHC) was used to verify the relationship between hub gene-GMNN expressions and clinicopathologic outcomes in ACC patients. Results A total of 24 DEGs correlated with the prognosis of ACC were screened from the TCGA and GEO databases. Five DEGs were subsequently selected in a signature which was closely related to the survival rates of ACC patients. Among these genes, GMNN was identified as a hub gene and was independently associated with the survival of ACC. Meanwhile, in our cohort we also found that GMNN was significantly overexpressed in tumor tissues and was closely related to the pathological features and prognostic of ACC. Conclusions GMNN is a novel tumor marker for predicting the malignant progression, metastasis and prognosis of ACC, and may be a potential therapeutic target for ACC.