Transcriptome sequencing identifies ANLN as a promising prognostic biomarker in bladder urothelial carcinoma

Abstract

The prognosis of bladder urothelial carcinoma (BLCA) varies greatly even for patients with similar pathological characteristics. We conducted transcriptome sequencing on ten pairs of BLCA samples and adjacent normal tissues to identify differentially expressed genes. Anillin (ANLN) was identified as a transcript that was significantly up-regulated in BLCA samples compared with normal tissues. Prognostic power of candidate gene was studied using qRT-PCR and immunohistochemistry on 40 and 209 patients, respectively. Patients with elevated ANLN expression level was correlated with poorer cancer-specific (median, 22.4 vs. 37.3 months, p = 0.001), progression-free (median, 19.7 vs. 27.9 months, p = 0.001) and recurrence-free survival (median, 17.1 vs. 25.2 months, p = 0.011) compared with low ANLN expression. Public datasets TCGA and NCBI-GEO were analyzed for external validation. Knockdown of ANLN in J82 and 5637 cells using small interfering RNA significantly inhibited cell proliferation, migration, and invasion ability. Moreover, knockdown of ANLN resulted in G2/M phase arrest and decreased expression of cyclin B1 and D1. Microarray analysis suggested that ANLN played a major role in cell migration and was closely associated with several cancer-related signaling pathways. In conclusion, ANLN was identified as a promising prognostic biomarker which could be used to stratify different risks of BLCA.

ANLN and TLE2 in Muscle Invasive Bladder Cancer: A Functional and Clinical Evaluation Based on In Silico and In Vitro Data

“…Previous research has established that knockdown of ANLN could significantly inhibit the proliferation of bladder cancer both in vitro and in vivo. Furthermore, knockdown of ANLN strongly suppressed the migration and invasion ability of J82 and 5637 bladder cancer cell lines [16]. Additionally, in upper urinary tract urothelial carcinoma, overexpression of ANLN in the nucleus is a poor prognostic factor, which was confirmed by data on protein levels, while low expression of ANLN in the cytoplasm is a poor prognosis maker [23].…”

“…In The Cancer Genome Atlas (TCGA) cohort, higher ANLN expression was associated with worse OS (n = 246 with low expression, n = 161 with high expression; median survival, 18.07 vs. 15.31 months, and p = 0.0144) and disease-free survival (DFS) (n = 246 with low expression, n = 161 with high expression; median survival, 18.82 vs. 13.99 months, and p = 0.0045, Figure 2a,b). In contrast, higher TLE2 expression was associated with more favorable OS (n = 250 with low expression, n = 157 with high expression; median survival, 16.69 vs. 18.99 months, and p = 0.0054) and DFS (n = 250 with low expression, n = 157 with high expression; median survival, 15.31 vs. 16.79 months, and p = 0.0094, Figure 2c,d). In the TCGA cohort, correlation between ANLN and TLE2 expression and stage showed that ANLN was significantly expressed in pT3 and pT4 (higher stages, median expression 9.95 vs. 10.16, and p = 0.0109, Figure S1a), while TLE2 was dominantly expressed in pT2 (lower stage, median expression 9.88 vs. 9.73, and p = 0.0228, Figure S1b).…”

“…Previous studies found that ANLN expression levels were significantly up-regulated in a variety of tumor tissues, including breast, ovarian, colon, lung, and pancreatic cancers [10][11][12][13][14][15]. Furthermore, ANLN and its encoded protein are highly expressed in BLCA tissues, and their expression levels are positively correlated with the pathological grade and stage of BLCA [16]. However, the involved signaling pathways and the interacting molecular targets in the regulation of BLCA biological function are in discussion.…”

Overexpression of ANLN in lung adenocarcinoma is associated with metastasis

“…8 Previous studies have found that ANLN can regulate actin cytoskeletal dynamics in podocytes. 9 Previous studies have also confirmed that ANLN expression is associated with prognosis in patients with breast, 10 bladder, 11 and colorectal cancers. 12 Pandi et al 13 confirmed that ANLN is a Wnt/β-catenin responsive gene in gastric cancer and can regulate the proliferation of gastric cancer cells.…”

ANLN-induced EZH2 upregulation promotes pancreatic cancer progression by mediating miR-218-5p/LASP1 signaling axis

“…In normal tissues, ANLN expression is higher in the placenta, brain and testis, and lower in the lung, heart, liver and spleen [8]. Many recent studies suggests that ANLN is upregulated in numerous cancer types, including cervical cancer, prostate cancer, anaplastic thyroid carcinoma, breast cancer, lung carcinogenesis, bladder urothelial carcinoma, pancreatic cancer and nasopharyngeal carcinoma [9][10][11][12][13][14][15][16]. Functionally, increasing evidence has indicated that ANLN is critical for growth and metastasis of cancer cells.…”