Molecular characterization and integrative genomic analysis of a panel of newly established penile cancer cell lines

Zhou, Qiang; Deng, Congying; Li, Zai Shang; Chen, Jie Ping; Yao, Kai; Huang, Kang; Liu, Ting Yu; Liu, Zhuo Wei; Qin, Zi Ke; Zhou, Fangjian; Huang, Wenlin; Han, Hui; Liu, Ranyi

doi:10.1038/s41419-018-0736-1

Cited by 34 publications

(38 citation statements)

References 47 publications

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“…We also identified novel genes, such as CASP8 (caspase 8; frequency: 4/30), FLG (filaggrin; frequency: 3/30), SLITRK2 (SLIT and NTRK‐like family member 2; frequency: 3/30), CCDC168 (coiled‐coil domain containing 168; frequency: 3/30), TRRAP (transformation/transcription domain‐associated protein; frequency: 3/30) and TTN (titin; frequency: 3/30). Among the 11 frequently mutated genes identified in our study, alterations in TP53 , HRAS , NOTCH1 , PIK3CA and TTN were also frequently observed in the cell lines derived from Chinese penile cancer patients . On the other side, of the critical genes with functional mutations identified by Zhou et al .…”

Section: Discussionsupporting

confidence: 71%

“…On the other side, of the critical genes with functional mutations identified by Zhou et al . in the panel of PSCC cell lines, 10 were found to be altered in our sample too. Additionally, we also observed many less frequent alterations, which often were confounded by random passenger events.…”

Section: Discussionsupporting

confidence: 71%

“…Zhou et al . have recently established a panel of PSCC cell lines derived from Chinese penile cancer patients and identified dozens of critical genes with functional mutations . Functional alterations in 10 of these genes were also observed in our sample, and they are HRAS , NOTCH1 , TP53 , TTN , CIITA , FBXW7 , MAP2K3 , AFF3 , NIN and TET2 .…”

Section: Resultsmentioning

confidence: 99%

“…Immunohistochemical analysis and Western blotting were performed according to the standard protocol with the following antibodies: CASP8 (Novus, St. Louis, MO; NB100‐56527), TRRAP (Biorbyt, San Francisco, CA; orb158656), TTN (Sigma, St. Louis, MO; SAB1400284), FLG (Abcam, Cambridge, UK; ab81468), CCDC168 (Abcam, ab151018), FBXW7 (Abcam, ab109617), H‐RAS (Santa Cruz, Santa Cruz, CA; sc‐29), PIK3CA (Abcam, ab87530), Notch1 (Cell Signaling Technology [CST], Danvers, MA; 3608), PARP (CST, 9542) and GAPDH (Sigma, G9545). The penile cancer cell line Penl1 was used for gene function analysis and cultured in DMEM medium with 10% fetal bovine serum. Small interfering RNA (siRNA) transfection was performed with Lipofectamine 3,000 (Invitrogen, Carlsbad, CA) according to the manufacturer's instructions.…”

Section: Methodsmentioning

confidence: 99%

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Mutational landscape of penile squamous cell carcinoma in a Chinese population

Wang

Chen

et al. 2019

Intl Journal of Cancer

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Penile squamous cell carcinoma (PSCC) is a malignancy that affects the skin and tissues of the penis, but the knowledge of pathogenesis and carcinogenesis is limited. Here, we characterize the PSCC genomic landscape using whole‐exome sequencing. Of the 30 paired blood and tumor samples, we identified recurrent mutations in 11 genes; confirmed previous findings for FAT1 (4/30), HRAS (4/30), NOTCH1 (4/30), TP53 (3/30) and PIK3CA (3/30); and revealed novel candidate driver genes [CASP8 (4/30), SLITRK2 (3/30), FLG (3/30) and TRRAP (3/30)]. Our in vitro experiments suggested CASP8 was involved in mediating TRAIL‐induced apoptosis of penile cancer cell lines. We also observed the frequently altered pathways for potential therapeutic implications: alterations in the Notch (30% of sample altered), RTK–RAS (26.7% altered) and Hippo (23.3% altered) pathways accounted for over 50% of tumors. The frequently altered genes (>10%) in these pathways were proved to be expressed in penile tumors by immunohistochemistry assay. These findings provide new insight into the mutational and pathway landscapes of PSCC and suggest potential novel therapeutic opportunities for this malignancy.

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Section: Discussionsupporting

confidence: 71%

Section: Discussionsupporting

confidence: 71%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Mutational landscape of penile squamous cell carcinoma in a Chinese population

Wang

Chen

et al. 2019

Intl Journal of Cancer

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“…PSCC cell lines (Penl1, Penl2, and 149RCa) were established in our laboratory. [28][29][30] HaCaT and 293T cells were obtained from the CAS Type Culture Collection of the Chinese Academy of Sciences (Shanghai, China). All cell lines were maintained in Dulbecco's modified Eagle medium supplemented with 10% fetal bovine serum (Thermo Fisher Scientific, Waltham, MA, USA).…”

Section: Cell Lines and Establishment Of Stable Cell Linesmentioning

confidence: 99%

Elevated serum LAMC2 is associated with lymph node metastasis and predicts poor prognosis in penile squamous cell carcinoma

Zhou

Deng

Chen

et al. 2018

CMAR

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PurposeMolecular biomarkers, especially serologic factors, have been widely applied in cancer diagnosis and patient follow-up. However, there are few valuable prognostic factors in penile squamous cell carcinoma (PSCC). Here, the authors investigated whether laminin gamma 2 (LAMC2) expression, especially serum LAMC2 (sLAMC2) level, was a suitable prognostic factor that could aid in the prediction of survival in PSCC.Patients and methodsThis study included 114 PSCC patients. Reverse transcription-quantitative polymerase chain reaction, Western blotting, and immunohistochemistry were performed to detect LAMC2 expression; enzyme-linked immunosorbent assays were used to test sLAMC2 concentration; and a Transwell assay and an in vivo experiment in nude mice were used to test PSCC cell migration, invasion, and metastasis. The chi-squared test was used to analyze the association between LAMC2 level and clinical parameters, the Cox proportional hazards regression model was used to evaluate the hazard ratio for death, and Kaplan–Meier analysis with a log-rank test was used for the survival analysis.ResultsLAMC2 was overexpressed in PSCC tissues, and the LAMC2 expression level was higher in metastatic lymph node (LN) tissues than in primary cancer tissues; moreover, the LAMC2 levels in primary cancer tissues and sLAMC2 were higher in patients with LN metastasis than in those without LN metastasis. Upregulated LAMC2 facilitated the migration, invasion, and epithelial-to-mesenchymal transition of PSCC cells in vitro and promoted LN metastasis of PSCC cells in nude mice. Elevated LAMC2 levels were strongly correlated with advanced clinicopathologic parameters, especially LN metastasis, in PSCC patients and predicted shorter disease-specific survival. The predictive value of sLAMC2 is superior to that of C-reactive protein and squamous cell carcinoma antigen previously reported in PSCC patients, and a stratification analysis revealed that the level of sLAMC2 had a higher predictive value for disease-specific survival in early penile cancer (especially at the N0/X stage) than in later-stage penile cancer.ConclusionThese findings suggest that sLAMC2 is a potential serologic prognostic marker in PSCC and could aid in risk stratification in early-stage PSCC patients.

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Up‐regulation of indoleamine 2,3‐dioxygenase 1 (IDO1) expression and catalytic activity is associated with immunosuppression and poor prognosis in penile squamous cell carcinoma patients

Zhou

Han

et al. 2020

Cancer Communications

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Background Indoleamine 2,3‐dioxygenase 1 (IDO1) and tryptophan (Trp) catabolism have been demonstrated to play an important role in tumor immunosuppression. This study examined the expression and catalytic activity of IDO1 in penile squamous cell carcinoma (PSCC) and explored their clinical significance. Methods IDO1 expression level, serum concentrations of Trp and kynurenine (Kyn) were examined in 114 PSCC patients by immunohistonchemistry and solid‐phase extraction‐liquid chromatography‐tandem mass spectrometry. The survival was analyzed using Kaplan‐Meier method and the log‐rank test. Hazard ratio of death was analyzed via univariate and multivariate Cox regression. Immune cell types were defined by principal component analysis. The correlativity was assessed by Pearson's correlation analysis. Results The expression level of IDO1 in PSCC cells was positively correlated with serum Kyn concentration and Kyn/Trp radio (KTR; both P < 0.001) but negatively correlated with serum Trp concentration (P = 0.001). Additionally, IDO1 up‐regulation in cancer cells and the increase of serum KTR were significantly associated with advanced N stage (both P < 0.001) and high pathologic grade (P = 0.008 and 0.032, respectively). High expression level of IDO1 in cancer cells and serum KTR were associated with short disease‐specific survival (both P < 0.001). However, besides N stage (hazard radio [HR], 6.926; 95% confidence interval [CI], 2.458‐19.068; P < 0.001) and pathologic grade (HR, 2.194; 95% CI, 1.021‐4.529; P = 0.038), only serum KTR (HR, 2.780; 95% CI, 1.066‐7.215; P = 0.036) was an independent predictor for PSCC prognosis. IDO1 expression was positively correlated with the expression of interferon‐γ (IFNγ, P < 0.001) and immunosuppressive markers (programmed cell death protein 1, cytotoxic T‐lymphocyte‐associated protein 4 and programmed death‐ligand 1 and 2; all P < 0.05), and the infiltration of immune cells (including cytotoxic T lymphocytes, regulatory T lymphocytes, tumor‐associated macrophages, and myeloid‐derived suppressor cells; all P < 0.001) in PSCC tissues. Furthermore, the expression of IDO1 was induced by IFNγ in a dose‐dependent manner in PSCC cells. Conclusions IFNγ‐induced IDO1 plays a crucial role in immunoediting and immunosuppression in PSCC. Additionally, serum KTR, an indicator of IDO1 catabolic activity, can be utilized as an independent prognostic factor for PSCC.

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Molecular characterization and integrative genomic analysis of a panel of newly established penile cancer cell lines

Cited by 34 publications

References 47 publications

Mutational landscape of penile squamous cell carcinoma in a Chinese population

Mutational landscape of penile squamous cell carcinoma in a Chinese population

Elevated serum LAMC2 is associated with lymph node metastasis and predicts poor prognosis in penile squamous cell carcinoma

Up‐regulation of indoleamine 2,3‐dioxygenase 1 (IDO1) expression and catalytic activity is associated with immunosuppression and poor prognosis in penile squamous cell carcinoma patients

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