Molecular genetic and clinical characteristic analysis of primary signet ring cell carcinoma of urinary bladder identified by a novel <scp>OR2L5</scp> mutation

Alradhi, Mohammed; Wen, Shuang; Safi, Mohammed; Al-Danakh, Abdullah; Wang, Honglong; Shopit, Abdullah; Sun, Min; Fan, Bo; Li, Xiancheng

doi:10.1002/cam4.5121

Cited by 4 publications

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“…All of this measure a significant gain in survival for a subset of people. Moreover, the anti-PD-1 monoclonal antibody nivolumab displayed a greater objective response rate and longer overall survival in patients with recurrent RCC compared to everolimus ( Motzer et al, 2015 ; Alradhi et al, 2022 ). Our study was prompted by information on good results from clinical trials, including targeted therapies.…”

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confidence: 99%

A novel nomogram and prognostic factor for metastatic renal cell carcinoma survival in the era of immune checkpoint inhibitors (ICIs)

et al. 2023

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Patients with metastatic renal cell cancer (mRCC) for whom surgery is ineffective may experience a poor prognosis. The different sites where cancer has spread, and the different ways to treat it in the immune checkpoint inhibitors era could help clinical decision-making. In this study, individuals with mRCC were selected from the SEER database between 2015 and 2016 based on the Food and Drug Administration (FDA) approval of ICIs. A total of 4011 mRCC patients were studied (2239 with lung metastasis vs. 797 with liver metastasis in the immune checkpoint inhibitors period). The age ≤ 64 years and male were the majority in all cases of mRCC. When the two groups (lung metastasis and liver metastasis) were compared, the liver metastasis group had more bone metastasis than the lung metastasis group (41.8% vs. 34.1%, p < 0.001), but the lung metastasis group had more brain metastasis (8.9% vs. 11.5%) (p = 0.023). In a study of overall survival (OS) in the ICI era for mRCC, we found that lung metastasis was significantly associated with improved survival compared to liver metastasis (p < 0.001: 7 months vs. 4 months). This survival advantage restricted in lung metastasis group of mRCC after adjusting age, sex, race, marital status, histological type, metastasis to bone, and brain, origin, radiotherapy record chemotherapy record, surgery on multivariable using Cox proportional hazard model (HR = 1.407; 95% CI = 1. 269−1.560; p < 0.001). The overall survival difference between the variables of the lung metastasis and liver metastasis was noted among most of the variables, with survival benefits restricted to patients in lung metastasis in the ICI era. Patients who had undergone chemotherapy and surgery were strongly positive predictors for better OS (HR = 0.427; 95% CI = 0.379−0.481; p < 0.001) (HR = 0.371; 95% CI = 0.311−0.444; p=< 0.001), and (HR = 0.313; 95% CI = 0.264−0.372; p < 0.001), (HR = 0.427; 95% CI = 0.320−0.568; p < 0.001) in lung metastasis group and liver metastasis group. The c-index of the prognostic nomogram for OS prediction was 0.74 and 0.73. This study found that patients with lung metastasis who received ICI had better survival than those with liver metastasis. Chemotherapy and surgery enhanced survival in kidney cancer patients, whereas radiation had little impact. We developed a complete and realistic nomogram for mRCC patients based on distant metastases to the lung and liver.

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Section: Discussionmentioning

confidence: 99%

A novel nomogram and prognostic factor for metastatic renal cell carcinoma survival in the era of immune checkpoint inhibitors (ICIs)

et al. 2023

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Molecular genetic and clinical characteristic analysis of primary signet ring cell carcinoma of urinary bladder identified by a novel OR2L5 mutation

et al. 2022

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To get a better understanding of the genetic basis of primary signet ring cell carcinoma (SRCC) of the bladder, which is highly rare and not yet explored. First, by using immunohistochemistry to find histological pathological characteristics.Second, a massively parallel whole-exome sequencing (WES) was performed on a 58-year-old male patient who had painless macroscopic hematuria and was pathologically diagnosed with primary SRCC of the bladder, followed by comparing with genes of ordinary urothelial cancer (UC) from TCGA. Furthermore, a population-based analysis using the SEER database was performed to investigate the prognosis (SRCC vs. UC). We identified 63 copy number variations (CNVs) with gain counts and 181 CNVs with loss counts. Totally 4515 mutations were discovered in C > T with a success rate of greater than 89%. The most frequently mutated pathway was RTK-RAS which has 85 genes involved in carcinogenic signaling. Final screening on predisposing genes is performed after filtering based on ACMG. Moreover, several driver genes, including NBN, KCTD18, SPATA13, ANKRD36, OR2L5, MALRD1, and LSMEM1, were detected. Sanger sequencing of germline DNA revealed the presence of a mutant base A/G of OR2L5 in the sequence, which was discovered for the first time in primary SRCC of the bladder. Furthermore, the immunohistochemical profile showed that primary SRCC of the bladder were positive for CK7, CK20, GATA-3, and expression of CK(AE1/ AE2), EMA, and Ki67. In the SEER-based study, the patients with primary SRCC of the bladder got a worse prognosis compared to those with UC with median months overall survival (OS) 14 vs. 41, respectively, P = 0001, even after adjusting the variables in the Cox regression model, the SRCC of the bladder showed worse survival HR = 1.119, 95% CI = (1.081-1.328), P = 0.0001. These results imply that suppression of potential driver mutations may be a viable adjuvant treatment

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Development of a Novel Pyroptosis-Associated lncRNA Biomarker Signature in Lung Adenocarcinoma

Wang

Wang²,

Castellano

et al. 2023

Mol Biotechnol

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Molecular genetic and clinical characteristic analysis of primary signet ring cell carcinoma of urinary bladder identified by a novel OR2L5 mutation

Cited by 4 publications

References 41 publications

A novel nomogram and prognostic factor for metastatic renal cell carcinoma survival in the era of immune checkpoint inhibitors (ICIs)

A novel nomogram and prognostic factor for metastatic renal cell carcinoma survival in the era of immune checkpoint inhibitors (ICIs)

Molecular genetic and clinical characteristic analysis of primary signet ring cell carcinoma of urinary bladder identified by a novel OR2L5 mutation

Development of a Novel Pyroptosis-Associated lncRNA Biomarker Signature in Lung Adenocarcinoma

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