Integrating HECW1 expression into the clinical indicators exhibits high accuracy in assessing the prognosis of patients with clear cell renal cell carcinoma.
BACKGROUND
Although many intratumoral biomarkers have been reported to predict clear cell renal cell carcinoma (ccRCC) patient prognosis, combining intratumoral and clinical indicators could predict ccRCC prognosis more accurately than any of these markers alone. This study mainly examined the prognostic value of HECT, C2 and WW domain-containing E3 ubiquitin protein ligase 1 (HECW1) expression in ccRCC patients in combination with established clinical indicators.


METHODS
The expression level of HECW1 was screened out by data-independent acquisition mass spectrometry (DIA-MS) and analyzed in ccRCC patients from the The Cancer Genome Atlas (TCGA) database and our cohort. A total of 300 ccRCC patients were stochastically divided into a training cohort and a validation cohort, and real-time PCR, immunohistochemistry (IHC) and statistical analyses were employed to examine the prognostic value of HECW1 in ccRCC patients.


RESULTS
The expression level of HECW1 usually decreased in human ccRCC specimens relative to control specimens in TCGA (p < 0.001). DIA-MS, Real-time PCR, and IHC analyses also showed that the majority of ccRCCs harbored decreased HECW1 expression compared with that in normal adjacent tissues (p < 0.001). Additionally, HECW1 expression was reduced in ccRCC cell lines compared with the normal renal cell line HK-2 (p < 0.001). Moreover, lower HECW1 expression was found in ccRCC patients with a higher tumor node metastasis (TNM) stage, bone metastasis, or first-line targeted drug resistance (p < 0.001). Low HECW1 expression indicated higher TNM stage, SSIGN (Stage, Size, Grade, and Necrosis) score and WHO/ISUP grade and poor prognosis in ccRCC patients (p < 0.05). Even after multivariable adjustment, HECW1, TNM stage, and SSIGN score served as independent risk factors. The c-index analysis showed that integrating intratumoral HECW1 expression into TNM stage or SSIGN score resulted in a higher c-index value than these indicators alone for predicting ccRCC patient prognosis.


CONCLUSION
HECW1 is a novel prognostic biomarker and therapeutic target in ccRCC, and integrating intratumoral HECW1 expression with established clinical indicators yields higher accuracy in assessing the postoperative prognosis of ccRCC patients.
['Wang|Chao|C|', 'Dong|Keqin|K|', 'Wang|Yuning|Y|', 'Peng|Guang|G|', 'Song|Xu|X|', 'Yu|Yongwei|Y|', 'Shen|Pei|P|', 'Cui|Xingang|X|']
D000293:Adolescent D000328:Adult D000368:Aged D000369:Aged, 80 and over D014408:Biomarkers, Tumor D002292:Carcinoma, Renal Cell D030541:Databases, Genetic D005260:Female D015870:Gene Expression D006801:Humans D007150:Immunohistochemistry D007680:Kidney Neoplasms D008297:Male D008875:Middle Aged D009367:Neoplasm Staging D009419:Nerve Tissue Proteins D011379:Prognosis D044767:Ubiquitin-Protein Ligases D055815:Young Adult
HECW1 Clear cell renal cell carcinoma Disease progression Prognostic marker