The expression level and clinical value of ALKBH5 and PAK5 in high-risk HPV positive cervical cancer tissue

doi:10.11958/20242343

Abstract

Abstract:

Objective To analyze the expression levels of RNA demethylase alkB homolog 5 (ALKBH5) and p21 activated kinase 5 (PAK5) in high-risk human papillomavirus (HR-HPV) positive cervical cancer tissue, and explore their clinical significance. Methods A total of 96 patients with HR-HPV positive cervical cancer were selected as the research object. The expressions of ALKBH5 and PAK5 mRNA and protein in cancer tissue and adjacent tissue were analyzed by real-time fluorescent quantitative PCR, immunohistochemistry and Western blot assay. The expression levels of ALKBH5 and PAK5 proteins in patients with HR-HPV positive cervical cancer with different clinicopathological characteristics were compared. Multivariate Cox regression analysis was used to analyze influencing factors of death in patients with HR-HPV positive cervical cancer. Kaplan-Meier curve was used to analyze the effects of ALKBH5 and PAK5 protein expression on the 5-year survival rate of patients. Results The results of real-time fluorescent quantitative PCR, immunohistochemistry and Western blot assay showed that expression levels of ALKBH5 and PAK5 mRNA and protein in HR-HPV positive cervical cancer tissue were higher than those in adjacent tissue (P<0.05). The positive rates of ALKBH5 and PAK5 in cancer tissue of HR-HPV positive cervical cancer patients with FIGO stage ⅡA and lymph node metastasis were increased (P<0.05). ALKBH5 positive (HR=1.467，95%CI: 1.104-1.949), PAK5 positive (HR=1.435, 95%CI: 1.093-1.884), FIGO stage IIA (HR=1.435, 95%CI=1.065-1.933) and lymph node metastasis (HR=1.652, 95%CI: 1.053-2.593) were risk factors affecting the prognosis of HR-HPV positive cervical cancer patients (P<0.05). The 5-year cumulative survival rate was lower in the ALKBH5 positive group [72.58% (45/62) vs. 91.18% (31/34)] than that of the ALKBH5 negative group (log rank χ²=4.481, P=0.034). The 5-year overall survival rate of the PAK5 positive group [71.67% (43/60) vs. 91.67% (33/36)] was lower than that of the PAK5 negative group (log rank χ²=4.153, P=0.043). Conclusion The expression levels of ALKBH5 and PAK5 are significantly up-regulated in HR-HPV positive cervical cancer, both of which are related to the poor clinicopathological features of patients, and are helpful to evaluate the prognosis.

Key words: human papillomavirus, uterine cervical neoplasms, risk factors, prognosis, AlkB homolog 5, RNA demethylase, p21-activated kinases

CLC Number:

R737.33

Figures/Tables 5

References 19

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临床指标	n	ALKBH5阳性	χ²	PAK5阳性	χ²
年龄
<60岁	50	32（64.0）	0.016	28（56.0）	1.881
≥60岁	46	30（65.2）	0.016	32（69.6）	1.881
病理类型
鳞癌	60	35（58.3）	2.732	35（58.3）	1.185
腺癌	36	27（75.0）	2.732	25（69.4）	1.185
FIGO分期
ⅠA-ⅠB期	40	16（40.0）	18.117^＊＊	20（50.0）	4.571^＊
ⅡA期	56	46（82.1）	18.117^＊＊	40（71.4）	4.571^＊
分化程度
高中分化	44	26（59.1）	1.071	25（56.8）	1.119
低分化	52	36（69.2）	1.071	35（67.3）	1.119
肌层浸润
浅肌层	51	29（56.9）	2.835	28（54.9）	2.680
深肌层	45	33（73.3）	2.835	32（71.1）	2.680
淋巴结转移
有	37	30（81.1）	7.164^＊	32（86.5）	14.779^＊＊
无	59	32（54.2）	7.164^＊	28（47.5）	14.779^＊＊

临床指标	n	ALKBH5阳性	χ²	PAK5阳性	χ²
年龄
<60岁	50	32（64.0）	0.016	28（56.0）	1.881
≥60岁	46	30（65.2）	0.016	32（69.6）	1.881
病理类型
鳞癌	60	35（58.3）	2.732	35（58.3）	1.185
腺癌	36	27（75.0）	2.732	25（69.4）	1.185
FIGO分期
ⅠA-ⅠB期	40	16（40.0）	18.117^＊＊	20（50.0）	4.571^＊
ⅡA期	56	46（82.1）	18.117^＊＊	40（71.4）	4.571^＊
分化程度
高中分化	44	26（59.1）	1.071	25（56.8）	1.119
低分化	52	36（69.2）	1.071	35（67.3）	1.119
肌层浸润
浅肌层	51	29（56.9）	2.835	28（54.9）	2.680
深肌层	45	33（73.3）	2.835	32（71.1）	2.680
淋巴结转移
有	37	30（81.1）	7.164^＊	32（86.5）	14.779^＊＊
无	59	32（54.2）	7.164^＊	28（47.5）	14.779^＊＊

变量	β	SE	Wald χ²	P	HR	HR 95%CI
ALKBH5	0.383	0.145	6.977	0.008	1.467	1.104~1.949
PAK5	0.361	0.139	6.745	0.009	1.435	1.093~1.884
FIGO分期	0.361	0.152	5.641	0.018	1.435	1.065~1.933
淋巴结转移	0.502	0.230	4.764	0.029	1.652	1.053~2.593

变量	β	SE	Wald χ²	P	HR	HR 95%CI
ALKBH5	0.383	0.145	6.977	0.008	1.467	1.104~1.949
PAK5	0.361	0.139	6.745	0.009	1.435	1.093~1.884
FIGO分期	0.361	0.152	5.641	0.018	1.435	1.065~1.933
淋巴结转移	0.502	0.230	4.764	0.029	1.652	1.053~2.593