Sun Zhen-Qiang, Wang Hai-Jiang, Zhao Ze-Liang, Wang Qi-San, Fan Chuan-Wen, Fang Fa
Deparment of Abdomen Surgery, Affiliated Tumor Hospital, Xinjiang Medical University, Urumqi, China.
Asian Pac J Cancer Prev. 2013;14(1):121-6. doi: 10.7314/apjcp.2013.14.1.121.
Significance of HPV infection and genic mutation of APC and K-ras in rectal cancer has been investigated but not clarified. The objective of our study was to investigate these parameters in patients with rectal cancer to analyze correlations with biological behaviour, to determine relationships among the three, and also to demonstrate survival prognosis effects.
From December 2007 to September 2008, 75 rectal cancer cases confirmed by histopathology in the Tumor Hospital of Xinjiang Medical University were enrolled. The control group consisted of normal rectal mucous membrane taken simultaneously, a least 10 cm distant from the carcinoma fringe. HPV DNA, the MCR of APC and exon-1 of K-ras were detected by PCR and PCR-SSCP. All results were analyzed in relation to clinical pathological material, using chi-square and correlation analysis via SPSS.13 and Fisher's Exact Probability via STATA. 9.0. All 75 patients were followed up for survival analysis using Kaplan-Meier and Log-rank tests.
55 out of 75 cases demonstrated gene HPV L1 while it was not detected in normal rectal mucosa tissue. HPV infection was correlated with age and lymphatic metastasis (P<0.05) but not other characteristics, such as ethnicity, tumor size, histological type, tumor type, Duke's stage and infiltration depth. Some 43 cases exhibited APC genic mutation (57.3%) and 34 K-ras genic mutation (45.3%). APC genic mutation was correlated with gender( P<0.05), but not age, histological type, infiltration depth, lymphatic metastasis and Duke's stage. In 55 cases of rectal cancer with HPV infection, there were 31 cases with genic mutation of APC (56.4%) and 24 with genic mutation of K-ras (43.6%). For the 20 cases of rectal cancer with non-HPV infection, the figures were 12 cases (60%) and 10 (50.0%), respectively, with no significant relation. Survival analysis showed no statistical significance for K-ras genic mutation, APC genic mutation or HPV infection (P>0.05). However, the survival time of the patients with HPV infection was a little shorter than in cases without HPV infection.
Our results suggest that HPV infection might be an important factor to bring about malignant phenotype of rectal cancer and influence prognosis. Genic mutation of APC and K-ras might be common early molecular events of rectal cancer, but without prognostic effects on medium-term or early stage patients with rectal cancer.
人乳头瘤病毒(HPV)感染以及直肠癌中腺瘤性息肉病(APC)基因和K-ras基因突变的意义已得到研究,但尚未明确。本研究的目的是调查直肠癌患者的这些参数,分析其与生物学行为的相关性,确定三者之间的关系,并阐明其对生存预后的影响。
选取2007年12月至2008年9月在新疆医科大学肿瘤医院经组织病理学确诊的75例直肠癌患者。对照组为同时获取的距癌边缘至少10cm的正常直肠黏膜。采用聚合酶链反应(PCR)和PCR-单链构象多态性(PCR-SSCP)检测HPV DNA、APC基因的突变聚集区(MCR)和K-ras基因的第1外显子。所有结果均结合临床病理资料进行分析,使用SPSS.13软件进行卡方检验和相关性分析,使用STATA.9.0软件进行Fisher确切概率法分析。对所有75例患者进行随访,采用Kaplan-Meier法和Log-rank检验进行生存分析。
75例患者中有55例检测到HPV L1基因,而在正常直肠黏膜组织中未检测到。HPV感染与年龄和淋巴结转移相关(P<0.05),但与种族、肿瘤大小、组织学类型、肿瘤类型、杜克分期和浸润深度等其他特征无关。约43例患者出现APC基因突变(57.3%),34例出现K-ras基因突变(45.3%)。APC基因突变与性别相关(P<0.05),但与年龄、组织学类型、浸润深度、淋巴结转移和杜克分期无关。在55例HPV感染的直肠癌患者中,有31例发生APC基因突变(56.4%),24例发生K-ras基因突变(43.6%)。在20例非HPV感染的直肠癌患者中,发生APC基因突变和K-ras基因突变的分别为12例(60%)和10例(50.0%),两者无显著相关性。生存分析显示,K-ras基因突变、APC基因突变或HPV感染均无统计学意义(P>0.05)。然而,HPV感染患者的生存时间略短于未感染HPV的患者。
我们的研究结果表明,HPV感染可能是导致直肠癌恶性表型并影响预后的重要因素。APC基因和K-ras基因突变可能是直肠癌常见的早期分子事件,但对直肠癌中期或早期患者无预后影响。