Tembhurne Alok K, Maheshwari Amita, Warke Himangi, Chaudhari Hemangi, Kerkar Shilpa C, Deodhar Kedar, Rekhi Bharat, Mania-Pramanik Jayanti
ICMR-National Institute for Research in Reproductive Health, Parel, Mumbai, India.
Tata Memorial Hospital, Parel, Mumbai, India.
J Med Virol. 2023 Jan;95(1):e27873. doi: 10.1002/jmv.27873. Epub 2022 May 27.
Killer cell immunoglobulin-like receptors (KIRs) are required for natural killer cell function against virus-infected cells or tumor cells. KIR gene content polymorphisms in Indian women with cervical cancer (CaCx) remain unexplored. Hence, we analyzed the frequencies of KIR genes, KIR haplotypes, and Bx subsets to draw their association with CaCx. The polymerase chain reaction-sequence-specific primer method was used for KIR genotyping in three groups of women: healthy controls (n = 114), women with human papillomavirus (HPV) infection (n = 70), and women with CaCx (n = 120). The results showed that the frequency of KIR2DS5 was significantly higher in women with CaCx compared to women with HPV infection (p = 0.02) and healthy controls (p = 0.01). Whereas the frequency of KIR2DL5B was significantly higher in healthy controls than in women with HPV infection (p = 0.02). The total number of activating KIR genes was higher in women with CaCx than in healthy controls (p = 0.006), indicating their positive association with CaCx. Moreover, the C4T4 subset was higher in women with CaCx than in women with HPV infection, though not significant. In conclusion, our findings highlight KIR2DS5, the C4T4 subset, and activating KIR genes are susceptible factors or positively associated with CaCx. Besides KIR2DL5B, this study also reported for the first time significantly high frequency of KIR2DL1 in healthy controls, indicating its possible protective association against CaCx. Further, significantly high frequency of KIR2DL3 observed in HPV-infected women might be also a promising biomarker for viral infections. Thus, the study confirms the association of KIR genes with cervical cancer in women with HPV infection.
杀伤细胞免疫球蛋白样受体（KIRs）是自然杀伤细胞针对病毒感染细胞或肿瘤细胞发挥功能所必需的。印度宫颈癌（CaCx）女性中KIR基因含量多态性尚未得到研究。因此，我们分析了KIR基因、KIR单倍型和Bx亚群的频率，以确定它们与CaCx的关联。采用聚合酶链反应-序列特异性引物方法对三组女性进行KIR基因分型：健康对照者（n = 114）、人乳头瘤病毒（HPV）感染女性（n = 70）和CaCx女性（n = 120）。结果显示，与HPV感染女性（p = 0.02）和健康对照者（p = 0.01）相比，CaCx女性中KIR2DS5的频率显著更高。而健康对照者中KIR2DL5B的频率显著高于HPV感染女性（p = 0.02）。CaCx女性中激活型KIR基因的总数高于健康对照者（p = 0.006），表明它们与CaCx呈正相关。此外，CaCx女性中的C4T4亚群高于HPV感染女性，尽管差异不显著。总之，我们的研究结果表明，KIR2DS5、C4T4亚群和激活型KIR基因是CaCx的易感因素或与CaCx呈正相关。除了KIR2DL5B，本研究还首次报道了健康对照者中KIR2DL1的频率显著较高，表明其可能与CaCx存在保护性关联。此外，在HPV感染女性中观察到的KIR2DL3频率显著较高也可能是病毒感染的一个有前景的生物标志物。因此，该研究证实了KIR基因与HPV感染女性宫颈癌的关联。
