Kondapuram Sree Karani, Puli Sagar, Murali Nirupama, Coumar Mohane Selvaraj
Department of Bioinformatics, School of Life Sciences, Pondicherry University, Kalapet, Puducherry, 605014, India.
Department of Pharmacology, CDSIMER, KanakapuraRoad, Ramanagara Dt, Deverakaggalahalli, Karnataka, 562 112, India.
J Mol Histol. 2025 Sep 8;56(5):303. doi: 10.1007/s10735-025-10513-4.
Survivin, an inhibitor of apoptosis protein, is minimally expressed in normal adult tissues but overexpressed in multiple cancers. This study investigates survivin expression alongside autophagy markers ATG7 and LC3B in seven solid tumor types in Indian patient samples. Immunohistochemical analysis was performed on 48 cancer tissue samples (breast n = 7, buccal n = 6, cervical n = 5, colon n = 8, renal n = 6, liver n = 10, thyroid n = 6) and adjacent normal tissues (n = 9) using anti-human antibodies against survivin, ATG7, and LC3B. Expression levels were semi-quantitatively scored (0-3 +) and statistically analyzed. Survivin demonstrated significant overexpression in cancer tissues compared to normal tissues across all tumor types (p ≤ 0.05-0.0001). Moreover, a statistically significant inverse correlation was observed between survivin and autophagy marker (ATG7/LC3B) expression in 85% of examined samples. Breast, buccal, liver, and kidney cancers showed strong-to-moderate survivin expression in > 50% of cases, while thyroid cancers exhibited predominantly weak survivin expression with strong autophagy marker expression. These findings demonstrate consistent survivin overexpression with concomitant autophagy suppression in Indian cancer patients. The inverse relationship between survivin and autophagy marker expression suggests survivin inhibition as a potential therapeutic strategy to activate autophagic cell death, particularly in breast, buccal, liver, and kidney cancers with high survivin expression. Future large-scale validation studies and mechanistic investigations are warranted to translate these findings into personalized survivin-targeted therapeutic strategies. This study contributes to a better understanding of survivin and its relation to autophagy in various solid tumors, paving the way for novel therapeutics for cancer.
生存素是一种凋亡抑制蛋白,在正常成人组织中表达极少,但在多种癌症中过度表达。本研究调查了印度患者样本中七种实体瘤类型中生存素的表达情况以及自噬标志物ATG7和LC3B的表达情况。对48个癌组织样本(乳腺癌n = 7、颊癌n = 6、宫颈癌n = 5、结肠癌n = 8、肾癌n = 6、肝癌n = 10、甲状腺癌n = 6)和相邻正常组织(n = 9)使用抗人抗生存素、ATG7和LC3B抗体进行免疫组织化学分析。对表达水平进行半定量评分(0 - 3 +)并进行统计学分析。与所有肿瘤类型的正常组织相比,生存素在癌组织中均表现出显著的过度表达(p≤0.05 - 0.0001)。此外,在85%的检测样本中,观察到生存素与自噬标志物(ATG7/LC3B)表达之间存在统计学上显著的负相关。乳腺癌、颊癌、肝癌和肾癌在超过50%的病例中表现出强至中度的生存素表达,而甲状腺癌主要表现为弱生存素表达和强自噬标志物表达。这些发现表明,在印度癌症患者中,生存素持续过度表达并伴有自噬抑制。生存素与自噬标志物表达之间的负相关关系表明,抑制生存素作为一种潜在的治疗策略,可激活自噬性细胞死亡,特别是在生存素高表达的乳腺癌、颊癌、肝癌和肾癌中。未来有必要进行大规模的验证研究和机制研究,以便将这些发现转化为个性化的靶向生存素治疗策略。本研究有助于更好地理解生存素及其在各种实体瘤中与自噬的关系,为癌症的新型治疗方法铺平道路。